case-control study

1 2 3 5

This analysis was aimed at assessing the associations of acupuncture use with mortality, readmission and reoperation rates in hip fracture patients using a longitudinal population-based database. A retrospective matched cohort study was conducted using data for the years 1996-2012 from Taiwan’s National Health Insurance Research Database. Hip fracture patients were divided into:

  • an acupuncture group consisting of 292 subjects who received at least 6 acupuncture treatments within 183 days of hip fracture,
  • and a propensity score matched “no acupuncture” group of 876 subjects who did not receive any acupuncture treatment and who functioned as controls.

The two groups were compared using survival analysis and competing risk analysis.

Compared to non-treated subjects, subjects treated with acupuncture had

  • a lower risk of overall death (hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.24-0.73, p = 0.002),
  • a lower risk of readmission due to medical complications (subdistribution HR (sHR): 0.64, 95% CI: 0.44-0.93, p = 0.019)
  • and a lower risk of reoperation due to surgical complications (sHR: 0.62, 95% CI: 0.40-0.96, p = 0.034).

The authors concluded that postoperative acupuncture in hip fracture patients is associated with significantly lower mortality, readmission and reoperation rates compared with those of matched controls.

That’s a clear and neat finding; the question is, what does it mean?

Here are a few possibilities for consideration:

  1. As a result of having at least 6 acupuncture sessions, patients had lower rates of mortality, readmission and reoperation.
  2. As a result of having lower rates of mortality, readmission and reoperation, patients used acupuncture.
  3. As a result of some other factor, patients had both lower rates of mortality, readmission and reoperation and at least 6 sessions of acupuncture.

Which of the three possibilities is the most likely?

  1. Some enthusiasts might think that acupuncture makes you live longer. But does anyone truly believe it reduces the likelihood of needing a reoperation? Seriously? Well, I don’t see even a hint of a mechanism by which acupuncture might achieve this. Therefore, I would categorise this possibility as highly unlikely.
  2. It stands to reason that patients who are alive and well use more acupuncture than those who are dead or in need of surgery. So, this possibility is not entirely inconceivable.
  3. It seems very likely that people who are more health conscious might use acupuncture and live longer, need less readmissions or surgery. No doubt, this possibility is by far the best explanation of the findings of this retrospective matched cohort study.

If that is so, does this paper tell us anything useful at all?

Not really (that’s why it was published in an acupuncture journal which few people would read)

On second thought, perhaps it does tell us something valuable: retrospective matched cohort studies are hopeless when it comes to establishing cause and effect!

Glucosamine is currently one of the most popular of all dietary supplements. It is marketed as a treatment for arthritis, and there is some evidence that it is moderately helpful for this indication. But evidence had been accumulating to suggest that glucosamine might have other effects as well. The latest analysis evaluated the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.

This population-based prospective cohort study included 495 077 women and men from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. The investigators evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.

At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).

The authors concluded that regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Previous epidemiological investigations indicated that glucosamine use might play a role in prevention of cancer, cardiovascular disease and other diseases. This suggests that the finding is more than the result of a large ‘fishing expedition’ to which epidemiological studies are sadly prone. It we are indeed dealing with a true phenomenon, we should ask by what mechanism these remarkable outcomes might be achieved. It is well documented that glucosamine has powerful anti-inflammatory effects. Therefore it is conceivable that such anti-inflammatory mechanisms are the cause for the observed outcomes.

How do we prove or disprove the hypothesis that glucosamine reduces the mortality of a range of diseases? A reasonable starting point would be to consult the good old Hill criteria of causality:

(1) The strength of association is small to moderate – certainly not strong

(2) The consistency of the findings is quite remarkable; that is unless dozens of epidemiological studies that failed to yield and association were never published.

(3) The specificity of the association with diseases linked to inflammation is also impressive (with the caveat above).

(4) Temporality seems also not a problem, as far as I can see.

(5) Biological gradient needs further testing, I think.

(6) Plausibility is not a problem, since there is a possible mechanism that could explain the findings.

(7) The same applies to coherence.

(8) Experiment is needed, but it is far from easy to conduct clinical trials where mortality is an endpoint.

(9) Analogy is realised through the well-established concept of (cardiovascular) risk factors.

What does all this actually mean?

It means, I think, that glucosamine could well have clinical effects that go far beyond easing the pain of arthritis. However, we cannot be sure. Once again, it boils down to the need of robust clinical trial data. The subject certainly seems important enough to consider this option.


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

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

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

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

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

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

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

In their paper, the authors state this:

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

My comments to this are as follows:

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

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

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

When I first saw this press-release, I thought it was a hoax. After all, it came from a most dubious homeopathic source. Then I read it again and was no longer sure.

What do you think?

Here it is in full:

Santa Clara, Cuba, April 3,2020 (Prensa Latina) The homeopathic medicine Prevengho-VIR began to be administered as a measure to confront the Covid-19 in this province of central Cuba.

Dr. Mirtha Rosa Hernandez, head of the Department of the Elderly in Villa Clara, reported that the supply of the preparation began in the Grandparents’ Homes and Elderly Homes of the territory, which has 184,000 people over 60 years old, 23.9 percent of the local universe. The medicine is administered by doctors and nurses of the basic working group where the Grandparents’ Homes and Nursing Homes are located in the 13 municipalities of this province.

This homeopathic medicine comes in a 10-milliliter bottle, and the daily dosage is 5 drops, thrice a day; while on the tenth day a reactivation of the initial dose is performed. It is aimed at preventing the respiratory diseases in this risk group, in addition to other medical conditions, such as dengue.

In the upcoming days it will be extended to the Maternal Homes. It is administered by the doctors and the nurses from the basic work group of the senior homes.

She said, that besides avoiding the new coronavirus the formula is also aimed at preventing respiratory diseases in this risk group, in addition to others such as dengue fever.

This medicine can also be administered to children under 10 years old, pregnant women, nursing mothers, and patients with liver disorders.

Combination Medicine
Anas berberiae 200
Baptisia tinctora 200
Bascilinum 30
Pyrogenum 200
Eupetorium perf 200
Influezinum 200
Arsenicum Album 200

As I said, I was not sure whether this was for real. Is it possible that even officials are so stupid, brainwashed or gullible to go for homeopathy in such a serious situation?

In an attempt to find out, I did a little search and quickly found that the story has been reported by multiple media. This, for instance, is what the Miami Herald reported:

As scientists around the world speed up clinical trials to find a cure or vaccine for the coronavirus, the Cuban government will begin distributing a homeopathic remedy to the elderly and other vulnerable people to “prevent” the spread of the disease, a top health official said.

Dr. Francisco Durán, national director of Epidemiology at the Ministry of Public Health, said in a press conference on Sunday that “sublingual drops” of the compound PrevengHo-Vir “prevent different diseases such as influenza, the common cold, dengue, and emerging viral infections such as this one.”

On Monday, Durán tried to correct his statements and said that the product “does not prevent contagion” but rather “increases resistance, the body’s defenses against a certain virus.”

Several state media outlets reported that PrevengHo-Vir is already being used in various Cuban provinces to treat the elderly and other groups vulnerable to the coronavirus. There is no internet record of PrevengHo-Vir, other than press reports about the announcement of its distribution in Cuba.

So, it’s not a hoax!

In this case, let me try to predict what will happen next:

  • When the pandemic is over, the Cubans will publish mortality rates achieved with their homeopathic prevention [A].
  • They will compare them to data from a cohort that did not receive the homeopathic treatment [B].
  • Neither of the data-sets will be transparent and nobody will be able to check its reliability.
  • The comparison will yield a significant difference in favour of homeopathy.
  • The Cubans will use this to market their remedy.
  • The world of homeopathy will use it as a proof that homeopathy is effective (it wouldn’t be the first time).

Nothing wrong with that, some will say. Others who understand research methodology will, however, point out that these data are less than convincing.

In such case/control studies, one large group of patients [A] is compared to another group [B]. Group A has been treated homeopathically, while group B received no homeopathy. Any difference in outcome between A and B might be due to a range of circumstances that are unrelated to the homeopathic treatment, for instance:

  • group A might have been less ill than group B,
  • group A might have been better nourished,
  • group A might have benefited from better hygiene,
  • group A might have received better care,
  • group B might have received treatments that made the situation not better but worse,
  • the researchers might have prettified the data to make group A look better.

Such concerns are not totally unfounded; after all, Cuba seems to have a long history of making irresponsible claims for their homeopathic products.

During my almost 30 years of research into so-called alternative medicine (SCAM), I have published many papers which must have been severe disappointments to those who advocate SCAM or earn their living through it. Many SCAM proponents thus reacted with open hostility. Others tried to find flaws in those articles which they found most upsetting with a view of discrediting my work. The 2012 article entitled ‘A Replication of the Study ‘Adverse Effects of Spinal Manipulation: A Systematic Review‘ by the Australian chiropractor, Peter Tuchin, seems to be an example of the latter phenomenon (used recently by Jens Behnke in an attempt to defame me).

Here is the abstract of the Tuchin paper:

Objective: To assess the significance of adverse events after spinal manipulation therapy (SMT) by replicating and critically reviewing a paper commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy Soc Med 100:330-338, 2007).

Method: Replication of a 2007 Ernst paper to compare the details recorded in this paper to the original source material. Specific items that were assessed included the time lapse between treatment and the adverse event, and the recording of other significant risk factors such as diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of hypertension, atherosclerosis and migraine.

Results: The review of the 32 papers discussed by Ernst found numerous errors or inconsistencies from the original case reports and case series. These errors included alteration of the age or sex of the patient, and omission or misrepresentation of the long term response of the patient to the adverse event. Other errors included incorrectly assigning spinal manipulation therapy (SMT) as chiropractic treatment when it had been reported in the original paper as delivered by a non-chiropractic provider (e.g. Physician).The original case reports often omitted to record the time lapse between treatment and the adverse event, and other significant clinical or risk factors. The country of origin of the original paper was also overlooked, which is significant as chiropractic is not legislated in many countries. In 21 of the cases reported by Ernst to be chiropractic treatment, 11 were from countries where chiropractic is not legislated.

Conclusion: The number of errors or omissions in the 2007 Ernst paper, reduce the validity of the study and the reported conclusions. The omissions of potential risk factors and the timeline between the adverse event and SMT could be significant confounding factors. Greater care is also needed to distinguish between chiropractors and other health practitioners when reviewing the application of SMT and related adverse effects.

The author of this ‘replication study’ claims to have identified several errors in my 2007 review of adverse effects of spinal manipulation. Here is the abstract of my article:

Objective: To identify adverse effects of spinal manipulation.

Design: Systematic review of papers published since 2001.

Setting: Six electronic databases.

Main outcome measures: Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports.

Results: The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature.

Conclusions: Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation.

In my view, there are several things that are strange here:

  1. Tuchin published his paper 5 years after mine.
  2. He did not publish it in the same journal as my original, but in an obscure chiro journal that hardly any non-chiropractor would ever read.
  3. Tuchin never contacted me and never alerted me to his publication.
  4. The journal that Tuchin chose was not Medline-listed in 2012; consequently, I never got to know about the Tuchin article in a timely fashion. (Therefore, I did never respond to it.)
  5. A ‘replication study’ is a study that repeats the methodology of a previous study.
  6. Tuchin’s paper is therefore NOT a replication study. Firstly, mine was a review and not a study. Secondly, and crucially, Tuchin never repeated my methodology but used an entirely different one.

But arguably, these points are trivial. They should not distract from the fact that I might have made mistakes. So, let’s look at the substance of Tuchin’s claim, namely that I made errors or omissions in my review.

As to ‘omissions’, one could argue that a review such as mine will always have to omit some details in order to generate a concise summary. The only way to not omit any details is to re-publish all the primary papers in one large volume. Yet, this can hardly be the purpose of a systematic review.

As to the ‘errors’, it seems that the ages and sex of three patients were wrong (I have not checked this against the primary publications but, for the moment, I believe Tuchin). This is, of course, lamentable and – even though I have no idea whether the errors happened at the data extraction phase, during the typing, the revising, or the publishing of the paper – it is entirely my responsibility. I also seem to have mistaken a non-chiropractor for a chiropractor. This too is regrettable but, as the review was about spinal manipulation and not about chiropractic, the error is perhaps not so grave.

Be that as it may, these errors are unquestionably not good, and I can only apologise for them. If Tuchin had dealt with them in the usual way – by publishing in a timely fashion a ‘letter to the editor’ of the JRSM – I could have easily corrected them for everyone to see.

But I think there is a more important point to be made here:

Tuchin concludes his paper stating that it is unwise to make conclusions regarding causality from any case study or multiple case studies. The number of errors or omissions in the 2007 Ernst paper significantly limit any reported conclusions. I believe that both sentences are unjustified. The safety of any intervention in routine use has to be examined on the basis of published case studies. This is particularly true for chiropractic where no post-marketing surveillance similar to that for drugs exists.

The conclusions based on such evidence can, of course, never be firm, but they provide valuable signals that can prompt more rigorous investigations in the interest of patient safety. In view of such considerations, my own conclusions in my 2007 paper were, I think, correct and are NOT invalidated by my relatively trivial mistakes: spinal manipulation, particularly when performed on the upper spine, has repeatedly been associated with serious adverse events. Currently the incidence of such events is unknown. Adherence to informed consent, which currently seems less than rigorous, should therefore be mandatory to all therapists using this treatment. Considering that spinal manipulation is used mostly for self-limiting conditions and that its effectiveness is not well established, we should adopt a cautious attitude towards using it in routine health care. 

And my conclusions in the abstract have now, I believe, become established wisdom. They are thus even less in jeopardy through my calamitous lapsus or Tuchin’s ‘replication study’: Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. 



A team of chiropractic researchers conducted a review of the safety of spinal manipulative therapy (SMT) in children under 10 years. They aimed to:

1) describe adverse events;

2) report the incidence of adverse events;

3) determine whether SMT increases the risk of adverse events compared to other interventions.

They searched MEDLINE, CINAHL, and Index to Chiropractic Literature from January 1, 1990 to August 1, 2019. Eligible studies were case reports/series, cohort studies and randomized controlled trials. Studies of high and acceptable methodological quality were included.

Most adverse events are mild (e.g., increased crying, soreness). One case report describes a severe adverse event (rib fracture in a 21-day-old) and another an indirect harm in a 4-month-old. The incidence of mild adverse events ranges from 0.3% (95% CI: 0.06, 1.82) to 22.22% (95% CI: 6.32, 54.74). Whether SMT increases the risk of adverse events in children is unknown.

The authors concluded that the risk of moderate and severe adverse events is unknown in children treated with SMT. It is unclear whether SMT increases the risk of adverse events in children < 10 years.

Thanks to their ingenious methodology, the authors managed to miss 11 of the 13 studies included in the review by Vohra et al which reported 9 serious adverse events and 20 cases of delayed diagnosis associated with SMT. Another review reported 15 serious adverse events and 775 mild to moderate adverse events following manual therapy. As far as I can see, the authors of the new review make just one reasonable point:

We recommend the implementation of a population-based active surveillance program to measure the incidence of severe and serious adverse events following SMT treatment in this population.

In the absence of such a surveillance system, any incidence figures are not just guess-work but also a depiction of the tip of a much bigger iceberg. So, why do the authors of this review not make this point clearly and powerfully? Why does the review read mostly like an attempt to white-wash a thorny subject? Why do they not provide a breakdown of the adverse events according to profession? The answer to these questions can be found at the very end of the paper:

This study was supported by the College of Chiropractors of British Columbia to Ontario Tech University. The College of Chiropractors of British Columbia was not involved in the design, conduct or interpretation of the research that informed the research. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program to Pierre Côté who holds the Canada Research Chair in Disability Prevention and Rehabilitation at Ontario Tech University, and from the Canadian Chiropractic Research Foundation to Carol Cancelliere who holds a Research Chair in Knowledge Translation in the Faculty of Health Sciences at Ontario Tech University.

This study was supported by the College of Chiropractors of British Columbia to Ontario Tech University. The College of Chiropractors of British Columbia was not involved in the design, conduct or interpretation of the research that informed the research. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program to Pierre Côté who holds the Canada Research Chair in Disability Prevention and Rehabilitation at Ontario Tech University, and funding from the Canadian Chiropractic Research Foundation to Carol Cancelliere who holds a Research Chair in Knowledge Translation in the Faculty of Health Sciences at Ontario Tech University.

I have often felt that chiropractic is similar to a cult. An investigation by cult members into the dealings of a cult is not the most productive of concepts, I guess.

This review provides published data on so-called alternative medicine (SCAM)-related liver injuries (DILI) in Asia, with detail on incidences, lists of most frequently implicated herbal remedies, along with analysis of patient population and their clinical outcomes.

Its authors conclude that SCAM use is widely prevalent in Asia and is associated with, among other adverse effects, hepatotoxicity. Both proprietary as well as non-proprietary or traditional SCAMs have been implicated in hepatotoxicity. Acute hepatocellular pattern of liver injury is the most common type of liver injury seen, and the spectrum of liver-related adverse events range from simple elevation of liver enzymes to the very serious ALF and ACLF, which may, at times, require liver transplant.

SCAM-related liver injury is one among the major causes for hepatotoxicity, including ALF and ACLF worldwide, with high incidence among Asian countries. Patient outcomes associated with SCAM-DILI are generally poor, with very high mortality rates in those with chronic liver disease. Stringent regulations, at par with that of conventional modern medicine, are required, and may help improve safety of patients seeking SCAM for their health needs. Regional surveillance including post-marketing analysis from government agencies associated with drug regulation and control in tandem with national as well as regional level hepatology societies are important for understanding the true prevalence of DILI associated with SCAM. An integrated approach used by practitioners combining conventional and traditional medicine to identify safety and efficacy of SCAMs is an unmet need in most of the Asian countries. Endorsement of scientific methodology with good quality preclinical and clinical trials and abolishment of unhealthy publication practices is an area that needs immediate attention in SCAM practice. Such holistic standard science-based approaches could help ameliorate liver disease burden in the general and patient population.

I congratulate the authors to this excellent paper. It contains a wealth of information and is well worth reading in full. The review will serve me as a valuable source of data for many years to come.

systematic review of the evidence for effectiveness and harms of specific spinal manipulation therapy (SMT) techniques for infants, children and adolescents has been published by Dutch researchers. I find it important to stress from the outset that the authors are not affiliated with chiropractic institutions and thus free from such conflicts of interest.

They searched electronic databases up to December 2017. Controlled studies, describing primary SMT treatment in infants (<1 year) and children/adolescents (1–18 years), were included to determine effectiveness. Controlled and observational studies and case reports were included to examine harms. One author screened titles and abstracts and two authors independently screened the full text of potentially eligible studies for inclusion. Two authors assessed risk of bias of included studies and quality of the body of evidence using the GRADE methodology. Data were described according to PRISMA guidelines and CONSORT and TIDieR checklists. If appropriate, random-effects meta-analysis was performed.

Of the 1,236 identified studies, 26 studies were eligible. In all but 3 studies, the therapists were chiropractors. Infants and children/adolescents were treated for various (non-)musculoskeletal indications, hypothesized to be related to spinal joint dysfunction. Studies examining the same population, indication and treatment comparison were scarce. Due to very low quality evidence, it is uncertain whether gentle, low-velocity mobilizations reduce complaints in infants with colic or torticollis, and whether high-velocity, low-amplitude manipulations reduce complaints in children/adolescents with autism, asthma, nocturnal enuresis, headache or idiopathic scoliosis. Five case reports described severe harms after HVLA manipulations in 4 infants and one child. Mild, transient harms were reported after gentle spinal mobilizations in infants and children, and could be interpreted as side effect of treatment.

The authors concluded that, based on GRADE methodology, we found the evidence was of very low quality; this prevented us from drawing conclusions about the effectiveness of specific SMT techniques in infants, children and adolescents. Outcomes in the included studies were mostly parent or patient-reported; studies did not report on intermediate outcomes to assess the effectiveness of SMT techniques in relation to the hypothesized spinal dysfunction. Severe harms were relatively scarce, poorly described and likely to be associated with underlying missed pathology. Gentle, low-velocity spinal mobilizations seem to be a safe treatment technique in infants, children and adolescents. We encourage future research to describe effectiveness and safety of specific SMT techniques instead of SMT as a general treatment approach.

We have often noted that, in chiropractic trials, harms are often not mentioned (a fact that constitutes a violation of research ethics). This was again confirmed in the present review; only 4 of the controlled clinical trials reported such information. This means harms cannot be evaluated by reviewing such studies. One important strength of this review is that the authors realised this problem and thus included other research papers for assessing the risks of SMT. Consequently, they found considerable potential for harm and stress that under-reporting remains a serious issue.

Another problem with SMT papers is their often very poor methodological quality. The authors of the new review make this point very clearly and call for more rigorous research. On this blog, I have repeatedly shown that research by chiropractors resembles more a promotional exercise than science. If this field wants to ever go anywhere, if needs to adopt rigorous science and forget about its determination to advance the business of chiropractors.

I feel it is important to point out that all of this has been known for at least one decade (even though it has never been documented so scholarly as in this new review). In fact, when in 2008, my friend and co-author Simon Singh, published that chiropractors ‘happily promote bogus treatments’ for children, he was sued for libel. Since then, I have been legally challenged twice by chiropractors for my continued critical stance on chiropractic. So, essentially nothing has changed; I certainly do not see the will of leading chiropractic bodies to bring their house in order.

May I therefore once again suggest that chiropractors (and other spinal manipulators) across the world, instead of aggressing their critics, finally get their act together. Until we have conclusive data showing that SMT does more good than harm to kids, the right thing to do is this: BEHAVE LIKE ETHICAL HEALTHCARE PROFESSIONALS: BE HONEST ABOUT THE EVIDENCE, STOP MISLEADING PARENTS AND STOP TREATING THEIR CHILDREN!

Many cancer patients use so-called alternative medicine (SCAM) such as Traditional Chinese Medicine (TCM). On this blog, we have repeatedly discussed whether this does more good than harm. This study sheds new light on the question. Specifically, it aims to explore the benefits of TCM therapy in the long-term survival of patients with hepatocellular carcinoma in China.

In total, 3483 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled. The researchers used 1:1 frequency matching by sex, age, diagnosis time, Barcelona Clinic Liver Cancer staging, and type of treatments to compare the TCM users (n = 526) and non-TCM users (n = 526). A Cox multivariate regression model was employed to evaluate the effects of TCM therapy on the HR value and Kaplan-Meier survival curve for mortality risk in HCC patients. A log-rank test was performed to analyse the effect of TCM therapy on the survival time of HCC patients.

The Cox multivariate analysis indicated that TCM therapy was an independent protective factor for 5-year survival in patients with HCC. The Kaplan-Meier curve also showed that after PS matching, TCM users had a higher overall survival rate and a higher progression-free survival rate than non-TCM users. TCM users, regardless of the classification of etiology, tumor stage, liver function level, or type of treatment, all benefited significantly from TCM therapy. The most commonly used Chinese patent medications used were Fufang Banmao Capsule, Huaier Granule, and Jinlong Capsule.

The authors concluded that using traditional Chinese medications as adjuvant therapy can probably prolong median survival time and improve the overall survival among patients with HCC. Further scientific studies and clinical trials are needed to examine the efficiency and safety.

I was unable to access the full article and therefore am unable to provide a detailed critique of it. From reading the abstract, I should point out, however, that this was not an RCT. To minimise bias, the researchers used a matching technique to generate two comparable groups. Such methods can be successful in matching for the named parameters, but they cannot match for the plethora of variables that might be relevant but were not measured. Therefore, the survival difference between the two groups might be due not to the therapies they received, but to the fact that the groups were not comparable in terms of factors that impact on survival.

Another important point about this paper is the obvious fact that it originates from China. We know from several independent investigations that such studies almost never report negative findings. We also know that TCM is a hugely important export item for China. Adding two and two together should therefore make us sceptical. I for one take the present findings with more than a pinch of salt.

Glucosamine supplements are often advocated for the treatment of osteoarthritis. But there is evidence that they might convey other benefits as well. This prospective observational study assessed the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. The UK Biobank data of 466 039 participants without CVD at baseline was used. They completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. The main outcome measures were incident CVD events, including CVD death, coronary heart disease, and stroke.

During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00).

The authors concluded that habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.

This is an impressive study! It incorporates both a huge sample size and a long observation period. Moreover, the authors analysed the data expertly and interpreted their results with the necessary caution.

The association between glucosamine intake and CVD risk were independent of CVD risk factors, such as gender, age, income, body mass index, physical activity, healthy diet, alcohol intake, smoking status, diabetes, hypertension, high cholesterol, arthritis, drug use, and other supplement use. Moreover, the findings are in line with several previous studies that show inverse associations of glucosamine use with CVD risk and mortality. And finally, the authors discuss several biologically plausible mechanisms that could explain the observed findings.

Yet, it is conceivable that the association is not of a causal nature. There might be a host of confounders responsible for the finding. Therefore, before we now all rush to the next health-food store to buy glucosamine supplements – they are not all that cheap! – we should perhaps wait for further independent replications and research.

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