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

systematic review

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Lots of people have commented on King Charles’ swollen hands which can be seen in many pictures, not least the one on the cover of my biography of Charles. The king himself repeatedly referred to his ‘sausage fingers’ and has made light of the issue as far back as 1982. When William was born. At that time, he wrote to a friend: “I can’t tell you how excited and proud I am. He really does look surprisingly appetising and has sausage fingers just like mine.”

Now that he is King, we might need to worry; are his ‘sausage fingers’ a sign of a serious underlying disease?

Swollen fingers are normally due to fluid retention which can have many causes, e.g.:

Charles, The Alternative Prince: An Unauthorised Biography

  • allergy,
  • arthritis,
  • bursitis,
  • carpal tunnel syndrome,
  • diabetes,
  • gout,
  • heart failure,
  • injury,
  • infection,
  • kidney failure,
  • lymphoedema,
  • scleroderma,
  • sickle cell disease,
  • syphilis,
  • tendinitis,
  • tuberculosis.

The list is long and it contains some worrying diseases. Luckily, we can exclude many of them simply because Charles has had ‘sausage fingers’ for so many years. Thus, plausible options could be diabetes and scleroderma. The former can probably be excluded mainly because we would have long known about it.

But what about scleroderma?

Scleroderma (or systemic sclerosis, as it is also called) is a serious autoimmune condition that may be localized or generalized. The latter form is more serious. In 2020, it was noted that Charles’s feet also seemed to be swollen. In addition, his face often looks flushed (see also the cover of my book).

I know far too little about Charles’s health to make even a tentative diagnosis. Some features of scleroderma fit quite well, while others do not. In any case, I do hope Charles’s swellings have a more benign explanation. But, if scleroderma is the cause, the question obviously arises: is there a so-called alternative medicine (SCAM) for it?

A recent review stated that some study results have shown that vitamins D and E, probiotics, turmeric, l-arginine, essential fatty acids, broccoli, biofeedback, and acupuncture may be beneficial in systemic sclerosis care. However, large randomized clinical trials have not been conducted. In other words, SCAM has no proven benefit for the condition, and I would not recommend it.

Charles does know that, of course. In the past, he regularly made grand proclamations in favor of SCAM but, as soon as he was really ill, he always employed the best conventional healthcare can offer.

Traditional, complementary, and alternative medicine (TCAM) – as most of my readers know, I prefer the abbreviation SCAM for so-called alternative medicine – refers to a broad range of health practices and products typically not part of the ‘conventional medicine’ system. Its use is substantial among the general population. TCAM products and therapies may be used in addition to, or instead of, conventional medicine approaches, and some have been associated with adverse reactions or other harms.

The aims of this systematic review were to identify and examine recently published national studies globally on the prevalence of TCAM use in the general population, to review the research methods used in these studies, and to propose best practices for future studies exploring the prevalence of use of TCAM.

MEDLINE, Embase, CINAHL, PsycINFO, and AMED were searched to identify relevant studies published since 2010. Reports describing the prevalence of TCAM use in a national study among the general population were included. The quality of included studies was assessed using a risk of bias tool developed by Hoy et al. Relevant data were extracted and summarised.

Forty studies from 14 countries, comprising 21 national surveys and one cross-national survey, were included. Studies explored the use of TCAM products (e.g. herbal medicines), TCAM practitioners/therapies, or both. Included studies used different TCAM definitions, prevalence time frames and data collection tools, methods and analyses, thereby limiting comparability across studies. The reported prevalence of use of TCAM (products and/or practitioners/therapies) over the previous 12 months was 24–71.3%.

The authors concluded that the reported prevalence of use of TCAM (products and/or practitioners/therapies) is high, but may underestimate use. Published prevalence data varied considerably, at least in part because studies utilise different data collection tools, methods and operational definitions, limiting cross-study comparisons and study reproducibility. For best practice, comprehensive, detailed data on TCAM exposures are needed, and studies should report an operational definition (including the context of TCAM use, products/practices/therapies included and excluded), publish survey questions and describe the data-coding criteria and analysis approach used.

[Trends in prevalence of TCAM use by country for countries with at least two data collection waves from a nationally representative study. For data collected over several years (e.g. 2007–2009), the prevalence data are plotted at the end of the data collection period (e.g. 2009). Solid and perforated lines between consecutive points are for illustrative purposes only and are not intended to represent linearity. NHANES National Health and Nutrition Examination Survey, NHIS National Health and Interview Survey, SLAN Survey of Lifestyle, Attitudes and Nutrition.]

The review discloses that the prevalence reported across countries ranges from 24 to 71%. This huge variability is not very surprising; some of the many reasons for this phenomenon include:

  • different TCAM definitions,
  • different prevalence time frames,
  • different data collection tools,
  • different methods of analyzing the data.

Despite these problems, the information summarized in the review is fascinating in several respects. For me, the most interesting message here is this: the plethora of claims that SCAM use is increasing are not supported by sound evidence.

An article in THE TIMES seems worth mentioning. Here are some excerpts:

… Maternity care at Nottingham University Hospitals NHS Trust (NUH) is the subject of an inquiry, prompted by dozens of baby deaths. More than 450 families have now come forward to take part in the review, led by the expert midwife Donna Ockenden. The trust now faces further scrutiny over its use of aromatherapy, after experts branded guidelines at the trust “shocking” and not backed by evidence. Several bereaved families have said they recall aromatherapy being heavily promoted at the trust’s maternity units.

It is being prosecuted over the death of baby Wynter Andrews just 23 minutes after she was born in September 2019. Her mother Sarah Andrews wrote on Twitter that she remembered aromatherapy being seen as “the answer to everything”. Internal guidelines, first highlighted by the maternity commentator Catherine Roy, suggest using essential oils if the placenta does not follow the baby out of the womb quickly enough…  the NUH guidelines say aromatherapy can help expel the placenta, and suggest midwives ask women to inhale oils such as clary sage, jasmine, lavender or basil, while applying others as an abdominal compress. They also describe the oils as “extremely effective for the prevention of and, in some cases, the treatment of infection”. The guidelines also suggest essential oils to help women suffering from cystitis, or as a compress on a caesarean section wound. Nice guidelines for those situations do not recommend aromatherapy…

The NUH adds frankincense “may calm hysteria” and is “recommended in situations of maternal panic”. Roy said: “It is shocking that dangerous advice seemed to have been approved by a team of healthcare professionals at NUH. There is a high tolerance for pseudoscience in NHS maternity care … and it needs to stop. Women deserve high quality care, not dangerous quackery.” …

________________________________

The journalist who wrote the article also asked me for a comment, and I emailed her this quote: “Aromatherapy is little more than a bit of pampering; no doubt it is enjoyable but it is not an effective therapy for anything. To use it in medical emergencies seems irresponsible to say the least.” The Times evidently decided not to include my thoughts.

Having now read the article, I checked again and failed to find good evidence for aromatherapy for any of the mentioned conditions. However, I did find an article and an announcement both of which are quite worrying, in my view:

Aromatherapy is often misunderstood and consequently somewhat marginalized. Because of a basic misinterpretation, the integration of aromatherapy into UK hospitals is not moving forward as quickly as it might. Aromatherapy in UK is primarily aimed at enhancing patient care or improving patient satisfaction, and it is frequently mixed with massage. Little focus is given to the real clinical potential, except for a few pockets such as the Micap/South Manchester University initiative which led to a Phase 1 clinical trial into the effects of aromatherapy on infection carried out in the Burns Unit of Wythenshawe Hospital. This article discusses the expansion of aromatherapy within the US and follows 10 years of developing protocols and policies that led to pilot studies on radiation burns, chemo-induced nausea, slow-healing wounds, Alzheimers and end-of-life agitation. The article poses two questions: should nursing take aromatherapy more seriously and do nurses really need 60 hours of massage to use aromatherapy as part of nursing practice?

My own views on aromatherapy are expressed in our now not entirely up-to-date review:

Aromatherapy is the therapeutic use of essential oil from herbs, flowers, and other plants. The aim of this overview was to provide an overview of systematic reviews evaluating the effectiveness of aromatherapy. We searched 12 electronic databases and our departmental files without restrictions of time or language. The methodological quality of all systematic reviews was evaluated independently by two authors. Of 201 potentially relevant publications, 10 met our inclusion criteria. Most of the systematic reviews were of poor methodological quality. The clinical subject areas were hypertension, depression, anxiety, pain relief, and dementia. For none of the conditions was the evidence convincing. Several SRs of aromatherapy have recently been published. Due to a number of caveats, the evidence is not sufficiently convincing that aromatherapy is an effective therapy for any condition.

In this context, it might also be worth mentioning that we warned about the frequent usage of quackery in midwifery years ago. Here is our systematic review of 2012 published in a leading midwifery journal:

Background: in recent years, several surveys have suggested that many midwives use some form of complementary/alternative therapy (CAT), often without the knowledge of obstetricians.

Objective: to systematically review all surveys of CAT use by midwives.

Search strategy: six electronic databases were searched using text terms and MeSH for CAT and midwifery.

Selection criteria: surveys were included if they reported quantitative data on the prevalence of CAT use by midwives.

Data collection and analysis: full-text articles of all relevant surveys were obtained. Data were extracted according to pre-defined criteria.

Main results: 19 surveys met the inclusion criteria. Most were recent and from the USA. Prevalence data varied but were usually high, often close to 100%. Much use of CATs does not seem to be supported by strong evidence for efficacy.

Conclusion: most midwives seem to use CATs. As not all CATs are without risks, the issue should be debated openly.

I am tired of saying ‘I TOLD YOU SO!’ but nevertheless find it a pity that our warning remained (yet again) unheeded!

Despite considerable doubts about its effectiveness, osteopathic manipulative treatment (OMT) continues to be used for a range of pediatric conditions. Here is just one example of many osteopaths advertising their services:

I qualified as an Osteopath in 2009 after 4 years of intensive training from the British College of Osteopathic medicine, where I received a distinction for my efforts. After having two children I decided to do a 2-year Postgraduate training in Pediatric Osteopathy from the Osteopathic Centre for Children in London. Whilst at the centre I was lucky enough to meet a wide variety of children from premature babies in a Neonate Hospital ward to children with developmental issues and disabilities, children on the Autistic spectrum, to kids doing exams or experiencing high levels of stress. We also saw lots of children with normal coughs, colds, lumps and bumps.

And the ‘Institute of Osteopathy states this:

Parents visit osteopaths for a range of reasons to support their child’s health. Children, like adults, can be affected by general joint and muscle issues, which is one of the reasons people visit an osteopath. Parents will also take their children to visit an osteopath for a variety of other health reasons that may benefit from osteopathic care.

As osteopathic care is based on the individual needs of the patient, it will vary depending on your child’s age and the diagnosis. Osteopaths generally use a wide range of gentle hands-on techniques that focus on releasing tension, improving mobility and optimising function. This is often used together with exercise and helpful advice. Some osteopaths have been trained in very gentle techniques which are particularly suitable to assess and treat very young children, including new-borns. You do not need to consult your GP before you visit an osteopath, although you may wish to do so.

So, how good or bad is osteopathy for kids? Our systematic review wanted to find out. Specifically, the aim of this paper is to update our previous systematic review (SR) initially published in 2013 by critically evaluating the evidence for or against this treatment.

Eleven databases were searched (January 2012 to November 2021). Only randomized clinical trials (RCTs) of OMT in pediatric patients compared with any type of controls were considered. The Cochrane risk-of-bias tool was used. In addition, the quality of the evidence was rated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, as recommended by the Cochrane Collaboration.

Thirteen trials met the eligibility criteria, of which four could be subjected to a meta-analysis. The findings show that, in preterm infants, OMT has little or no effect on reducing the length of hospital stay (standardized mean difference (SMD) -0.03; 95% confidence interval (CI) -0.44 to 0.39; very low certainty of the evidence) when compared with usual care alone. Only one study (8.3%) was judged to have a low risk of bias and showed no effects of OMT on improving exclusive breastfeeding at one month. The methodological quality of RCTs published since 2013 has improved. However, adverse effects remain poorly reported.

We concluded that the quality of the primary trials of OMT has improved during recent years. However, the quality of the totality of the evidence remains low or very low. Therefore, the effectiveness of OMT for selected pediatric populations remains unproven.

These days, it is not often that I am the co-author of a systematic review. So, allow me to discuss one of my own papers for a change by making a few very brief points:

  • Considering how many osteopaths treat children, the fact that only 13 trials exist is shameful. To me, it suggests that the osteopathic profession has little interest in research.
  • The finding that adverse effects are poorly reported is even more shameful, in my view. It suggests that the few osteopaths who do some research don’t mind violating research ethics.
  • The fact that overall our review fails to yield good evidence that osteopathy is effective for any pediatric condition is the most shameful finding of them all. It means that osteopaths are either not informed about the evidence for their own approach, or that they are informed but don’t give a hoot and treat kids regardless. In both cases, they behave unethically.

Cannabis use is a frequently-discussed subject, not just in the realm of so-called alternative medicine (SCAM). In general, SCAM advocates view it as an herbal medicine and recommend it for all sorts of conditions. They also often downplay the risks associated with cannabis use. Yet, these risks might be substantial.

Cannabis potency, defined as the concentration of Δ9-tetrahydrocannabinol (THC), has increased internationally, which could increase the risk of adverse health outcomes for cannabis users. The first systematic review of the association of cannabis potency with mental health and addiction was recently published in ‘The Lancet Psychiatry’.

The authors searched Embase, PsycINFO, and MEDLINE (from database inception to Jan 14, 2021). Included studies were observational studies of human participants comparing the association of high-potency cannabis (products with a higher concentration of THC) and low-potency cannabis (products with a lower concentration of THC), as defined by the studies included, with depression, anxiety, psychosis, or cannabis use disorder (CUD).

Of 4171 articles screened, 20 met the eligibility criteria:

  • eight studies focused on psychosis,
  • eight on anxiety,
  • seven on depression,
  • and six on CUD.

Overall, higher potency cannabis, relative to lower potency cannabis, was associated with an increased risk of psychosis and CUD. Evidence varied for depression and anxiety. The association of cannabis potency with CUD and psychosis highlights its relevance in healthcare settings, and for public health guidelines and policies on cannabis sales.

The authors concluded that standardisation of exposure measures and longitudinal designs are needed to strengthen the evidence of this association.

The fact that cannabis use increases the risk of psychosis has long been general knowledge. The notion that the risk increases with increased potency of cannabis seems entirely logical and is further supported by this systematic review. Perhaps it is time to educate the public and make cannabis users more aware of these risks, and perhaps it is time that SCAM proponents negate the harm cannabis can do.

Placebo effects are a fascinating subject. In so-called alternative medicine (SCAM), they are particularly important because much of SCAM seems to rely on little more than placebo effects. Therefore, I think this new paper is of some relevance to us.

The aim of this systematic review was to quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated.

The authors concluded that the placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

The authors furthermore confirmed that “the main finding of this meta-analysis is that placebo is an important component of the effect of injective treatments for patients with KOA, with saline injections being able to provide relevant and long-lasting results not only in terms of pain relief but also with respect to stiffness resolution and function improvement. These results are both statistically and clinically significant and can be perceived by patients up to 6 months.”

I would dispute that!

To explain why it might help to read our 1995 BMJ paper on the subject:

We often and wrongly equate the response seen in the placebo arm of a clinical trial with the placebo effect. In order to obtain the true placebo effect, other non-specific effects can be identified by including an untreated control group in clinical trials. A review of the literature shows that most authors confuse the perceived placebo effect with the true placebo effect. The true placebo effect is highly variable, depending on several factors that are not fully understood. A distinction between the perceived and the true placebo effects would be helpful in understanding the complex phenomena involved in a placebo response.

In other words, what the authors picked up in their analysis (i.e. the changes that occurred in the placebo groups between the start of a trial and after placebo application) is not just the placebo response; it is, in fact, a combination of a placebo effect, concomitant interventions/care, regression towards the mean, natural history of the condition and possibly other factors.

Does it matter?

Yes, it does!

Placebo effects are not nearly as powerful and long-lasting as the authors conclude. And this means virtually all their implications for clinical practice are incorrect.

Zinc has been in the limelight recently. The reason is that it has been recommended as a preventative and/or treatment of COVID infections. The basis for such recommendations has been some trial evidence suggesting it is effective for viral respiratory tract infections (RTIs). But the evidence has been full of contradictions which means, we need a systematic review that critically evaluated the totality of the available data.

This systematic review was aimed at evaluating the benefits and risks of zinc formulations compared with controls for the prevention or treatment of acute RTIs in adults.

Seventeen English and Chinese databases were searched in April/May 2020 for randomized clinical trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality).

The authors concluded that in adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted.

The authors provide a short comment on the assumed mode of action of zinc. The rationale for topical intranasal and sublingual zinc is based on the in vitro effects of zinc ions that can inhibit viral replication, stabilize cell membranes and reduce mucosal inflammation. Other conceivable mechanisms include the activation of T lymphocytes, monocytes, and granulocytes.

The authors also remind us to be cautious: clinicians and consumers need to be aware that considerable uncertainty remains regarding the clinical efficacy of different zinc formulations, doses, and administration routes, and the extent to which efficacy might be influenced by the ever changing epidemiology of the viruses that cause RTIs. The largest body of evidence comes from sublingual lozenges and zinc gluconate and acetate salts, suggesting these are suitable choices. Yet, this does not mean that other administration routes and zinc salts are less effective. The new evidence on the prophylactic effects of low-dose nasal sprays adds weight to the otherwise inconclusive findings from the handful of RCTs evaluating zinc nasal sprays or gels for acute treatment. A minimum therapeutic dose for zinc is also yet to be determined. An earlier review suggested the minimum dose for sublingual lozenges is 75 mg. However, the present analysis does not support this conclusion. Furthermore, a daily oral dose of 15 mg has been shown to upregulate lymphocytes within days, so it is plausible that much lower doses might also be effective.

It has been reported that a recent inspection from the Care Quality Commission (CQC) found that the diagnostic imaging service at AECC University College in Parkwood Road, Bournemouth, requires improvement in three out of four areas – including patient safety. This is surprising not least because the AECC prides itself on being “a leading higher education institution in healthcare disciplines, nationally and internationally recognised for quality and excellence.”

The unannounced inspection in May this year resulted in several demands for the service to improve upon. For example, the CQC report said staff “did not receive all of the training they needed to keep patients safe” and that patient chaperones “did not receive chaperone training”. Moreover, managers were reported as not always ensuring staff were competent to operate certain equipment. In fact, there was no record of staff competencies which meant inspectors “could not tell if staff had been trained to use equipment”. General cleanliness was also found lacking in relation to certain procedures, namely no sink in any of the site’s nine ultrasound rooms (including those for transvaginal scans) – meaning staff carrying out ultrasound scanning did not have access to a clinical handwashing facility.

The CQC states on its website that it “is the independent regulator of health and adult social care in England. We make sure health and social care services provide people with safe, effective, compassionate, high-quality care and we encourage care services to improve. We monitor, inspect and regulate services. Then we publish what we find, including performance ratings, to help people choose care. Where we find poor care, we will use our powers to take action.”

No doubt, these are laudable aims. What I find, however, disappointing is that the CQC’s inspection of the AECC did not question the nature of some of the courses taught by the AECC. Earlier this year, I reported in a blog post that the AECC has announced a new MSc ‘Musculoskeletal Paediatric Health‘. This motivated me to look into the evidence for such a course. This is what I found with several Medline searches (date of the review on chiropractic for any pediatric conditions, followed by its conclusion + link [so that the reader can look up the evidence]):

2008

I am unable to find convincing evidence for any of the above-named conditions. 

2009

Previous research has shown that professional chiropractic organisations ‘make claims for the clinical art of chiropractic that are not currently available scientific evidence…’. The claim to effectively treat otitis seems to
be one of them. It is time now, I think, that chiropractors either produce the evidence or abandon the claim.

2009

The … evidence is neither complete nor, in my view, “substantial.”

2010

Although the major reason for pediatric patients to attend a chiropractor is spinal pain, no adequate studies have been performed in this area. It is time for the chiropractic profession to take responsibility and systematically investigate the efficiency of joint manipulation of problems relating to the developing musculoskeletal system.

2018

Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe.

What seems to emerge is rather disappointing:

  1. There are no really new reviews.
  2. Most of the existing reviews are not on musculoskeletal conditions.
  3. All of the reviews cast considerable doubt on the notion that chiropractors should go anywhere near children.

But perhaps I was too ambitious. Perhaps there are some new rigorous clinical trials of chiropractic for musculoskeletal conditions. A few further searches found this (again year and conclusion):

2019

We found that children with long duration of spinal pain or co-occurring musculoskeletal pain prior to inclusion as well as low quality of life at baseline tended to benefit from manipulative therapy over non-manipulative therapy, whereas the opposite was seen for children reporting high intensity of pain. However, most results were statistically insignificant.

2018

Adding manipulative therapy to other conservative care in school children with spinal pain did not result in fewer recurrent episodes. The choice of treatment-if any-for spinal pain in children therefore relies on personal preferences, and could include conservative care with and without manipulative therapy. Participants in this trial may differ from a normal care-seeking population.

I might have missed one or two trials because I only conducted rather ‘rough and ready’ searches, but even if I did: would this amount to convincing evidence? Would it be good science?

No! and No!

So, why does the AECC offer a Master of Science in ‘Musculoskeletal Paediatric Health’?

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Isn’t that a question the CQC should have asked?

Should Acupuncture-Related Therapies be Considered in Prediabetes Control?

No!

If you are pre-diabetic, consult a doctor and follow his/her advice. Do NOT do what acupuncturists or other self-appointed experts tell you. Do NOT become a victim of quackery.

But the authors of a new paper disagree with my view.

So, let’s have a look at the evidence.

Their systematic review was aimed at evaluating the effects and safety of acupuncture-related therapy (AT) interventions on glycemic control for prediabetes. The Chinese researchers searched 14 databases and 5 clinical registry platforms from inception to December 2020. Randomized controlled trials involving AT interventions for managing prediabetes were included.

Of the 855 identified trials, 34 articles were included for qualitative synthesis, 31 of which were included in the final meta-analysis. Compared with usual care, sham intervention, or conventional medicine, AT treatments yielded greater reductions in the primary outcomes, including fasting plasma glucose (FPG) (standard mean difference [SMD] = -0.83; 95% confidence interval [CI], -1.06, -0.61; P < .00001), 2-hour plasma glucose (2hPG) (SMD = -0.88; 95% CI, -1.20, -0.57; P < .00001), and glycated hemoglobin (HbA1c) levels (SMD = -0.91; 95% CI, -1.31, -0.51; P < .00001), as well as a greater decline in the secondary outcome, which is the incidence of prediabetes (RR = 1.43; 95% CI, 1.26, 1.63; P < .00001).

The authors concluded that AT is a potential strategy that can contribute to better glycemic control in the management of prediabetes. Because of the substantial clinical heterogeneity, the effect estimates should be interpreted with caution. More research is required for different ethnic groups and long-term effectiveness.

But this is clearly a positive result!

Why do I not believe it?

There are several reasons:

  • There is no conceivable mechanism by which AT prevents diabetes.
  • The findings heavily rely on Chinese RCTs which are known to be of poor quality and often even fabricated. To trust such research would be a dangerous mistake.
  • Many of the primary studies were designed such that they failed to control for non-specific effects of AT. This means that a causal link between AT and the outcome is doubtful.
  • The review was published in a 3rd class journal of no impact. Its peer-review system evidently failed.

So, let’s just forget about this rubbish paper?

If only it were so easy!

Journalists always have a keen interest in exotic treatments that contradict established wisdom. Predictably, they have been reporting about the new review thus confusing or misleading the public. One journalist, for instance, stated:

Acupuncture has been used for thousands of years to treat a variety of illnesses — and now it could also help fight one of the 21st century’s biggest health challenges.

New research from Edith Cowan University has found acupuncture therapy may be a useful tool in avoiding type 2 diabetes.

The team of scientists investigated dozens of studies covering the effects of acupuncture on more than 3600 people with prediabetes. This is a condition marked by higher-than-normal blood glucose levels without being high enough to be diagnosed as diabetes.

According to the findings, acupuncture therapy significantly improved key markers, such as fasting plasma glucose, two-hour plasma glucose, and glycated hemoglobin. Additionally, acupuncture therapy resulted in a greater decline in the incidence of prediabetes.

The review can thus serve as a prime example for demonstrating how irresponsible research has the power to mislead millions. This is why I have often said that poor research is a danger to public health.

And what can be done about this more and more prevalent problem?

The answer is easy: people need to behave more responsibly; this includes:

  • trialists,
  • review authors,
  • editors,
  • peer-reviewers,
  • journalists.

Yes, the answer is easy in theory – but the practice is far from it!

I have often called out unreliable or fraudulent research in the realm of Traditional Chinese Medicine (TCM). I think it is important to do so because the abundance of scientific misconduct is such that it has become a danger to public health. Today, I present yet another example:

This recent review claimed to summarize the evidence on TCM in treating MI, the clinical evaluations of TCM in treating male infertility (MI), and the molecular mechanisms of TCM effects. I was alerted to the fact that the authors cite a paper on acupuncture that I had co-authored. Here is the section in question from the review:

Acupuncture is one of the therapeutic techniques that are part of TCM. Acupuncture is a non-invasive technique and is regarded as free of risk if performed by trained personnel [35]. One of the advantages of acupuncture was that the incidence of adverse effects was substantially lower than that of many drugs or other accepted [35]. Acupuncture has been used in the treatment of male and female infertility and in assisted reproductive technology treatments for many years. A total of 100 patients with MI who met the diagnostic criteria were randomly divided into two groups [7]. Half of the patients received acupuncture treatment, and the other half received placebo acupuncture. After 10 weeks treatment, acupuncture successfully improved the indicators of the semen, including the spermatozoa survival rate, b-level activity rate, sperm density, sperm activity rate. A total of 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of acupuncture and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A-C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture [36]. Of the 279 cases of male sterility treated by the combination of acupuncture, pilose antler essence injection to acupoints and oral administration of Chinese materia medica, 142 cases (47.8%) were cured, 81 cases (27.3%) markedly effective, 53 cases (17.8%) effective and 21 cases (7.1%) ineffective [37]. The therapeutic effect of the combination of these three treatments was satisfactory.

Ref 7

Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

This paper does not relate to the statement it is meant to support by the review authors.

Ref 35

The review by Qin et al (1) includes 5 trials none of which should have been included in a quality metaanalysis as the methodology was unconvincing: In the trial by Alraek et al., patients were randomised to receive either acupuncture or no treatment. This means that no attempt was made to control for the effects of placebo or extra attention. Therefore, this study does not demonstrate an effect of acupuncture as the outcome could be due to non-specific effects unrelated with this therapy. By contrast, the trial by Aune et al. did attempt to control for placebo effects by using a sham control group. Sham acupuncture was given using six needles superficially inserted in the calves, thighs or abdomen outside known acupuncture points or meridians. Needles were not manipulated in the sham group. Sham or placebo controls have the purpose of rendering patients unaware of whether they receive the real or the sham treatment. The method used here cannot achieve this aim; patients would be easily able to tell which intervention they received. In other words, this study also did not adequately control for placebo effects. The remaining three trials are all not Medline-listed, authored by Chinese investigators and published in inaccessible journals. This should disqualify them from inclusion as they were unverifiable by the peer review process. According to the published table, they were equivalence trials of acupuncture versus antibiotics with a sample size around 30. This means they are grossly underpowered and thus unable to generate reliable results. Unless BJOG peer reviewers could see the primary articles, or be provided with translations from Chinese, the systematic review should not have been accepted. The “many eyes of science” requires transparency, testing, challenge and verification. Although in the past, inconclusive results of acupuncture have not been thought to be due to Chinese influence (2), it has been noted that virtually all recent published acupuncture trials are “positive” (3), raising questions of publication and other biases. Our colleagues are under tremendous pressure to publish, but we do them no favours by effectively lowering the standard of scientific peer review. Elite journals too have an obligation to train and reiterate about publication ethics and sound scientific writing (4). As none of the primary studies convincingly demonstrated that acupuncture is an effective therapy for recurrent urinary tract infections, no positive conclusion was warranted. Although Qin et al. did state that the risk of bias of the included trials was generally high or unclear (1), the BJOG nevertheless allowed them to turn massive uncertainty into relatively firm, positive conclusions in the abstract (“Acupuncture appeared to be beneficial for treatment and prophylaxis of rUTIs”) and tweetable abstract (“This review found that acupuncture may improve treatment and prevent recurrence of urinary tract infection in women”), thus leading to excited media headlines that inevitably mislead the public. ‘May’ is a weasel word which should be avoided as it is unfalsifiable (for example, pigs do not fly but they ‘may’ fly in the future). The definite, straightforward conclusion must be “There is no good evidence to support the use of acupuncture for the treatment and prophylaxis of recurrent UTIs”. It is not acceptable to give international credibility to an implausible modality that no objective, independent high-quality review has found effective beyond placebo (5). The dampening accompanying mini-commentary (6) does not undo the damage.
The review should be withdrawn while the primary papers are translated for peer reviewers to examine, the above limitations discussed in the text, and the positive ‘spin’ in conclusions corrected. These improvements would consolidate the researchers’ probity and justify the accolade of BJOG publication.

Our letter to the editor does not bear any relation to the statement it is meant to support by the review authors.

Ref 36

In this first prospective, randomized, single-blind, placebo-controlled study, 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of traditional Chinese medicine (TCM) and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A–C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture.

This small study is far from convincing and does not lend itself to far-reaching conclusions

Ref 37

Of the 279 cases of male sterility treated by the combination of acupuncture, pilose antler
essence injection to acupoints and oral administration of Chinese materia medica, 142
cases (47.8%) were cured, 81 cases (27.3%) markedly effective, 53 cases (17.8%) effective
and 21 cases (7.1%) ineffective. The therapeutic effect of the combination of these three
treatments was satisfactory.

This study had no control group and used two different therapies. Therefore, it does not allow any conclusion about the effectiveness of acupuncture.

____________________

Perhaps you feel that these errors are trivial. But I would disagree. The review authors’ praise of acupuncture for MI is misplaced and will mislead the public. There are plenty of reviews on the subject, and those that are not overtly biased arrive at conclusions like these:

So, how did this sloppy review come about?

Its authors are affiliated to the TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China, and the Tea Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China. A footnote tells us that their review was supported by the National Natural Science Foundation of China [No. 81973647] and the Xinglin scholar discipline promotion talent program of Chengdu University of traditional Chinese medicine [No. BSH2021018]. This sounds respectable enough.

The journal that published the review is ‘Pharmacological Research – Modern Chinese Medicine‘. Its stated aims are as follows: The journal publishes articles reporting on advances in our comprehension of mechanism and safety in experimental pharmacology and clinical efficacy and safety of pharmacologically active substances, including compound prescriptions, utilized in Traditional Chinese Medicine applying modern scientific research methods. Studies reporting also on the mechanisms of actions of the active substance(s) investigated are encouraged.

The editors in chief of the journal are Guan-Hua Du, PhD, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica, Beijing, China and Emilio Clementi, M.Mus, MD, PhD, University of Milan, Milan, Italy. No doubt, these are respectable scientists. And because they are, they should make sure that what they publish is correct – a criterion this recent review clearly does not meet.

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