MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

Researchers from the ‘International Centre for Allied Health Evidence’, University of South Australia in Adelaide wanted to determine whether massage therapy is an effective intervention for back pain. They carried out extensive literature searches to identify all systematic reviews on the subject, analysed them critically and evaluated their methodological quality. Nine systematic reviews were found. Their methodological quality varied from poor to excellent. The primary research informing these systematic reviews was generally considered to be weak quality. The findings indicated that massage may be an effective treatment option when compared to placebo or active treatment options such as relaxation, especially in the short term. There were conflicting and contradictory findings for the effectiveness of massage therapy as a treatment of non-specific low back pain when compared against other manual therapies such as mobilization, standard medical care, and acupuncture.

The authors concluded that there is an emerging body of evidence, albeit small, that supports the effectiveness of massage therapy for the treatment of non-specific low back pain in the short term. Due to common methodological flaws in the primary research, which informed the systematic reviews recommendations arising from this evidence base should be interpreted with caution.

My own systematic review from 1999 (which the authors of this systematic review of systematic reviews seem to have missed) concluded that massage seems to have some potential as a therapy for low back pain. Indeed, there seems to be unanimous agreement that massage therapy is a promising treatment. Why then do massage therapists not finally get their act together and conduct a few more high quality primary studies? Currently, we have about as many reviews as trials! Doing even more reviews will not answer the question about effectiveness!!!

And it is a damn important question. Back pain is extremely common and extremely expensive for us all. At present, we have no optimal treatment. Chiropractors and osteopaths are claiming to have found a good solution, but many experts are not convinced by their evidence and argue that the risks of spinal manipulation might not outweigh its benefits. Massage, by contrast, is almost risk-free. Considering all this, I believe we need more trials with some urgency.

So, why are such trials not forthcoming? I realise that multiple hurdles have to be taken:

  • Clinical studies of that nature are expensive, and there is no obvious funding source.
  • Massage therapists usually do not have enough research expertise to pull off a sound study.
  • There are multiple methodological problems in conduction a definitive massage trial that might convince us all.

However, none of these obstacles are insurmountable. I suggest massage therapists team up with experts who know how to run clinical trials, hammer out a reasonable study design and approach government or other official funders for support. We need a definitive answers and we need them soon: is massage effective? which type of massage? for which patients? at which stage of non-specific low back pain?

Can one design a clinical study in such a way that it looks highly scientific but, at the same time, has zero chances of generating a finding that the investigators do not want? In other words, can one create false positive findings at will and get away with it? I think it is possible; what is more, I believe that, in alternative medicine, this sort of thing happens all the time. Let me show you how it is done; four main points usually suffice:

  1.  The first rule is that it ought to be an RCT, if not, critics will say the result was due to selection bias. Only RCTs have the reputation of being ‘top notch’.
  2.  Once we are clear about this design feature, we need to define the patient population. Here the trick is to select individuals with an illness that cannot be quantified objectively. Depression, stress, fatigue…the choice is vast. The aim must be to employ an outcome measure that is well-accepted, validated etc. but which nevertheless is entirely subjective.
  3.  Now we need to consider the treatment to be “tested” in our study. Obviously we take the one we are fond of and want to “prove”. It helps tremendously, if this intervention has an exotic name and involves some exotic activity; this raises our patients’ expectations which will affect the result. And it is important that the treatment is a pleasant experience; patients must like it. Finally it should involve not just one but several sessions in which the patient can be persuaded that our treatment is the best thing since sliced bread – even if, in fact, it is entirely bogus.
  4.  We also need to make sure that, for our particular therapy, no universally accepted placebo exists which would allow patient-blinding. That would be fairly disastrous. And we certainly do not want to be innovative and create such a placebo either; we just pretend that controlling for placebo-effects is impossible or undesirable. By far the best solution would be to give the control group no treatment at all. Like this, they are bound to be disappointed for missing out a pleasant experience which, in turn, will contribute to unfavourable outcomes in the control group. This little trick will, of course, make the results in the experimental group look even better.

That’s about it! No matter how ineffective our treatment is, there is no conceivable way our study can generate a negative result; we are in the pink!

Now we only need to run the trial and publish the positive results. It might be advisable to recruit several co-authors for the publication – that looks more serious and is not too difficult: people are only too keen to prolong their publication-list. And we might want to publish our study in one of the many CAM-journals that are not too critical, as long as the result is positive.

Once our article is in print, we can legitimately claim that our bogus treatment is evidence-based. With a bit of luck, other research groups will proceed in the same way and soon we will have not just one but several positive studies. If not, we need to do two or three more trials along the same lines. The aim is to eventually do a meta-analysis that yields a convincingly positive verdict on our phony intervention.

You might think that I am exaggerating beyond measure. Perhaps a bit, I admit, but I am not all that far from the truth, believe me. You want proof? What about this one?

Researchers from the Charite in Berlin just published an RCT to investigate the effectiveness of a mindful walking program in patients with high levels of perceived psychological distress.

To prevent allegations of exaggeration, selective reporting, spin etc. I take the liberty of reproducing the abstract of this study unaltered:

Participants aged between 18 and 65 years with moderate to high levels of perceived psychological distress were randomized to 8 sessions of mindful walking in 4 weeks (each 40 minutes walking, 10 minutes mindful walking, 10 minutes discussion) or to no study intervention (waiting group). Primary outcome parameter was the difference to baseline on Cohen’s Perceived Stress Scale (CPSS) after 4 weeks between intervention and control.

Seventy-four participants were randomized in the study; 36 (32 female, 52.3 ± 8.6 years) were allocated to the intervention and 38 (35 female, 49.5 ± 8.8 years) to the control group. Adjusted CPSS differences after 4 weeks were -8.8 [95% CI: -10.8; -6.8] (mean 24.2 [22.2; 26.2]) in the intervention group and -1.0 [-2.9; 0.9] (mean 32.0 [30.1; 33.9]) in the control group, resulting in a highly significant group difference (P < 0.001).

Conclusion. Patients participating in a mindful walking program showed reduced psychological stress symptoms and improved quality of life compared to no study intervention. Further studies should include an active treatment group and a long-term follow-up

This whole thing could just be a bit of innocent fun, but I am afraid it is neither innocent nor fun, it is, in fact, quite serious. If we accept manipulated trials as evidence, we do a disservice to science, medicine and, most importantly, to patients. If the result of a trial is knowable before the study has even started, it is unethical to run the study. If the trial is not a true test but a simple promotional exercise, research degenerates into a farcical pseudo-science. If we abuse our patients’ willingness to participate in research, we jeopardise more serious investigations for the benefit of us all. If we misuse the scarce funds available for research, we will not have the money to conduct much needed investigations. If we tarnish the reputation of clinical research, we hinder progress.

Swiss chiropractors have just published a clinical trial to investigate outcomes of patients with radiculopathy due to cervical disk herniation (CDH). All patients had neck pain and dermatomal arm pain; sensory, motor, or reflex changes corresponding to the involved nerve root and at least one positive orthopaedic test for cervical radiculopathy were included. CDH was confirmed by magnetic resonance imaging. All patients received regular neck manipulations.

Baseline data included two pain numeric rating scales (NRSs), for neck and arm, and the Neck Disability Index (NDI). At two, four and twelve weeks after the initial consultation, patients were contacted by telephone, and the data for NDI, NRSs, and patient’s global impression of change were collected. High-velocity, low-amplitude thrusts were administered by experienced chiropractors. The proportion of patients reporting to feel “better” or “much better” on the patient’s global impression of change scale was calculated. Pre-treatment and post-treatment NRSs and NDIs were analysed.

Fifty patients were included. At two weeks, 55.3% were “improved,” 68.9% at four and 85.7% at twelve weeks. Statistically significant decreases in neck pain, arm pain, and NDI scores were noted at 1 and 3 months compared with baseline scores. 76.2% of all sub-acute/chronic patients were improved at 3 months.

The authors concluded that most patients in this study, including sub-acute/chronic patients, with symptomatic magnetic resonance imaging-confirmed CDH treated with spinal manipulative therapy, reported significant improvement with no adverse events.

In the presence of disc herniation, chiropractic manipulations have been described to cause serious complications. Some experts therefore believe that CDH is a contra-indication for spinal manipulation. The authors of this study imply, however, that it is not – on the contrary, they think it is an effective intervention for CDH.

One does not need to be a sceptic to notice that the basis for this assumption is less than solid. The study had no control group. This means that the observed effect could have been due to:

a placebo response,

the regression towards the mean,

the natural history of the condition,

concomitant treatments,

social desirability,

or other factors which have nothing to do with the chiropractic intervention per se.

And what about the interesting finding that no adverse-effects were noted? Does that mean that the treatment is safe? Sorry, but it most certainly does not! In order to generate reliable results about possibly rare complications, the study would have needed to include not 50 but well over 50 000 patients.

So what does the study really tell us? I have pondered over this question for some time and arrived at the following answer: NOTHING!

Is that a bit harsh? Well, perhaps yes. And I will revise my verdict slightly: the study does tell us something, after all – chiropractors tend to confuse research with the promotion of very doubtful concepts at the expense of their patients. I think, there is a name for this phenomenon: PSEUDO-SCIENCE.

Researchers from the ‘Complementary and Integrative Medicine Research, Primary Medical Care, University of Southampton’ conducted a study of Professional Kinesiology Practice (PKP) What? Yes, PKP! This is a not widely known alternative method.

According to its proponents, it is unique and a complete kinesiology system… It was developed by a medical doctor, Dr Bruce Dewe and his wife Joan Dewe in the 1980s and has been taught since then in over 16 countries around the world with great success… Kinesiology is a unique and truly holistic science and on the cutting edge of energy medicine. It uses muscle monitoring as a biofeedback system to identify the underlying cause of blockage from the person’s subconscious mind via the nervous system. Muscle monitoring is used to access information from the person’s “biocomputer”, the brain, in relation to the problem or issue and also guides the practitioner to find the priority correction in order to stimulate the person’s innate healing capacity and support their physiology to return to normal function. Kinesiology is unique as it looks beyond symptoms. It recognizes the flows of energy within the body not only relate to the muscles but to every tissue and organ that make the human body a living ever changing organism. These energy flows can be evaluated by testing the function of the muscles, which in turn reflect the body’s overall state of structural, chemical, emotional and spiritual balance. In this way kinesiology taps into energies that the more conventional modalities overlook and helps remove all the guesswork, doubt and hard work of subjective diagnostics. This is a revolutionary way to communicate with the body/mind connection. Through muscle monitoring and the use of over 300 fingermodes we can detect and correct the cause of the problem and effect a long lasting change for better health and wellbeing. Our posture could be considered to be the visual display unit from our internal bio-computer. Our posture / life energy improves as we upgrade the way we respond to life’s constant challenges and demands.

You do not understand? Let me make it crystal clear by citing another PKP-site:

PKP is a phenomenological practice – this means practitioners use manual muscle testing to demonstrate to the client how much or how little they are able to move in relation to their problem. PKP practitioners have tests for more than 100 muscles, and dozens of other tests that they do so they can clearly show you how your movement is affected by your problem. This muscle story shows a person how their life is unfolding, and it also helps to guide on how to transcend the situation and design a future which is more in alignment with nature and the laws of the cosmos… PKP is about living life more wisely.

In case you still have not understood what PKP is, you might have to watch this youtube clip. And now that everyone knows what it is, let us have a look at the new study.

According to its authors, it was an exploratory, pragmatic single-blind, 3-arm randomised sham-controlled pilot trial with waiting list control (WLC) which was conducted in the setting of a UK private practice. Seventy participants scoring ≥4 on the Roland and Morris Disability Questionnaire (RMDQ) were randomised to real or sham PKP receiving one treatment weekly for 5 weeks or a WLC. WLC’s were re-randomised to real or sham after 6 weeks. The main outcome measure was a change in RMDQ from baseline to end of 5 weeks of real or sham PKP.

The results show an effect size of 0.7 for real PKP which was significantly different to sham. Compared to WLC, both real and sham groups had significant RMDQ improvements. Practitioner empathy (CARE) and patient enablement (PEI) did not predict outcome; holistic health beliefs (CAMBI) did, though. The sham treatment appeared credible; patients did not guess treatment allocation. Three patients reported minor adverse reactions.

From these data, the authors conclude that real treatment was significantly different from sham demonstrating a moderate specific effect of PKP; both were better than WLC indicating a substantial non-specific and contextual treatment effect. A larger definitive study would be appropriate with nested qualitative work to help understand the mechanisms involved in PKP.

So, PKP has a small specific effect in addition to generating a sizable placebo-effect? Somehow, I doubt it! This was, according to its authors, a pilot study. Such an investigation should not evaluate the effectiveness of a treatment but the feasibility of the protocol. Even if we disregard this detail, I assume that the results indicate the effects of PKP to be essentially due to placebo. The small effect which the authors label as “specific” is, in my view, almost certainly caused by residual confounding and hidden biases.

One could also go one step further and say that any treatment that is shrouded in pseudo-scientific language and has zero plausibility is an ill-conceived candidate for a clinical trial of this nature. If it should be tested at all – and thus cost money, effort and patient-participation – a rigorous study should be designed and conducted not by apologists of the intervention but by more level-headed scientists.

Massage is an agreeable and pleasant treatment. It comes in various guises and, according to many patients’ experience, it relaxes both the mind and the body. But does it have therapeutic effects which go beyond such alleged benefits?

There is a considerable amount of research to test whether massage is effective for some conditions, including depression. In most instances, the evidence fails to be entirely convincing. Our own systematic review of massage for depression, for instance, concluded that there is currently a lack of evidence.

This was ~5 years ago – but now a new trial has emerged. It was aimed at determining whether massage therapy reduces symptoms of depression in subjects with human immunodeficiency virus (HIV) disease. Subjects were randomized into one of three groups to receive either Swedish massage (the type that is best researched amongst the many massage-variations that exist), or touch, or no such interventions. The treatment period lasted for eight weeks. Patients had to be at least 16 years of age, HIV-positive, suffering from a major depressive disorder, and on a stable neuropsychiatric, analgesic, and antiretroviral regimen for > 30 days with no plans to modify therapy for the duration of the study. Approximately 40% of the subjects were taking antidepressants, and all subjects were judged to be medically stable.

Patients in the Swedish massage and touch groups visited the massage therapist for one hour twice per week. In the touch group, a massage therapist placed both hands on the subject with slight pressure, but no massage, in a uniform distribution in the same pattern used for the massage subjects.

The primary and secondary outcome measures were the Hamilton Rating Scale for Depression score and the Beck Depression Inventory. The results showed that, compared to no intervention and/or touch, massage significantly reduced the severity of depression at week 4, 6 and 8.

The authors’ conclusion is clear: The results indicate that massage therapy can reduce symptoms of depression in subjects with HIV disease. The durability of the response, optimal “dose” of massage, and mechanisms by which massage exerts its antidepressant effects remain to be determined.

Clinical trials of massage therapy encounter formidable problems. No obvious funding source exists, and the expertise to conduct research is minimal within the realm of massage therapy. More importantly, it is difficult to find solutions to the many methodological issues involved in designing rigorous trials of massage therapy.

One such issue is the question of an adequate control intervention which might enable to blind patients and thus account for the effects of placebo, compassion, attention etc. The authors of the present trial have elegantly solved it by creating a type of sham treatment which consisted of mere touch. However, this will only work well, if patients can be made to believe that the sham-intervention was a real treatment, and if somehow the massage therapist is prevented to influence the patients through verbal or non-verbal communications. In the current trial, patients were not blinded, and therefore patients’ expectations may have played a role in influencing the results.

Despite this drawback, the study is one of the more rigorous investigations of massage therapy to date. Its findings offer hope to those patients who suffer from depression and who are desperate for an effective and foremost safe treatment to ease their symptoms.

My conclusion: the question whether massage alleviates depression is intriguing and well worth further study.

Rudolf Steiner was a weird guy by any stretch of imagination. He was the founding father of anthroposophy, an esoteric “philosophy” that created a new dimension of obtrusiveness. Not only that, he also dabbled in farming methods, devised an educational technique and created an entire school of health care, called anthroposophical medicine. The leading product in its range of homeopathy-inspired “drugs” is a mistletoe-extract which is, according to Steiner, a cure for cancer. His idea was simple: the mistletoe plant is a parasite that lives off host trees sapping its resources until, eventually, it might even kill its host – just like cancer threatening the life of a human being!!!

So, what is more logical than to postulate that extracts from mistletoe are a cure for cancer? Medicine seems simple – particularly, if  you do not understand the first thing about it!

But here comes the odd thing: some ingredients from mistletoe do actually have anti-cancer properties. So, was the old Steiner an intuitive genius who somehow sensed that mistletoe would be a life-saver for cancer patients? Or is all this just pure luck? Or was it perhaps predictable?

Many plants produce molecules that are so toxic that they can kill (cancer) cells, and many conventional cancer drugs were originally derived from plants; the fact that mistletoe has some anti-cancer activity therefore comes as a surprise only to those who have little or no knowledge of phyto-pharmacology.

Ok, mistletoe might have some ingredients which possess pharmacological activity. But to claim that it is a cancer cure is still a huge leap of faith. This fact did not stop promoters of anthroposophical medicine to do just that.

Due to decades of clever promotion, it is now hard in many countries (including for instance Germany) to find cancer patients who have not tried mistletoe; indeed, selling mistletoe preparations to desperate cancer patients has become a mega-business.

But does it actually work?  Do these extracts achieve what proponents advertise?

The claims for mistletoe are essentially twofold:

1) Mistletoe cures cancer.

2) Mistletoe improves the quality of life (QoL) of cancer patients.

The crucial question clearly is: are these claims based on good evidence?

According to our own systematic review, the answer is NO. In 2003, we looked at all the clinical trials and demonstrated that some of the weaker studies implied benefits of mistletoe extracts, particularly in terms of quality of life. None of the methodologically stronger trials exhibited efficacy in terms of quality of life, survival or other outcome measures. The current Cochrane review (of which I am not a co-author) concluded similarly : The evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak.

But both reviews have one major weakness: they included all of the many available extracts of mistletoe – and one cannot deny that there are considerable differences between them. The market leader in this area is Weleda (avid readers of science blogs might remember that this firm has been mentioned before); they produce ISCADOR, the mistletoe extract that has been tested more than any other such preparation.

Perhaps it would be informative to focus specifically on this product then? A German team from the “Center for Integrative Medicine, Faculty of Health, University of Witten/Herdecke” has done just that; despite the fact that these authors are not really known for their critical analyses of anthroposophical medicine, their conclusion is also cautious: The analyzed studies give some evidence that Iscador treatment might have beneficial short-time effects on QoL-associated dimensions and psychosomatic self-regulation.

So, what is the bottom line? Sceptics would say that almost a century of research without a solid proof of efficacy is well and truly enough; one should now call it a day. Proponents of mistletoe treatment, however, insist: we need more and better studies. Well, there is more! A new RCT of Iscador has just been published.

It included chemotherapy-naive advanced non-small-cell lung cancer (NSCLC) patients to assess Iscador’s influence on chemotherapy-related adverse-effects and QoL. Patients with advanced NSCLC were randomised to receive chemotherapy alone or chemotherapy plus Iscador thrice weekly until tumour progression. Chemotherapy consisted of 21-day cycles of carboplatin combined with gemcitabine or pemetrexed. Seventy-two patients were enrolled of whom 65% were in stage IV, and 62% had squamous histology. Median overall survival in both groups was 11 months. Median time to tumour progression was not significantly different between the two groups. Differences in grade 3-4 haematological toxicity were not significant, but more control patients had chemotherapy dose reductions, grade 3-4 non-haematological toxicities, and hospitalisations.

The authors’ conclusion: No effect of Iscador could be found on quality of life or total adverse events. Nevertheless, chemotherapy dose reductions, severe non-haematological side-effects and hospitalisations were less frequent in patients treated with Iscador, warranting further investigation of Iscador as a modifier of chemotherapy-related toxicity.

So, does Steiner’s notion based on the weirdest of intuitions contain some kernel of truth? I am not sure. But for once I do agree with the proponents of mistletoe: we need more and better research to find out.

It hardly is a secret: we have a growing problem with obesity. Worldwide it is predicted to cause millions of premature deaths – unless, of course, we come up with a safe and effective treatment that patients find acceptable.

Many herbal remedies are being promoted as the solution to this serious problem. My team looked at the evidence for such treatments in much detail. Sadly the results were less than impressive.

But now, there seems to be new hope! Two recent studies of a specific herbal mixture report amazingly good results – or are they perhaps too good to be true?

Stern JS, Peerson J, Mishra AT, Sadasiva Rao MV and Rajeswari KP from the Department of Nutrition and the Department of Internal Medicine, University of California Davis, have just published an RCT in 60 subjects with body mass index (BMI) between 30 and 40 kg/square meter. Participants received either 400 mg herbal capsules with extracts from Sphaeranthus indicus and Garcinia mangostana or 400 mg placebo capsules twice daily. During the study period, participants consumed a standard diet (2,000 kcal per day) and walked 30 min 5 days per week.

After 8 weeks of this treatment, significant reductions in body weight (3.7 kg), BMI (1.6 kg/m2), and waist circumference (5.4 cm) were observed in the herbal group compared with placebo. Additionally, a significant increase in serum adiponectin concentration was found in the herbal group versus placebo. Adverse events were mild and were equally distributed between the two groups.

The authors’ conclusion leave no doubt: Supplementation with the herbal blend resulted in a greater degree of weight loss than placebo over 8 weeks.

As our own review had suggested that extracts of Garcinia cause small short-term weight reductions, the results did not come as a complete surprise to me. What did strike me as odd, however, was the fact that almost simultaneously another article was published. It was authored by Stern JS, Peerson J, Mishra AT, Mathukumalli VS and Konda PR from the Department of Nutrition, University of California-Davis, and it reported the pooled data from the above plus another, similarly designed trial.

The two studies together enrolled 100 patients who were treated either with the same herbal formula or with placebo. All subjects received 2000 kcal/day throughout the study and walked 5 days a week for 30 min. The primary outcome was the reduction in body weight. Secondary outcomes were reductions in BMI and in waist and hip circumference. Serum glycaemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and the data from these two studies were pooled and analysed.

At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg), BMI (2.2 kg/m2), as well as waist (11.9 cm) and hip circumferences (6.3 cm) were observed in the pooled herbal groups compared with placebo. A significant increase in serum adiponectin concentration was also found in the herbal groups versus placebo at study conclusion along with reductions in fasting blood glucose (12.2%), cholesterol (13.8%), and triglyceride (41.6%) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups.

And what should be odd about that? Authors are entitled to pool the data of two of their own trials! Yes, of course, but what confuses me is the fact that the data from the second study of 40 patients cannot be found anywhere. I would have liked to see how it is possible that the results from just 40 more patients (actually just 35 seemed to have been included in the analysis) raise the average weight loss from 3.7 kg in the first RCT to a remarkable 5.2 kg in the two RCTs together. As a rough estimate, this means that, in the second trial, patients who took the herbal mixture must have lost about one kilo per week more than those who were on placebo. If true, this outcome is pretty sensational! It could signal the end of the obesity epidemic. It would also mean that the manufacturer of this herbal wonder mixture stands to earn billions.

Considering the potential importance of these findings, I would also like to know what precisely the Californian researchers’ involvement has been in these two studies. In the second article they state that: The two clinical trials were performed at Alluri Sitarama Raju Academy of Medical Sciences (ASRAM), Eluru, Andhra Pradesh, India from November 2009 to April 2010 (clinical trial registration number: ISRCTN45078827) and from March 2010 to July 2010 (clinical trial registration number: ISRCTN52261953). I find this puzzling.

Moreover, it would be interesting to learn what happened to the following co-authors of the first study: Sadasiva, Rao MV and Rajeswari KP. As authors of the largest of the two trials, I would have thought their names would have to be included in the article reporting the pooled data of the two studies.

Call me sceptical, perhaps even cynical, but I do wonder about trials which seem to beg so many intriguing questions. In case you want to know who funded these studies and who thus stands to make the above-named billions, the answer is provided in the second paper: This work was supported by an unrestricted grant from InterHealth Nutraceuticals Inc., Benicia, CA, to J.S.S.

So, do I think that we have finally identified a safe and effective treatment to combat the worldwide epidemic of obesity? Well….

Did I previously imply that osteopaths are not very research-active? Shame on me!

Here are two brand-new studies by osteopaths and they both seem to show that their treatments work.

Impressed?

Well, perhaps we better have a closer look at them before we start praising osteopathic research efforts.

THE FIRST STUDY

Researchers from the ‘European Institute for Evidence Based Osteopathic Medicine’ in Chieti, Italy, investigated the effect of  osteopathic manipulative therapy (OMT) on the length of hospital-stay (LOHS) in premature infants. They conducted an RCT on 110 preterm newborns admitted to a single specialised unit. Thus the subjects with a gestational age between 28 and 38 weeks were randomized to receive either just routine care, or routine care with OMT for the period of hospitalization. Endpoints were differences in LOHS and daily weight gain. The results showed a mean difference in LOHS between the OMT and the control group: -5.906 days (95% C.I. -7.944, -3.869; p<0.001). However, OMT was not associated with any change in daily weight gain.

The authors’ conclusion was bold: OMT may have an important role in the management of preterm infants hospitalization.

THE SECOND STUDY

The second investigation suggested similarly positive effects of OMT on LOHS in a different setting. Using a retrospective cohort study, US osteopaths wanted to determine whether there is a relationship between post-operative use of OMT and post-operative outcomes in gastrointestinal surgical patients, including time to flatus, clear liquid diet, and bowel movement [all indicators for the length of the post-operative ileus] as well as LOHS. They thus assessed the records of 55 patients who underwent a major gastrointestinal operation in a hospital that had been routinely offering OMT to its patients. The analyses showed that 17 patients had received post-operative OMT and 38 had not.The two groups were similar in terms of all variables the researchers managed to assess. The time to bowel movement and to clear liquid diet did not differ significantly between the groups. The mean time to flatus was 4.7 days in the non-OMT group and 3.1 days in the OMT group (P=.035). The mean post-operative hospital LOHS was also reduced significantly with OMT, from 11.5 days in the non-OMT group to 6.1 days in the OMT group (P=.006).

The authors concluded that OMT applied after a major gastrointestinal operation is associated with decreased time to flatus and decreased postoperative hospital LOHS.

WHAT SHOULD WE MAKE OF THESE RESULTS?

Some people may have assumed that OMT is for bad backs; these two studies imply, however, that it can do much more. If the findings are correct, they have considerable implications: shortening the time patients have to spend in hospital would not only decrease individual suffering, it would also save us all tons of money! But do these results hold water?

The devil’s advocate in me cannot help but being more than a little sceptical. I fail to see how OMT might shorten LOHS; it just does not seem plausible! Moreover, some of the results seem too good to be true. Could there be any alternative explanations for the observed findings?

The first study, I think, might merely demonstrate that more time spent handling  premature babies provides a powerful developmental stimulus. Therefore the infants are quicker ready to leave hospital compared to those children who did not receive this additional boost. But the effect might not at all be related to OMT per se; if, for instance, the parents had handled their children for the same amount of time, the outcome would probably have been quite similar, possibly even better.

The second study is not an RCT and therefore it tells us little about cause and effect. We might speculate, for instance, that those patients who elected to have OMT were more active, had lived healthier lives, adhered more rigorously to a pre-operative diet, or differed in other variables from those patients who chose not to bother with OMT. Again, the observed difference in the duration of the post-operative ileus and consequently the LOHS would be entirely unrelated to OMT.

I suggest therefore to treat these two studies with more than just a pinch of salt. Before hospitals all over the world start employing osteopaths right, left and centre in order to shorten their average LOHS, we might be well advised to plan and conduct a trial that avoids the pitfalls of the research so far. I would bet a fiver that, once we do a proper independent replication, we will find that both investigations did, in fact, generate false positive results.

My conclusion from all this is simple: RESEARCH CAN SOMETIMES BE MISLEADING, AND POOR QUALITY RESEARCH IS ALMOST INVARIABLY MISLEADING.

A recently published study by Danish researchers aimed at comparing the effectiveness of a patient education (PEP) programme with or without the added effect of chiropractic manual therapy (MT) to a minimal control intervention (MCI). Its results seem to indicate that chiropractic MT is effective. Is this the result chiropractors have been waiting for?

To answer this question, we need to look at the trial and its methodology in more detail.

A total of 118 patients with clinical and radiographic unilateral hip osteoarthritis (OA) were randomized into one of three groups: PEP, PEP+ MT or MCI. The PEP was taught by a physiotherapist in 5 sessions. The MT was delivered by a chiropractor in 12 sessions, and the MCI included a home stretching programme. The primary outcome measure was the self-reported pain severity on an 11-box numeric rating scale immediately following the 6-week intervention period. Patients were subsequently followed for one year.

The primary analyses included 111 patients. In the PEP+MT group, a statistically and clinically significant reduction in pain severity of 1.9 points was noted compared to the MCI of 1.90. The number needed to treat for PEP+MT was 3. No difference was found between the PEP and the MCI groups. At 12 months, the difference favouring PEP+MT was maintained.

The authors conclude that for primary care patients with osteoarthritis of the hip, a combined intervention of manual therapy and patient education was more effective than a minimal control intervention. Patient education alone was not superior to the minimal control intervention.

This is an interesting, pragmatic trial with a result suggesting that chiropractic MT in combination with PEP is effective in reducing the pain of hip OA. One could easily argue about the small sample size, the need for independent replication etc. However, my main concern is the fact that the findings can be interpreted in not just one but in at least two very different ways.

The obvious explanation would be that chiropractic MT is effective. I am sure that chiropractors would be delighted with this conclusion. But how sure can we be that it would reflect the truth?

I think an alternative explanation is just as (possibly more) plausible: the added time, attention and encouragement provided by the chiropractor (who must have been aware what was at stake and hence highly motivated) was the effective element in the MT-intervention, while the MT per se made little or no difference. The PEP+MT group had no less than 12 sessions with the chiropractor. We can assume that this additional care, compassion, empathy, time, encouragement etc. was a crucial factor in making these patients feel better and in convincing them to adhere more closely to the instructions of the PEP. I speculate that these factors were more important than the actual MT itself in determining the outcome.

In my view, such critical considerations regarding the trial methodology are much more than an exercise in splitting hair. They are important in at least two ways.

Firstly, they remind us that clinical trials, whenever possible, should be designed such that they allow only one interpretation of their results. This can sometimes be a problem with pragmatic trials of this nature. It would be wise, I think, to conduct pragmatic trials only of interventions which have previously been proven to work.  To the best of my knowledge, chiropractic MT as a treatment for hip OA does not belong to this category.

Secondly, it seems crucial to be aware of such methodological issues and to consider them carefully before research findings are translated into clinical practice. If not, we might end up with  therapeutic decisions (or guidelines) which are quite simply not warranted.

I would not be in the least surprised, if chiropractic interest groups were to use the current findings for promoting chiropractic in hip-OA. But what, if the MT per se was ineffective, while the additional care, compassion and encouragement was? In this case, we would not need to recruit (and pay for) chiropractors and put up with the considerable risks chiropractic treatments can entail; we would merely need to modify the PE programme such that patients are better motivated to adhere to it.

As it stands, the new study does not tell us much that is of any practical use. In my view, it is a pragmatic trial which cannot readily be translated into evidence-based practice. It might get interpreted as good news for chiropractic but, in fact, it is not.

Acupuncture is not just one single form of therapy, there are dozens of variations of this theme. For instance, acupuncture-points can, according to proponents of this form of treatment, be stimulated in a number of ways: needles, heat (moxibustion), electrical current, laser-light, ultrasound or pressure. In the latter case, the therapy is called acupressure. This therapy is popular and often recommended as a form of self-treatment, for instance, to alleviate nausea and vomiting of all causes.

Chemotherapy-induced nausea/vomiting can normally be successfully treated with standard anti-emetic drugs. Some patients, however, may not respond satisfactorily and others prefer a drug-free option such as acupressure for which there has been encouraging evidence. A brand-new study sheds new light on this issue.

Its objective was to assess the effectiveness and cost-effectiveness of self-administered acupressure using wristbands compared with sham acupressure wristbands and standard care alone in the management of chemotherapy-induced nausea. Secondary objectives included assessment of the effectiveness and cost-effectiveness of the wristbands in relation to vomiting and quality of life and exploration of any age, gender and emetogenic risk effects. The trial was conducted in outpatient chemotherapy clinics in three regions in the UK involving 14 different cancer units/centres. Chemotherapy-naïve cancer patients were included receiving chemotherapy of low, moderate and high emetogenic risk. The intervention were acupressure wristbands pressing the P6 point (anterior surface of the forearm), sham-wrist bands providing no pressure on acupuncture-points or no wrist-bands at all; all three groups had standard care in addition. The main outcome measures were the Rhodes Index for Nausea/Vomiting, the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool and the Functional Assessment of Cancer Therapy – General (FACT-G). At baseline participants also completed measures of anxiety/depression, nausea/vomiting expectation and expectations from using the wristbands.

In total, 500 patients were randomised (166 standard care, 166 sham acupressure + standard care, and 168 acupressure + standard care). Data were available for 361 participants for the primary outcome. The primary outcome analysis (nausea in cycle 1) revealed no differences between the three arms. Women responded more favourably to the use of sham acupressure wristbands than men. No significant differences were detected in relation to vomiting outcomes, anxiety and quality of life. Some transient adverse effects were reported, including tightness in the area of the wristbands, feeling uncomfortable when wearing them and minor swelling in the wristband area.There were no statistically significant cost differences associated with the use of real acupressure bands.

In total, 26 patients took part in qualitative interviews. The qualitative data suggested that participants perceived the wristbands (both real and sham) as effective and helpful in managing their nausea during chemotherapy.

The authors concluded that there were no statistically significant differences between the three arms in terms of nausea, vomiting and quality of life.

Intriguingly, this study was published in two different journals; and the second article reporting the identical data concluded that no clear recommendations can be made about the use of acupressure wristbands in the management of chemotherapy-related nausea and vomiting.

A further equally new study tested acupressure for post-operative nausea/vomiting. One hundred and thirty-four healthy, non-smoking women scheduled for breast surgery were randomised either to P6 stimulation or to sham control. Wristbands were applied and covered with a dressing before induction of anaesthesia. Follow-up was carried out three times within 24 h postoperative. Primary outcomes were postoperative nausea and/or vomiting.

One hundred and twelve patients completed the study. There were no statistically significant differences in the incidence of nausea or vomiting. Approximately, one third of the patients reported adverse-effects caused by the wristband, for example, redness, swelling and tenderness.

The authors of this trial concluded as follows: We did not find the Vital-Band effective in preventing either nausea or vomiting after operation in women undergoing breast surgery.

There has been quite a bit of previous research on acupressure. The most recent summary included 2 meta-analyses, 6 systematic reviews and 39 RCTs of acupressure for various conditions. Its authors stated that the strongest evidence was for pain (particularly dysmenorrhoea, lower back and labour), post-operative nausea and vomiting.

So, is acupressure effective in reducing nausea and vomiting or not? The evidence is contradictory to a degree that is baffling. If we look closer at the existing trials, we are likely to find that the more rigorous studies and those published by researchers who do not have an axe to grind tend to produce negative findings. I am therefore not convinced that acupressure has any effects beyond placebo.

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