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

meta-analysis

1 2 3 8

This is an analysis that I have long hesitated to conduct. The reason for my hesitation is simple: some people might think it is vindictive, revengeful or ad hominem. After reflecting about it for years, I have now decided to go ahead with it (sorry, it’s a bit lengthy). This case study is not meant to be vindictive, but offers an important insight into the power of conflicts of interest in SCAM that are not financial but ideological. I think it is crucial that people are aware of and consider such conflicts carefully, and I can’t see how else I might demonstrate my point so plainly.

Dr Adrian White was a co-worker of mine for about 10 years. He became a trusted colleague, my ‘right hand’ man and even my deputy at my Exeter department. When I discovered that my trust had been misplaced, I did not prolong his contract (I will not dwell on this episode, those who are interested find it in my memoir). Adrian then got a senior research fellowship with Prof John Campbell (not my favourite colleague at Exeter) at the department of general practice where he continued his research on acupuncture for about 10 more years largely unsupervised.

Adrian had been an acupuncturist body and soul (in fact, I had never before met anyone so utterly convinced of the value of this therapy). When he joined my team, he was scientifically naive, and we spent many month trying to teach him how to think like a scientist. Initially, he found it very difficult to think critically about acupuncture. Later, I thought the problem was under control. Yet, most of his research in my department was guided by me and tightly supervised (i.e. I made sure that out studies were testing rather than promoting SCAM, and that our reviews were critical assessments of the existing evidence).

Thus there exist two separate and well-documented periods of a pro-acupuncture researcher:

  • 10 years guided by me and members of my team;
  • 10 years largely unsupervised.

What could be more tempting than to compare Adrian’s output during these two periods?

To do this, I looked up all of Adrian’s 120 publications on acupuncture and selected those 52 articles that generated factual new data (mostly clinical trials or systematic reviews). As it happens, they are numerically distributed almost equally within the two periods. The endpoints for my analysis were the directions of the conclusions of his papers. I therefore extracted, dated, and rated the 52 articles as follows:

  • P = positive from the point of view of an acupuncture advocate,
  • N = negative from the point of view of an acupuncture advocate.
  • P/N = not clearly pointing in either direction.

To render this exercise transparent (occasionally, I was not entirely sure about my ratings), I copied all the 52 conclusions and provided links to the original papers so that anyone inferested is able to check easily.

Here are my findings. Articles 1 – 27 were published AFTER Adrian had left my department; articles 28 – 52 are his papers from the time while he worked with me.

  1. A definitive three-arm trial is feasible. Further follow-up reminders, minimum data collection and incentives should be considered to improve participant retention in the follow-up processes in the standardised advice and exercise booklet arm. (2016) P/N
  2. The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking. (2016) P
  3. The available results suggest that acupuncture is effective for treating frequent episodic or chronic tension-type headaches, but further trials – particularly comparing acupuncture with other treatment options – are needed. (2016) P
  4. Acupuncture during pregnancy appears to be associated with few AEs when correctly applied. (2014) P
  5. Although pooled estimates suggest possible short-term effects there is no consistent, bias-free evidence that acupuncture, acupressure, or laser therapy have a sustained benefit on smoking cessation for six months or more. However, lack of evidence and methodological problems mean that no firm conclusions can be drawn. Electrostimulation is not effective for smoking cessation. Well-designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions. (2014) P
  6. The current evidence suggests that acupuncture may have some effects on drug dependence that have been missed because of choice of outcome in many previous studies, and future studies should use outcomes suggested by clinical experience. Body points and electroacupuncture, used in the original clinical observation, justify further research. (2013) P
  7. Acceptability is very high and may be maximised by taking a number of factors into account: full information should be provided before treatment begins; flexibility should be maintained in the appointment system and different levels of contact between fellow patients should be fostered; sufficient space and staffing should be provided and single-sex groups used wherever possible. (2012) P
  8. This is the first evaluation of nurse-led group (multibed) acupuncture clinics for patients with knee osteoarthritis to include a 2 year follow-up. It shows the practicability of offering a low-cost acupuncture service as an alternative to knee surgery and the service’s success in providing long-term symptom relief in about a third of patients. Using realistic assumptions, the cost consequences for the local commissioning group are an estimated saving of £100 000 a year. Sensitivity analyses are presented using different assumptions. (2012) P
  9. There is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but lack of evidence and methodological problems mean that no firm conclusions can be drawn. Further, well designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions. (2011) P/N
  10. Eight (8) of 10 international acupuncture experts were able to reach consensus on the syndromes, symptoms, and treatment of postmenopausal women with hot flashes. The syndromes were similar to those used by practitioners in the ACUFLASH clinical trial, but there were considerable differences between the acupuncture points. This difference is likely to be the result of differences in approach of training schools, and whether it is relevant for clinical outcomes is not well understood. (2011) P
  11. 70% of those patients eligible to participate volunteered to do so; all participants had clinically identified MTrPs; a 100% completion rate was achieved for recorded self-assessment data; no serious adverse events were reported as a result of either intervention; and the end of treatment attrition rate was 17%. A phase III study is both feasible and clinically relevant. This study is currently being planned. (2010) P
  12. In conclusion, the results from all studies are in agreement with the hypothesis that acupuncture needling relieves hot flushes. There are few data however supporting the hypothesis that the effect of acupuncture is point specific. Future research should investigate whether there is a biological effect of needling on hot flushes or not, whether tailored treatment is superior to standardised treatment, and ways of delivering treatment that causes least discomfort and least cost. (2010) P
  13. Acupuncture can contribute to a more rapid reduction in vasomotor symptoms and increase in health-related quality of life in postmenopausal women but probably has no long-term effects. (2010) P
  14. within the context of this pilot study, the sham acupuncture intervention was found to be a credible control for acupuncture. This supports its use in a planned, definitive, randomised controlled trial on a similar whiplash injured population. (2009) N/P
  15. factors other than the TCM syndrome diagnoses and the point selection may be of importance regarding the outcome of the treatment. (2009) N/P
  16. Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women. (2009) P
  17. the authors conclude that acupuncture could be a valuable non-pharmacological tool in patients with frequent episodic or chronic tension-type headaches. (2009) P
  18. there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of ‘true’ acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment. (2009) P
  19. We have conducted the first survey of the effects of provision of acupuncture in UK general practice, using data provided by the NHS, and uncovered a wide variation in the availability of the service in different areas. We have been unable to demonstrate any consistent differences in the prescribing or referral rates that could be due to the use of acupuncture in these practices. The wide variation in the data means that if such a trend exists, a very large survey would be needed to identify it. However, we discovered inaccuracies and variations in presentation of data by the PCTs which have made the numerical input, and hence our results, unreliable. Thus the practicalities of access to data and the problems with data accuracy would preclude a nationwide survey. (2008) P
  20. In conclusion, there is limited evidence deriving from one study that deep needling directly into myofascial trigger points has an overall treatment effect when compared with standardised care. Whilst the result of the meta-analysis of needling compared with placebo controls does not attain statistically significant, the overall direction could be compatible with a treatment effect of dry needling on myofascial trigger point pain. However, the limited sample size and poor quality of these studies highlights and supports the need for large scale, good quality placebo controlled trials in this area. (2009) P
  21. We conclude that limited evidence supports acupuncture use in treating pregnancy-related pelvic and back pain. Additional high-quality trials are needed to test the existing promising evidence for this relatively safe and popular complementary therapy. (2008) P
  22. Acupuncture appears to offer symptomatic improvement to some patients with fibromyalgia in a tertiary clinic who have failed to respond to other treatments. In view of its safety, further acupuncture research is justified in this population. (2007) P
  23. It is speculated that optimal results from acupuncture treatment for osteoarthritis of the knee may involve: climatic factors, particularly high temperature; high expectations of patients; minimum of four needles; electroacupuncture rather than manual acupuncture, and particularly, strong electrical stimulation to needles placed in muscle; and a course of at least 10 treatments. These factors offer some support to criteria for adequate acupuncture used in the recent review. In addition, ethnic and cultural factors may influence patients’ reporting of their symptoms, and different versions of an outcome measure are likely to differ in their sensitivity – both factors which may lead to apparent rather than real differences between studies. The many variables in a study are likely to be more tightly controlled in a single centre study than in multicentre studies.  (2007) P
  24. Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested. (2007) P
  25. Auricular acupuncture appears to be effective for smoking cessation, but the effect may not depend on point location. This calls into question the somatotopic model underlying auricular acupuncture and suggests a need to re-evaluate sham controlled studies which have used ‘incorrect’ points. Further experiments are necessary to confirm or refute these observational conclusions. (2006) P
  26. Acupuncture that meets criteria for adequate treatment is significantly superior to sham acupuncture and to no additional intervention in improving pain and function in patients with chronic knee pain. Due to the heterogeneity in the results, however, further research is required to confirm these findings and provide more information on long-term effects. (2007) P
  27. There is no consistent evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but methodological problems mean that no firm conclusions can be drawn. Further research using frequent or continuous stimulation is justified. (2006) N/P
  28. Acupuncture is not superior to sham treatment for recovery in activities of daily living and health-related quality of life after stroke, although there may be a limited effect on leg function in more severely affected patients.  (2005) N
  29. The evidence from controlled trials is insufficient to conclude whether acupuncture is an effective treatment for depression, but justifies further trials of electroacupuncture. (2005) N
  30. Acupuncture effectively relieves chronic low back pain. No evidence suggests that acupuncture is more effective than other active therapies. (2005) N/P
  31. In view of the small number of studies and their variable quality, doubt remains about the effectiveness of acupuncture for gynaecological conditions. Acupuncture and acupressure appear promising for dysmenorrhoea, and acupuncture for infertility, and further studies are justified. (2003) N
  32.  In conclusion, the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and is inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. It is therefore a valid control for acupuncture trials. The findings also lend support to the existence of de qi, a major concept underlying traditional Chinese acupuncture. (2002) N/P
  33. There is no clear evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation. (2002) N
  34. Collectively, these data imply that acupuncture is superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo. (2002) N/P
  35. In conclusion, the incidence of adverse events following acupuncture performed by doctors and physiotherapists can be classified as minimal; some avoidable events do occur. Acupuncture seems, in skilled hands, one of the safer forms of medical intervention. (2001) N/P
  36. Based on the evidence of rigorous randomised controlled trials, there is no compelling evidence to show that acupuncture is effective in stroke rehabilitation. Further, better-designed studies are warranted. (2001) N
  37. Although it has already been demonstrated that severe adverse events seem to be uncommon in standard practice, many serious cases of negligence have been found in the present review, suggesting that training system for acupuncturists (including medical doctors) should be improved and that unsupervised self-treatment should be discouraged. (2001) N
  38. Direct needling of myofascial trigger points appears to be an effective treatment, but the hypothesis that needling therapies have efficacy beyond placebo is neither supported nor refuted by the evidence from clinical trials. Any effect of these therapies is likely because of the needle or placebo rather than the injection of either saline or active drug. Controlled trials are needed to investigate whether needling has an effect beyond placebo on myofascial trigger point pain. (2001) N/P
  39. Although the incidence of minor adverse events associated with acupuncture may be considerable, serious adverse events are rare. Those responsible for establishing competence in acupuncture should consider how to reduce these risks. (2001) N
  40. In conclusion, this study does not provide evidence that this form of acupuncture is effective in the prevention of episodic tension-type headache. (2000) N
  41. The present study provides no strong evidence to support the hypothesis that the acupuncture point SP6 is more tender in women and in men. Recommendations for further investigations are discussed.  (2000) N
  42. Acupuncture has not been demonstrated to be efficacious as a treatment for tinnitus on the evidence of rigorous randomized controlled trials. (2000) N
  43. We conclude that acupuncture continues to be associated with occasional, serious adverse events and fatalities. These events have no geographical limits. Most of these events are due to negligence. Everyone concerned with setting standards, delivering training, and maintaining competence in acupuncture should familiarise themselves with the lessons to be learnt from these untoward events. (2000) N
  44. Overall, the existing evidence suggests that acupuncture has a role in the treatment of recurrent headaches. However, the quality and amount of evidence is not fully convincing. There is urgent need for well-planned, large-scale studies to assess effectiveness and efficiency of acupuncture under real life conditions. (1999) N/P
  45. While the frequency of adverse effects of acupuncture is unknown and they may be rare, knowledge of normal anatomy and anatomical variations is essential for safe practice and should be reviewed by regulatory bodies and those responsible for training courses. (1999) N
  46.  In conclusion, the hypothesis that acupuncture is efficacious in the treatment of neck pain is not based on the available evidence from sound clinical trials. Further studies are justified. (1999) N
  47. Even though all studies are in accordance with the notion that acupuncture is effective for temporomandibular joint dysfunction, this hypothesis requires confirmation through more rigorous investigations. (1999) N
  48. Acupuncture is not free of risks. All adverse events reported in 1997 would have been avoidable. The absolute number of cases is small, but the degree of underreporting remains unknown. (1999) N
  49. This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms. (1998) N
  50. Acupuncture was shown to be superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo. (1998) N/P
  51. Considerable variation was observed in the scores awarded by the acupuncture experts. (1998) N
  52. It is therefore concluded that, according to the data published to date, the evidence that acupuncture is a useful adjunct for stroke rehabilitation is encouraging but not compelling. More and better trials are required to clarify this highly relevant issue. (1996) N

The results are remarkable (particularly considering that one would not expect unbiased studies or reviews of acupuncture to generate plenty of positive conclusions):

0 times N, 5 times N/P, 22 times P – after Adrian had left my department,

17 times N, 7 times N/P, 0 times P – while Adrian worked in my department.

From these figures, it is tempting to calculate the ratios for both periods of negative : positive conclusions:

zero versus infinite

If that is not impressive, I don’t know what is!

Looking just at the positive and the negative papers over the years:

One could discuss these papers in more detail, but I think this is hardly necessary. Just a few highlights perhaps: look at articles No 5, 20 and 27 for examples of turning an essentially negative finding into a positive conclusion. Notice that Adrian conducted a clinical trial of acupuncture for smoking cessation (No 49) while working with me and later published uncritical positive reviews on the subject. Does this not indicate that he distrusted his own study because it had not generated the result he had hoped for?

Of course, my analysis is merely a case study and therefore my findings are not generalisable. However, in my personal experience, the described phenomenon is by no means an exception in SCAM research. I have observed similar phenomena over and over again. Just look at the ALTERNATIVE MEDICINE HALL OF FAME that I created for this blog:

But Adrian’s case might be unique because it allows us to make a longitudinal observation over two decades. And it suggests to me that an ideological bias can (and often is) so strong and indistructable that is re-emerges as soon as it is no longer kept under strict control.

I have long suspected that ideological conflicts of interest have a much more powerful influence in SCAM research than financial ones. Such an overpowering influence might even be characteristic to much of SCAM research. And because it can be so dominant, it seems important to know about. People reading research need to be aware that it originates from a biased source, and funders who finance research would be wise to think twice about supporting researchers who are likely to generate findings that are biased and therefore false-positive. In the final analysis, such research is worse than no research at all.

This systematic review and meta-analysis was aimed at investigating the effect and safety of acupuncture for the treatment of chronic spinal pain.

The authors included 22 randomized controlled trials (RCTs) involving patients with chronic spinal pain treated by acupuncture versus sham acupuncture, no treatment, or another treatment were included. Chronic spinal pain was defined as:

  • chronic neck pain,
  • chronic low back pain,
  • or sciatica for more than 3 months.

Fourteen studies had a high risk of bias, 5 studies had a low risk of bias, and 5 studies had an unclear risk of bias. Pooled analysis revealed that:

  • acupuncture can reduce chronic spinal pain compared to sham acupuncture (weighted mean difference [WMD]  -12.05, 95% confidence interval [CI] -15.86 to -8.24),
  • acupuncture can reduce chronic spinal pain compared to mediation control (WMD -18.27, 95% CI -28.18 to -8.37),
  • acupuncture can reduce chronic spinal pain compared to usual care control (WMD -9.57, 95% CI -13.48 to -9.44),
  • acupuncture can reduce chronic spinal pain compared to no treatment control (WMD -17.10, 95% CI -24.83 to -9.37).

In terms of functional disability, acupuncture can improve physical function at

  • immediate-term follow-up (standardized mean difference [SMD] -1.74, 95% CI -2.04 to -1.44),
  • short-term follow-up (SMD -0.89, 95% CI -1.15 to -0.62),
  • long-term follow-up (SMD -1.25, 95% CI -1.48 to -1.03).

Trials assessed as having a high risk of bias (WMD −13.45, 95% CI −17.23 to −9.66, I 2 96.2%, moderate-quality evidence, including 14 studies and 1379 patients) found greater effects of acupuncture treatment than trials assessed as having a low risk of bias (WMD −11.99, 95% CI −13.94 to −10.03, I 2 44.6%, high-quality evidence, including 4 studies and 432 patients), but smaller effects than trials assessed as having an unclear risk of bias (WMD −14.51, 95% CI −17.25 to −11.78, I 2 0%, high-quality evidence, including 3 studies and 190 patients).

Only 6 trials provided information on adverse events. No trial reported data on serious adverse events during acupuncture treatment. The most frequent adverse events were temporarily worsened pain and needle pain at the acupuncture site, which can decrease quickly after a short period of rest.

The authors concluded that compared to no treatment, sham acupuncture, or conventional therapy such as medication, massage, and physical exercise, acupuncture has a significantly superior effect on the reduction in chronic spinal pain and function improvement. Acupuncture might be an effective treatment for patients with chronic spinal pain and it is a safe therapy.

I think this is a thorough review which produced interesting findings. I agree with most of what the authors report, except with their conclusions which I find too optimistic. In view of the facts that

  • only 5 RCTs had a low risk of bias,
  • collectively, the rigorous trials reported smaller effect sizes,
  • the majority of trials failed to mention adverse effects which, in my view, casts considerable doubt on their quality and ethical standard,

I would have phrased the conclusion differently: compared to no treatment, sham acupuncture, or conventional therapies, acupuncture seems to have a significantly superior effect on pain and function. Due to the lack rigour of most studies, these effects are less certain than one would have wished. Many trials fail to report adverse effects which reflects poorly on their quality and ethics and prevents conclusions about the safety of acupuncture. In essence, this means that the effectiveness and safety of acupuncture as a treatment of chronic spinal pain remains uncertain.

Acupuncture-moxibustion therapy (AMT) is a so-called alternative medicine (SCAM) that has been used for centuries in treatment of numerous diseases. Some enthusiasts even seem to advocate it for chemotherapy-induced leukopenia (CIL)  The purpose of this review was to evaluate the efficacy and safety of acupuncture-moxibustion therapy in treating CIL.

Relevant studies were searched in 9 databases up to September 19, 2020. Two reviewers independently screened the studies for eligibility, extracted data, and assessed the methodological quality of selected studies. Meta-analysis of the pooled mean difference (MD) and risk ratio (RR) with their respective 95% confidence intervals (CI) were calculated.

Seventeen studies (1206 patients) were included, and the overall quality of the included studies was moderate. In comparison with medical therapy, AMT has a better clinical efficacy for CIL (RR, 1.24; 95% CI, 1.17-1.32; P < 0.00001) and presents advantages in increasing leukocyte count (MD, 1.10; 95% CI, 0.67-1.53; P < 0.00001). Also, the statistical results show that AMT performs better in improving the CIL patients’ Karnofsky performance score (MD, 5.92; 95% CI, 3.03-8.81; P < 0.00001).

The authors concluded that this systematic review and meta-analysis provides updated evidence that AMT is a safe and effective alternative for the patients who suffered from CIL.

A CIL is a serious complication. If I ever were afflicted by it, I would swiftly send any acupuncturist approaching my sickbed packing.

But this is not an evidence-based attitude!!!, I hear some TCM-fans mutter. What more do you want that a systematic review showing it works?

I beg to differ. Why? Because the ‘evidence’ is hardly what critical thinkers can accept as evidence. Have a look at the list of the primary studies included in this review:

  1. Lin Z. T., Wang Q., Yu Y. N., Lu J. S. Clinical observation of post-chemotherapy-leukopenia treated with ShenMai injectionon ST36. World Journal of Integrated Traditional and Western Medicine2010;5(10):873–876. []
  2. Wang H. Clinical Observation of Acupoint Moxibustion on Leukopenia Caused by Chemotherapy. Beijing, China: Beijing University of Chinese Medicine; 2011. []
  3. Fan J. Y. Coupling of Yin and Yang between Ginger Moxibustion Improve the Clinical Effect of the Treatment of Chemotherapy Adverse Reaction. Henan, China: Henan University of Chinese Medicine; 2013. []
  4. Lu D. R., Lu D. X., Wei M., et al. Acupoint injection with addie injection for patients of nausea and vomiting with cisplatin induced by chemotherapy. Journal of Clinical Acupuncture and Moxibustion2013;29(10):33–38. []
  5. Yang J. E. The Clinical Observation on Treatment of Leukopenia after Chemotherapy with Needle Warming Moxibustion. Hubei, China: Hubei University of Chinese Medicine; 2013. []
  6. Fu Y. H., Chi C. Y., Zhang C. Y. Clinical effect of acupuncture and moxibustion on leukopenia after chemotherapy of malignant tumor. Guide of China Medicine2014;12(12) []
  7. Wang J. N., Zhang W. X., Gu Q. H., Jiao J. P., Liu L., Wei P. K. Protection of herb-partitioned moxibustion on bone marrow suppression of gastric cancer patients in chemotherapy period. Chinese Archives of Traditional Chinese Medicine2014;32(12):110–113. []
  8. Zhang J. The Clinical Research on Myelosuppression and Quality of Life after Chemotherapy Treated by Grain-Sized Moxibustion. Nanjing, China: Nanjing University of Chinese Medicine; 2014. []
  9. Tian H., Lin H., Zhang L., Fan Z. N., Zhang Z. L. Effective research on treating leukopenia following chemotherapy by moxibustion. Clinical Journal of Chinese Medicine2015;7(10):35–38. []
  10. Hu G. W., Wang J. D., Zhao C. Y. Effect of acupuncture on the first WBC reduction after chemotherapy for breast cancer. Beijing Journal of Traditional Chinese Medicine2016;35(8):777–779. []
  11. Zhu D. L., Lu H. Y., Lu Y. Y., Wu L. J. Clinical observation of Qi-blood-supplementing needling for leukopenia after chemotherapy for breast cancer. Shanghai Journal of Acupuncture and Moxibustion2016;35(8):964–966. []
  12. Chen L, Xu G. Y. Observation on the prevention and treatment of chemotherapy-induced leukopenia by moxibustion therapy. Zhejiang Journal of Traditional Chinese Medicine2016;51(8):p. 600. []
  13. Mo T., Tian H., Yue S. B., Fan Z. N., Zhang Z. L. Clinical observation of acupoint moxibustion on leukocytopenia caused by tumor chemotherapy. World Chinese Medicine2016;11(10):2120–2122. []
  14. Nie C. M. Nursing observation of acupoint moxibustion in the treatment of leucopenia after chemotherapy. Today Nurse2017;4:93–95. []
  15. Wang D. Y. Clinical Research on Post-chemotherapy-leukopenia with Spleen-Kidney Yang Deficiency in Colorectal Cancer Treated with Point-Injection. Yunnan, China: Yunnan University of Chinese Medicine; 2017. []
  16. Gong Y. Q, Zhang M. Q, Zhang B. C. Prevention and treatment of leucocytopenia after chemotherapy in patients with malignant tumor with ginger partitioned moxibustion. Chinese Medicine Modern Distance Education of China2018;16(21):135–137. []
  17. Li Z. C., Lian M. J., Miao F. G. Clinical observation of fuzheng moxibustion combined with wenyang shengbai decoction in the treatment of 80 cases of leukopenia after chemotherapy. Hunan Journal of Traditional Chinese Medicine2019;35(3):64–66. []

Notice anything peculiar?

  • The studies are all from China where data fabrication was reported to be rife.
  • They are mostly unavailable for checking (why the published adds links that go nowhere is beyond me).
  • Many do not look at all like randomised clinical trials (which, according to the authors, was an inclusion criterion).
  • Many do not look as though their primary endpoint was the leukocyte count (which, according to the authors, was another inclusion criterion).

Intriguingly, the authors conclude that AMT is not just effective but also ‘safe’. How do they know? According to their own data extraction table, most studies failed to mention adverse effects. And how exactly is acupuncture supposed to increase my leukocyte count? Here is what the authors offer as a mode of action:

Based on the theory of traditional Chinese medicine (TCM), CIL belongs to the category of consumptive disease, owing to the exhaustion of genuine qi in the zang-fu viscera and the insufficiency of kidney essence and qi-blood. Researchers believe that there is an intimate association between the occurrence of malignant tumors and the deficiency of genuine qi. During attacking the cancer cells, chemotherapeutics also damaged the function of zang-fu viscera and qi-blood, leading to CIL. According to the theory of TCM and meridian, acupuncture-moxibustion is an ancient therapeutic modality that may be traced back more than 3500 years in China. Through meridian conduction, acupuncture-moxibustion therapy stimulates acupoints to strengthen the condition of zang-fu viscera and immune function, supporting genuine qi to improve symptoms of consumption.

I think it is high time that we stop tolerating that the medical literature gets polluted with such nonsense (helped, of course, by journals that are beyond the pale) – someone might actually believe it, in which case it would surely hasten the death of vulnerable patients.

There is some encouraging evidence regarding the positive influence of vitamin D on COVID-19. But is it convincing? Is it causal? As always, it is worth looking at the totality of the reliable evidence.

In this systematic review and meta-analysis, the researchers analyze the association between vitamin D deficiency and COVID-19 severity. They conducted an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases—Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19.

The researchers identified 1542 articles and 27 met their inclusion criteria. The results show that

  • vitamin D deficiency was not associated with a higher chance of infection by COVID-19,
  • severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases,
  • vitamin D concentration insufficiency increased hospitalization and mortality rates,
  • There was a positive association between vitamin D deficiency and the severity of the disease.

The authors concluded that the results of the meta-analysis confirm the high prevalence of vitamin D deficiency in people with COVID-19, especially the elderly. We should add that vitamin D deficiency was not associated with COVID-19 infection. However, we observed a positive association between vitamin D deficiency and the severity of the disease. From this perspective, evaluating blood vitamin D levels could be considered in the clinical practice of health professionals. Moreover, vitamin D supplementation could be considered in patients with vitamin D deficiency and insufficiency, if they have COVID-19. However, there is no support for supplementation among groups with normal blood vitamin D values with the aim of prevention, prophylaxis or reducing the severity of the disease.

These are interesting findings, no doubt. They relate to associations, as the authors repeatedly stress in the text of the paper. They do not, however, signify cause and effect relationships. The principal outcome of this research should be a hypothesis that subsequently needs testing in clinical trials.

So, why on earth did the authors chose that seriously misleading title of their paper? It clearly implies a causal effect; and this can only be verified by conducting clinical trials. One such study has been published (as discussed here) and it concluded that administration of calcifediol may improve the clinical outcome of subjects requiring hospitalization for COVID-19.

My conclusion: it seems well worth conducting more and more rigorous clinical trials.

Melatonin is an indolamine hormone which is secreted from the human pineal gland during night-time acting as physiological regulator. In many countries, dietary supplements containing synthetically produced melatonin are available. Melatonin is being promoted as a treatment of a range of conditions, including virtually all types of cancer.

One website, for instance, states that the anti-cancer benefits of melatonin aren’t just indirect; this miracle molecule is also classified as a directly cytotoxic hormone and anti-cancer agent. Studies have referred to melatonin as a “full-service anti-cancer agent” due to its ability to inhibit the initiation of cell mutation and cancer growth, and to halt the progression and metastasis of cancer cell colonies.

Such statements sound far too good to be true. So, let’s have a look and find out what the evidence tells us. Test-tube experiments suggest that melatonin has anti-cancer effects.[1] Its actions include the advancement of apoptosis, the arrest of the cell cycle, inhibition of metastasis, and antioxidant activity.[2]

A review of 21 clinical trials of melatonin for cancer found positive effects for complete response, partial response, and stable disease. In trials combining melatonin with chemotherapy, adjuvant melatonin therapy decreased 1-year mortality and improved outcomes of complete response, partial response, and stable disease. In these studies, melatonin also significantly reduced asthenia, leukopenia, nausea and vomiting, hypotension, and thrombocytopenia. The authors concluded that melatonin may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.[3]

A further systematic review of RCTs of melatonin in solid tumour cancer patients evaluated its effect on one-year survival. Ten trials were included of melatonin as either sole treatment or as adjunct treatment. Melatonin reduced the risk of death at 1 year. Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported.[4]

A 2012 systematic review confirmed these findings by concluding that Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.[5]

Finally, a 2020 review concluded that melatonin in combination with anticancer agents may improve the efficacy of routine medicine and survival rate of patients with cancer. [6] Apart from its direct anticancer potential, melatonin also seems to reduce chemotherapy toxicity, while improving its therapeutic efficacy.[7]

So, is this evidence compelling? While all this does indeed sound encouraging, it is necessary to mention several important caveats:

  • The primary studies of melatonin suffer from several methodological shortcomings.
  • Their vast majority originate from one single research group.
  • In recent years, there have been no further clinical studies trying to replicate the initial findings.

This means that definitive trials are still missing, and it would seem wise to interpret the existing evidence with great caution.

References

[1] Kong X, Gao R, Wang Z, Wang X, Fang Y, Gao J, Reiter RJ, Wang J. Melatonin: A Potential Therapeutic Option for Breast Cancer. Trends Endocrinol Metab. 2020 Sep 3:S1043-2760(20)30155-7. doi: 10.1016/j.tem.2020.08.001. Epub ahead of print. PMID: 32893084.

[2] Samanta S. Melatonin: an endogenous miraculous indolamine, fights against cancer progression. J Cancer Res Clin Oncol. 2020 Aug;146(8):1893-1922. doi: 10.1007/s00432-020-03292-w. Epub 2020 Jun 24. PMID: 32583237.

[3] Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012 Dec;11(4):293-303. doi: 10.1177/1534735411425484. Epub 2011 Oct 21. PMID: 22019490.

[4] Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6. doi: 10.1111/j.1600-079X.2005.00258.x. PMID: 16207291.

[5] Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-20. doi: 10.1007/s00280-012-1828-8. Epub 2012 Jan 24. PMID: 22271210.

[6] Pourhanifeh MH, Mehrzadi S, Kamali M, Hosseinzadeh A. Melatonin and gastrointestinal cancers: Current evidence based on underlying signaling pathways. Eur J Pharmacol. 2020 Nov 5;886:173471. doi: 10.1016/j.ejphar.2020.173471. Epub 2020 Aug 30. PMID: 32877658.

[7] Iravani S, Eslami P, Dooghaie Moghadam A, Moazzami B, Mehrvar A, Hashemi MR, Mansour-Ghanaei F, Mansour-Ghanaei A, Majidzadeh-A K. The Role of Melatonin in Colorectal Cancer. J Gastrointest Cancer. 2020 Sep;51(3):748-753. doi: 10.1007/s12029-019-00336-4. PMID: 31792737.

Some of us got used to the idea that acupuncture might be effective for pain. But could it work for infections? Unlikely! Well, let’s not rely on gut feelings; let’s have a fair and critical look at the evidence.

This systematic review assessed the evidence for acupuncture for uncomplicated recurrent urinary tract infections (rUTI) women. Five randomised controlled trials (RCTs) evaluating the effects of acupuncture and related therapies for prophylaxis or treatment of uncomplicated rUTI in women were included. The methodological quality of the studies and the strength of the evidence were low to moderate. The chance of achieving a composite cure with acupuncture therapies was greater than that with antibiotics (three studies, 170 participants, RR 1.92, 95% CI 1.31‐2.81, I2 = 38%). The risk of UTI recurrence was lower with acupuncture than with no treatment (two studies, 135 participants, RR 0.39, 95% CI 0.26–0.58, I2 = 0%) and sham acupuncture (one study, 53 participants, RR 0.45, 95% CI 0.22–0.92).

The authors concluded that acupuncture showed promising results compared to no treatment and sham acupuncture in reducing recurrence, based on low to moderate certainty evidence. Low certainty evidence found acupuncture increased the chance of achieving a composite cure compared to antibiotics. Findings from this review should be interpreted with caution, taking into consideration the biases identified and small sample size of the included trials. Included studies suggest acupuncture has a good safety profile for women with UTI, and may be considered as a therapeutic option in the treatment and prevention of rUTI in women, particularly those who are unresponsive to, or intolerant of, antibiotics. Rigorously designed research is needed to inform clinical decisionmaking about the use of acupuncture for women with UTIs.

The authors of this review are affiliated to the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangdong Provincial Academy of Chinese Medical Sciences and The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China and the China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia. The review was funded by the China-Australia International Research Centre for Chinese Medicine (CAIRCCM) (International Cooperation Project, Grant Number 2012DFA31760), and the National Natural Science Foundation of China (NSFC) (Grant Number 81873261). In view of these facts, it is strange, I think, that the authors declared no conflicts of interest.

The 5 primary studies included in this review are the following:

    1. Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the
      prevention of uncomplicated recurrent lower urinary tract infections in adult women. American journal of
      public health. 2002;92(10):1609-11.
    2. Aune A, Alraek T, LiHua H, Baerheim A. Acupuncture in the prophylaxis of recurrent lower urinary
      tract infection in adult women. Scandinavian journal of primary health care. 1998;16(1):37-9.
    3. Hong JY, Li F, Liang XQ, Hou Z. [Efficacy observation on female chronic pyelonephritis treated with
      abdominal cluster-needling therapy]. Zhongguo zhen jiu = Chinese acupuncture & moxibustion.
      2013;33(4):303-5.
    4. Yu SM, Guo DD. Moxibustion combined with antibiotics was used to treat 30 cases of chronic
      urinary tract infection in adult women. Shandong Journal of Traditional Chinese Medicine.
      2010;29(09):621-2.
    5. Liu JL, Luo Q, Liu XH, Lin L. Observation on the clinical effect of external treatment of strong renal
      moxibustion on recurrent urinary tract infection. China Modern Doctor. 2018;56(29):116-8.

As always, it is worth checking these studies for reliability.

In the trial by Alraek et al patients were randomised patients to receive either acupuncture or no treatment. Is anyone surprised that the former group fared better than the latter? (I am not!)

The trial by Aune et al is the only study that attempted to control for placebo effects by using a sham control group. This is what they used as a sham treatment: 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 controls have the purpose of rendering patients unaware whether they receive the real or the sham treatment. The method used here cannot achieve this aim; patients were easily able to determine that they were in the control group.

The last three trials are all not Medline-listed studies authored by Chinese investigators published in inaccessible journals in Chinese. We know that such studies invariably report positive outcomes which are often fabricated and thus have a reliability close to zero. But even if we ignore these facts for a moment, from what I see in the results table of the review, these studies are invalid. All three are equivalence trials of acupuncture versus antibiotics; with a sample size of merely around 30, they must be woefully underpowered and thus unable to generate a reliable result.

The authors of this review claim that the risk of bias of trials was generally high or unclear. This is an understatement to put it mildly. In fact, the quality of the studies was mostly dismal.

In view of all this, I take the liberty to re-formulate the conclusions drawn by the review authors as follows:

Due to the lack of reliable RCTs, the effectiveness of acupuncture as a treatment or prevention of rUTIs remains unproven. Due to the implausibility of the therapy, its effectiveness seems highly unlikely.

PS

The BJOG should never have published such a deeply misleading paper.

Researchers from the Department of Physiotherapy, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India, and the Mother Teresa Saket College of Physiotherapy, Saket, Panchkula, Haryana, India, have just published a systematic review which is remarkable in several ways. Let me therefore present to you the abstract unaltered:

Background: Spinal pain or misalignment is a very common disorder affecting a significant number of populations resulting in substantial disability and economic burden. Various manual therapeutic techniques such as spinal manipulations and mobilizations can be used to treat and manage pain and movement dysfunctions such as spinal mal-alignments and associated complications. These manual therapeutic techniques can affect the cardiovascular parameters.

Objective: The objective of this systematic review and meta-analysis is to assess the effect of spinal manipulation and mobilization on cardiovascular parameters.

Methods: We conducted a systematic review and meta-analysis to assess the effects of spinal mobilization and manipulation on cardiovascular responses. Mean changes in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Heart Rate (HR) were primary outcome measures. RevMan 5.3 software was used for the meta-analyses. Quality of the included studies was assessed by PEDro Rating scale. Risk of bias was assessed by Cochrane collaboration tool of risk of bias.

Results: Results of meta-analysis showed that there was statistically significant decrease in SBP ( MD=-4.56 , 95% CI=-9.20 , 0.08; p≤0.05 ) with moderate heterogeneity ( I2=75% , p<0.0002 ) in experimental group as compared to control group. There was statistically non-significant decrease in DBP ( MD=-1.96 , 95% CI=-4.60 , 0.69; p=0.15 ) with high heterogeneity ( I2=91% , p<0.00001 ), Change HR was statistically non-significant ( MD=-0.24 , 95% CI=-3.59 , 3.11; p=0.89 ) with moderate heterogeneity ( I2=60% , p=0.01 ). Exclusion of short duration studies in sensitivity analysis revealed a statistically significant change in DBP ( MD=-0.94 , 95% CCI=-1.85 , -0.03 ; p=0.04 ). However, the result was statistically non-significant for HR after sensitivity analysis.

Conclusion: Spinal manipulations and mobilizations may result in significant decrease of systolic as well as diastolic Blood Pressure.

After reading the full paper, I was uncertain whether to laugh or to cry. Then I decided for the former option.

Any paper that starts with the statement ‘spinal pain or misalignment is a very common disorder affecting a significant number of populations resulting in substantial disability and economic burden‘ can only be a hoax! In case you are uncertain about the reason of my amusement: spinal pain is not the same as spinal misalignment, and spinal misalignment (in the sense it is used here) is the figment of the imagination of a 18 carat charlatan called DD Palmer.

The rest of the article offers more superb hilarity: the authors write, for instance, that spinal malalignments (such as scoliosis) are mainly caused by body’s abnormal posture, asymmetries in bone growth and abnormalities of neuromuscular system. Scoliosis is an abnormal lateral curvature of the spine, not a spinal malalignment and certainly not one that can be treated with spinal manipulation.

Then the authors state that spinal pain and malalignment mainly occur due to structure deterioration, altered biomechanics and abnormal posture. Workplace physical and psychosocial factors, emotional problems, smoking, poor job satisfaction, awkward posture and poor work environment can be the possible risk factors for spinal pain and malalignment. This leads to various musculoskeletal, psychosomatic, cardiovascular and respiratory dysfunctions which affect the functional capacity of the patient as well as quality of life. Oh really?

So, the findings of the authors’ meta-analysis do suggest a tiny effect on blood pressure.

Compared to what?

In the paper, the review authors repeatedly try to make us believe it is compared to placebo. However, this is not true; mostly it was compared to no treatment.

Was the hypotensive effect verified in hypertensive patients?

No, it was measured mostly in healthy volunteers.

Is the effect clinically relevant?

No, I don’t think so!

Is it comparable to or better than the one achievable with established treatments for hypertension?

No! In fact it is much smaller.

Does that bother the authors?

No, on the contrary, they state that in this meta-analysis, spinal manipulation and mobilization resulted in statistically significant reduction in SBP. Therefore, it can be used as an adjuvant therapy for the management of hypertension.

Were the studies using spinal manipulation as an adjuvant therapy?

No, mostly not.

Is the effect lasting long enough to be relevant for the management of hypertension?

No.

I better stop here because already my whole body hurts from laughing so much. Please, do read the full text, if you are in need of some comic relief.

And, I almost forgot: many thanks to the Indian researchers for this hilarious hoax!

Or did you perhaps mean all that seriously?

About one in three individuals have elevated blood pressure. This is bad news because hypertension is one of the most important risk factors for cardiovascular events like strokes and heart attacks. Luckily, there are many highly effective approaches for treating elevated blood pressure (diet, life-style, medication, etc.), and the drug management of hypertension has improved over the last few decades.

But unfortunately all anti-hypertensive drugs have side-effects and some patients look towards so-called alternative medicine (SCAM) to normalise their blood pressure. Therefore, we have to ask: are SCAMs effective treatments for hypertension? Because of the prevalence of hypertension, this is a question of great importance for public health.

In 2005, I addressed the issue by publishing a review entitled ‘Complementary/alternative medicine for hypertension: a mini-review‘. Here is its abstract:

Many hypertensive patients try complementary/alternative medicine for blood pressure control. Based on extensive electronic literature searches, the evidence from clinical trials is summarised. Numerous herbal remedies, non-herbal remedies and other approaches have been tested and some seem to have antihypertensive effects. The effect size is usually modest, and independent replications are frequently missing. The most encouraging data pertain to garlic, autogenic training, biofeedback and yoga. More research is required before firm recommendations can be offered.

Since the publication of this paper, more systematic reviews have become available. In order to get an overview of this evidence, I conducted a few simple Medline searches for systematic reviews (SRs) of SCAM published between 2005 and today. I included only SRs that were focussed on just one specific therapy as a treatment of just one specific condition, namely hypertension (omitting SRs with titles such as ‘Alternative treatments for cardiovascular conditions’). Reviews on prevention were also excluded. Here is what I found (the conclusions of each SR is quoted verbatim):

  1. A 2020 SR of auricular acupressure including 18 RCTs: The results demonstrated a favorable effect of auricular acupressure to reduce blood pressure and improve sleep in patients with hypertension and insomnia. Further studies to better understand the acupoints and intervention times of auricular acupressure are warranted.
  2. A 2020 SR of Chinese herbal medicines (CHM) including 30 studies: CHM combined with conventional Western medicine may be effective in lowering blood pressure and improving vascular endothelial function in patients with hypertension.
  3. A 2020 SR of Tai chi including 28 RCTs: Tai Chi could be recommended as an adjuvant treatment for hypertension, especially for patients less than 50 years old.
  4. A 2020 SR of Tai chi including 13 trials: Tai chi is an effective physical exercise in treating essential hypertension compared with control interventions.
  5. A 2020 SR of Tai chi including 31 controlled clinical trials: Tai Ji Quan is a viable antihypertensive lifestyle therapy that produces clinically meaningful BP reductions (i.e., 10.4 mmHg and 4.0 mmHg of SBP and DBP reductions, respectively) among individuals with hypertension.
  6. A 2020 SR of pycnogenol including 7 trials:  the present meta-analysis does not suggest any significant effect of pycnogenol on BP.
  7. A 2019 SR of Policosanol including 19 studies: Policosanol could lower SBP and DBP significantly; future long term studies are required to confirm these findings in the general population.
  8. A 2019 SR of dietary phosphorus including 14 studies: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association.
  9. A 2019 SR of ginger including 6 RCTs: ginger supplementation has favorable effects on BP.
  10. A 2019 SR of corn silk tea (CST) including 5 RCTs: limited evidence showed that CST plus antihypertensive drugs might be more effective in lowering blood pressure compared with antihypertensive drugs alone.
  11. A 2019 SR of blood letting including 7 RCTs: no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design, significant heterogeneity, and insufficient clinical data.
  12. A 2019 SR of Xiao Yao San (XYS) including 17 trials: XYS adjuvant to antihypertensive drugs maybe beneficial for hypertensive patients in lowering BP, improving depression, regulating blood lipids, and inhibiting inflammation.
  13. A 2019 SR of Chinese herbal medicines including 9 RCTs: Chinese herbal medicine as complementary therapy maybe beneficial for postmenopausal hypertension.
  14. A 2019 Cochrane review of guided imagery including 2 trials: There is insufficient evidence to inform practice about the use of guided imagery for hypertension in pregnancy.
  15. A 2019 Cochrane review of acupuncture including 22 RCTs: At present, there is no evidence for the sustained BP lowering effect of acupuncture that is required for the management of chronically elevated BP.
  16. A 2019 SR of wet cupping including 7 RCTs: no firm conclusions can be drawn and no clinical recommendations made.
  17. A 2019 SR of transcendental meditation (TM) including 9 studies: TM was associated with within-group (but not between-groups) improvements in BP.
  18. A 2019 SR of yoga including 49 trials: yoga is a viable antihypertensive lifestyle therapy that produces the greatest BP benefits when breathing techniques and meditation/mental relaxation are included.
  19. A 2018 SR of mindfulness-based stress reduction (MBSR) including 5 studies: The MBSR program is a promising behavioral complementary therapy to help people with hypertension lower their blood pressure
  20. A 2018 SR of beetroot juice (BRJ) including 11 studies: BRJ supplementation should be promoted as a key component of a healthy lifestyle to control blood pressure in healthy and hypertensive individuals.
  21. A 2018 SR of taurine including 7 studies: ingestion of taurine at the stated doses and supplementation periods can reduce blood pressure to a clinically relevant magnitude, without any adverse side effects.
  22. A 2018 SR of acupuncture including 30 RCTs: there is inadequate high quality evidence that acupuncture therapy is useful in treating hypertension.
  23. A 2018 SR of co-enzyme Q10 including 17 RCTs: CoQ10 supplementation may result in reduction in SBP levels, but did not affect DBP levels among patients with metabolic diseases.
  24. A 2018 SR of a traditional Chinese formula Longdanxiegan decoction (LDXGD) including 9 trials: Due to poor methodological quality of the included trials, as well as potential reporting bias, our review found no conclusive evidence for the effectiveness of LDXGD in treating hypertension.
  25. A 2018 SR of viscous fibre including 22 RCTs: Viscous soluble fiber has an overall lowering effect on SBP and DBP.
  26. A 2017 SR of yoga breathing exercise (pranayama) including 13 studies: The pranayama’s effect on BP were not robust against selection bias due to the low quality of studies. But, the lowering BP effect of pranayama is encouraging.
  27. A 2017 SR of dietary nitrate supplementation including 13 trials: Positive effects of medium-term dietary nitrate supplementation on BP were only observed in clinical settings, which were not corroborated by more accurate methods such as 24-h ambulatory and daily home monitorings.
  28. A 2017 SR of Vitamin D supplementation including 8 RCTs: vitamin D is not an antihypertensive agent although it has a moderate SBP lowering effect.
  29. A 2017 SR of pomegranate including 8 RCTs: The limited evidence from clinical trials to date fails to convincingly show a beneficial effect of pomegranate on blood pressure
  30. A 2017 SR of ‘forest bathing’ including 20 trials:  This systematic review shows a significant effect of Shinrin-yoku on reduction of blood pressure.
  31. A 2017 SR of Niuhuang Jiangya Preparation (NHJYP) including 12 RCTs: Our review indicated that NHJYP has some beneficial effects in EH patients with liver-yang hyperactivity and abundant phlegm-heat syndrome.
  32. A 2017 SR of Chinese medicines (CM) including 24 studies: CM might be a promising approach for the elderly with isolated systolic hypertension, while the evidence for CM employed alone was insufficient.
  33. A 2017 SR of beetroot juice including 22 RCTs: Our results demonstrate the blood pressure-lowering effects of beetroot juice and highlight its potential NO3-independent effects.
  34. A 2017 SR of blueberry including 6 RCTs: the results from this meta-analysis do not favor any clinical efficacy of blueberry supplementation in improving BP
  35. A 2016 Cochrane review of co-enzyme Q10 including 3 RCTs: This review provides moderate-quality evidence that coenzyme Q10 does not have a clinically significant effect on blood pressure.
  36. A 2016 SR of Nigella sativa including 11 RCTs: short-term treatment with N. sativa powder can significantly reduce SBP and DBP levels.
  37. A 2016 SR of vitamin D3 supplementation including 30 RCTs: Supplementation may be beneficial at daily doses >800 IU/day for <6 months in subjects ≥50 years old.
  38. A 2016 SR of anthocyanin supplementation including 6 studies: results from this meta-analysis do not favor any clinical efficacy of supplementation with anthocyanins in improving blood pressure.
  39. A 2016 SR of flaxseed including 15 trials: This meta-analysis of RCTs showed significant reductions in both SBP and DBP following supplementation with various flaxseed products.
  40. A 2016 SR of massage therapy including 9 RCTs: This systematic review found a medium effect of massage on SBP and a small effect on DBP in patients with hypertension or prehypertension.
  41. A 2015 SR of massage therapy including 24 studies: There is some encouraging evidence of massage for essential hypertension.
  42. A 2015 SR of transcendental meditation (TM) including 12 studies: an approximate reduction of systolic and diastolic BP of -4.26 mm Hg (95% CI=-6.06, -2.23) and -2.33 mm Hg (95% CI=-3.70, -0.97), respectively, in TM groups compared with control groups.
  43. A 2015 SR of Zhen Wu Decoction (ZWD) including 7 trials: This systematic review revealed no definite conclusion about the application of ZWD for hypertension due to the poor methodological quality, high risk of bias, and inadequate reporting on clinical data.
  44. A 2015 SR of acupuncture including 23 RCTs: Our review provided evidence of acupuncture as an adjunctive therapy to medication for treating hypertension, while the evidence for acupuncture alone lowing BP is insufficient.
  45. A 2015 SR of xuefu zhuyu decoction (XZD) including 15 studies: This meta-analysis provides evidence that XZD is beneficial for hypertension.
  46. A 2015 SR of Shenqi pill including 4 RCTs: This systematic review firstly provided no definite evidence for the efficacy and safety of Shenqi pill for hypertension based on the insufficient data.
  47. A 2015 SR of Jian Ling Decoction (JLD) including 10 trials: Owing to insufficient clinical data, it is difficult to draw a definite conclusion regarding the effectiveness and safety of JLD for essential hypertension.
  48. A 2015 SR of Chinese herbal medicines (CHM) including 5 trials: No definite conclusions about the effectiveness and safety of CHM for resistant hypertension could be drawn.
  49. A 2015 SR of Chinese medicines (CM) including 27 RCTs: When combined with Western medines, CM as a complementary treatment approach has certain effects for the control of hypertension and protection of target organs.
  50. A 2015 SR of berberine including 17 RCTs: This study indicates that berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect.
  51. A 2015 SR of garlic including 9 double-blind trials: Although evidence from this review suggests that garlic preparations may lower BP in hypertensive individuals, the evidence is not strong.
  52. A 2015 SR of chlorogenic acids (CGAs) including 5 studies: CGA intake causes statistically significant reductions in systolic and diastolic blood pressures.
  53. A 2014 SR of omega-3 fatty acid supplementation including 70 RCTs:  provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure.
  54. A 2014 SR of green tea including 20 RCTs: Green tea intake results in significant reductions in systolic blood pressure
  55. A 2014 SR of probiotics including 9 studies: consuming probiotics may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥10(11) colony-forming units.
  56. A 2014 SR of yoga including 17 trials: The evidence for the effectiveness of yoga as a treatment of hypertension is encouraging but inconclusive.
  57. A 2014 SR of yoga including 7 RCTs: very low-quality evidence was found for effects of yoga on systolic and diastolic blood pressure.
  58. A 2014 SR of yoga including 120 studies: yoga is an effective adjunct therapy for HPT and worthy of inclusion in clinical guidelines.
  59. A 2014 SR of moxibustion:  a beneficial effect of using moxibustion interventions on KI 1 to lower blood pressure compared to antihypertensive drugs.
  60. A 2014 SR of acupuncture including 4 sham-controlled RCTs: acupuncture significantly lowers blood pressure in patients taking antihypertensive medications.
  61. A 2014 SR of Tuina including 7 RCTs: The findings from our review suggest that Tuina might be a beneficial adjuvant for patients with EH
  62. A 2014 SR of ‘kidney tonifying’ (KT) Chinese herbal mixture including 6 studies: Compared with antihypertensive drugs alone, KT formula combined with antihypertensive drugs may provide more benefits for patients with SH.
  63. A 2014 SR of Tongxinluo capsule including 25 studies : There is some but weak evidence about the effectiveness of TXL in treating patients with hypertension.
  64. A 2014 SR of moxibustion including 5 RCTs: no confirm conclusion about the effectiveness and safety of moxibustion as adjunctive treatment for essential hypertension could be made
  65. A 2013 SR of Qi Ju Di Huang Wan (QJDHW) including 10 RCTs: QJDHW combined with antihypertensive drugs might be an effective treatment for lowering blood pressure and improving symptoms in patients with essential hypertension.
  66. A 2013 SR of yoga including 17 studies: Yoga can be preliminarily recommended as an effective intervention for reducing blood pressure.
  67. A 2013 SR of Tianma Gouteng Yin (TGY) including 22 RCTs: No confirmed conclusion about the effectiveness and safety of TGY as adjunctive treatment for essential hypertension … could be made.
  68. A 2013 SR of Zhen Gan Xi Feng Decoction (ZGXFD) including 6 RCTs: ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH
  69. A 2013 SR of Tianmagouteng decoction including 9 RCTs: Tianmagouteng decoction can decrease both systolic and diastolic blood pressure.
  70. A 2013 SR of fish oil including 17 RCTs: The small but statistically significant effects of fish-oil supplements in hypertensive participants in this review have important implications for population health and lowering the risk of stroke and ischaemic heart disease.
  71. A 2013 SR of acupuncture including 35 RCTs: While there are some evidences that suggest potential effectiveness of acupuncture for hypertension, the results were limited by the methodological flaws of the studies.
  72. A 2013 SR of yoga including 6 studies: There is some encouraging evidence of yoga for lowering SBP and DBP.
  73. A 2012 SR of spinal manipulation therapy (SMT) including 10 studies: There is currently a lack of low bias evidence to support the use of SMT as a therapy for the treatment of
  74. A 2012 SR of vitamin C including 29 trials: In short-term trials, vitamin C supplementation reduced SBP and DBP.
  75. A 2012 SR of magnesium supplementation including 22 trials: magnesium supplementation appears to achieve a small but clinically significant reduction in BP, an effect worthy of future prospective large randomised trials using solid methodology.
  76. A 2012 SR of Banxia Baizhu Tianma Decoction (BBTD) including 16 RCTs: There is encouraging evidence of BBTD for lowering SBP, but evidence remains weak.
  77. A 2012 SR of Liu Wei Di Huang Wan (LWDHW) including 6 RCTs: LWDHW combined with antihypertensive drugs appears to be effective in improving blood pressure and symptoms in patients with essential hypertension.
  78. A 2012 SR of aromatherapy including 5 studies: The existing trial evidence does not show convincingly that aromatherapy is effective for hypertension.
  79. A 2012 empty Cochrane review: As no trials could be identified, no conclusions can be made about the role of TGYF in the treatment of primary hypertension.
  80. A 2012 SR of yoga including 10 studies: Not only does yoga reduce high BP but it has also been demonstrated to effectively reduce blood glucose level, cholesterol level, and body weight, major problems affecting the American society.
  81. A 2011 SR of L-arginine including 11 RCTs: This meta-analysis provides further evidence that oral L-arginine supplementation significantly lowers both systolic and diastolic BP.
  82. A 2011 SR of soy isoflavones including 14 RCTs: Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans, and no dose-response relationship was observed.
  83. A 2010 SR of moxibustion including 4 RCTs: There is insufficient evidence to suggest that moxibustion is an effective treatment for hypertension.
  84. A 2010 SR of acupunctures including 20 studies: Because of the paucity of rigorous trials and the mixed results, these findings result in limited conclusions. More rigorously designed and powered studies are needed.
  85. A 2010 SR of cupping including 3 trials: the evidence is not significantly convincing to suggest cupping is effective for treating hypertension.
  86. A 2010 empty Cochrane review: There is insufficient evidence to support the benefit of Roselle for either controlling or lowering blood pressure in patients with hypertension.
  87. A 2009 SR of acupuncture including 11 RCTs: the notion that acupuncture may lower high BP is inconclusive.
  88. A 2008 SR of transcendental meditation including 9 studies: The regular practice of Transcendental Meditation may have the potential to reduce systolic and diastolic blood pressure by approximately 4.7 and 3.2 mm Hg, respectively.
  89. A 2008 SR of relaxation therapies including 25 trials:  the evidence in favour of a causal association between relaxation and blood pressure reduction is weak.
  90. A 2007 SR of qigong including 12 RCTs: There is some encouraging evidence of qigong for lowering SBP, but the conclusiveness of these findings is limited.
  91. A 2007 SR of co-enzyme Q10 including 12 trials: coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects.
  92. A 2007 SR of stress reduction programs including 106 studies: Available evidence indicates that among stress reduction approaches, the Transcendental Meditation program is associated with significant reductions in BP.
  93. A 2006 Cochrance review of magnesium supplementation including 12 RCTs:  the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias.
  94. A 2006 Cochrane review of calcium supplementation including 13 RCTs: evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias.

ALMOST 100 NEW SRs!

To be honest, if I had known the volume of the material, I would probably not have tackled this task. Since the publication of my mini-review in 2005, there has been an explosion of similar papers:

  • 1 in 2005
  • 2 in 2006
  • 3 in 2007
  • 2 in 2008
  • 1 in 2009
  • 4 in 2010
  • 2 in 2011
  • 8 in 2012
  • 8 in 2013
  • 12 in 2014
  • 12 in 2015
  • 6 in 2016
  • 9 in 2017
  • 7 in 2018
  • 12 in 2019

As this is based on very simple Medline searches, the list is certainly not complete. Despite this fact, several conclusions seem to emerge:

  1. There is no shortage of SCAMs that have been tested for hypertension.
  2. Most seem to have positive effects; in many cases, they seem too good to be true.
  3. Many of the SRs are of poor methodological quality, based on poor quality primary studies, published in less than reputable journals. Some SRs, for instance, include studies without a control group which is likely to lead to false-positive overall conclusions about the effectiveness of the SCAM in question.
  4. In recent years, there are more and more SRs by Chinese authors focussed on Chinese herbal mixtures that are unknown and unobtainable outside China. These SRs are invariably based on studies published in Chinese language in journals that are inaccessible. This means it is almost impossible for the reader, reviewer or editor to check their accuracy. The reliability of the conclusions of these SRs must therefore be doubted.
  5. Most of the primary studies included in the SRs lack long-term data. Thus the usefulness of the SCAM in question is questionable.
  6. With several of the SCAMs, the dose of the treatment and treatment schedule is less than clear. For instance, one might ask how frequently a patient should have acupuncture to control her hypertension.
  7. Some of the SCAMs assessed in these SRs seem of doubtful practicality. For instance, it might not be feasible nor economical for patients to receive regular acupuncture to manage their blood pressure.
  8. Several contradictions emerge from some of the SRs of the same modality. This is particularly confusing because SRs are supposed to be the most reliable type of evidence. In most instances, however, the explanation can easily be found by looking at the quality of the SRs. If SRs are based on uncontrolled studies, or if they fail to critically evaluate the reliability of the included primary trials, they are likely to arrive at conclusions that are too positive. Examples for such confusion are the multiple SRs of co-enzyme Q10 or the three yoga SRs of 2014.
  9. Because of this confusion, SCAM advocates are able to select false-positive SRs to support their opinion that SCAM is effective.
  10. Despite a substantial amount of positive evidence, none of the SCAMs have become part of the routine in the management of hypertension. A 2013 statement by the American Heart Association entitled Beyond medications and diet: alternative approaches to lowering blood pressure: a scientific statement from the american heart association concluded that it is reasonable for all individuals with blood pressure levels >120/80 mm Hg to consider trials of alternative approaches as adjuvant methods to help lower blood pressure when clinically appropriate. A suggested management algorithm is provided, along with recommendations for prioritizing the use of the individual approaches in clinical practice based on their level of evidence for blood pressure lowering, risk-to-benefit ratio, potential ancillary health benefits, and practicality in a real-world setting. 

What lessons might this brief overview of SRs teach us? I think the following points are worth considering:

  • Systematic reviews are the best type of evidence we have for estimating the effectiveness of treatments. But it is essential that they include a strong element of CRITICAL evaluation of the primary studies. Without it, a SR is incomplete and potentially counter-productive.
  • The primary studies of SCAM are far too often of poor quality. This means that researchers should thrive to improve the rigour of their investigations.
  • Both poor-quality primary studies and uncritically conducted SRs are prone to yielding findings that are too good to be true.
  • Editors and reviewers have a responsibility to prevent the publication of trials and SRs that are of poor quality and thus likely to mislead us.
  • Those SCAMs that have shown promising effects on hypertension (for instance Tai chi) should now be submitted to further independent scrutiny to find out whether their efficacy and usefulness can be confirmed, for instance, by 24-h ambulatory and daily home blood pressure monitoring and studies testing their acceptability in real life settings. Subsequently, we ought to determine whether the SCAM in question can be reasonably integrated in routine blood pressure management.
  • The adjunctive use of a SCAM that has been proven to be effective and practical seems a reasonable approach. Yet, it requires proper scientific scrutiny.
  • There is a paucity of cost-effectiveness studies and investigations of the risks of SCAM which needs to be addressed before any SCAM is considered for routine care.

Many homeopaths will tell you that they like to treat children because they respond particularly well to their remedies. This notion is widely promoted and often is the reason why mothers take their kid to homeopath. Some parents even take it for established wisdom. Yet there is a major problem with it:

IT IS NOT TRUE!

A systematic review and meta-analysis investigated the benefits and risks for oral homeopathic remedies used to treat and prevent acute respiratory tract infections (ARTIs) in children. Extensive literature searches were used to identify all double-blinded randomized trials in children, treated with oral homeopathic remedies versus placebo or conventional treatments for ARTI. Studies were reviewed in duplicate for inclusion, data extraction and risk of bias. Meta-analysis was performed on only 4 outcomes. Other outcomes were reported narratively.

Eight studies (1562 children) were included. Four studies examined treatment and 4 prevention of ARTIs. Four studies involved homeopaths individualizing treatment versus four with non-individualized treatments. Three studies had high risk of bias in at least one domain. All studies with low risk of bias showed no benefit from homeopathy; trials at uncertain and high risk of bias reported beneficial effects. Two individualized treatment studies (N=155) did not show benefit on short-term or long-term cure. Prevention trials showed no significant outcomes: recurrence of ARTIs. No serious adverse events were reported.

The authors concluded that the effectiveness for homeopathic remedies for childhood ARTIs is not supported in higher quality trials.

This paper is the up-date of the current Cochrane review which concluded that pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on recurrence of ARTI or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn.

And to prevent errors about conditions other than ARTIs, let me remind you of our systematic review of homeopathy for ANY childhood disease. It concluded that the evidence from rigorous clinical trials of any type of therapeutic or preventive intervention testing homeopathy for childhood and adolescence ailments is not convincing enough for recommendations in any condition.

So, next time you hear a homeopath claim that his/her treatments are especially good for kids, be warned: the claim merely supports his/her income but not your child.

 

Together with a co-worker, Prof Walach conducted a systematic review of mistletoe extracts (Rudolf Steiner’s anti-cancer drug) as a treatment for improving the quality of life (QoL) of cancer patients. They included all prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions.

Walach included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41-0.81, p < 0,00001). The effect was stronger for younger patients, with longer treatment, in studies with lower risk of bias, in randomized and blinded studies. Sensitivity analyses supported the validity of the finding. 50% of the QoL subdomains (e.g. pain, nausea) showed a significant improvement after mistletoe treatment. Most studies had a high risk of bias or at least raise some concern.

The authors concluded that mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome.

This is a surprising conclusion, not least because – as reported on this blog – only a year ago another German team of researchers conducted a similar review and came to a very different conclusion. Here is their abstract again:

Purpose: One important goal of any cancer therapy is to improve or maintain quality of life. In this context, mistletoe treatment is discussed to be highly controversial. The aim of this systematic review is to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments.

Methods: In September and October 2017, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and “Science Citation Index Expanded” (Web of Science) were systematically searched.

Results: The search strategy identified 3647 articles and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Regarding quality of life, 17 publications reported results. Studies with better methodological quality show less or no effects on quality of life.

Conclusions: With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

How can this discrepancy be explained? Which of the reviews is drawing the correct conclusion? Here are some relevant details that could help finding an answer to these questions:

  • Walach is a psychologist by training, while the senior author of the 2019 review, Jutta Huebner, is an oncologist.
  • Huebner included only randomised clinical trials (RCTs), whereas Walach included any interventional and non-interventional prospective controlled study.
  • Huebner included 17 RCTs that reported QoL data, while Walach included 26 publications with 30 data sets including 5 non-randomised studies.
  • Several of the primary studies had been published multiple times at different stages of completion. Walach included these as independent data sets, while Huebner included each study only once.
  • Huebner looked at QoL, whereas Walach also considered measurements of self-regulation as outcome measures.
  • Both reviews point out that the methodological quality of the primary studies was often poor; Walach drew a positive conclusion regardless, while Huebner did not and pointed out that studies with better methodology show less or no effects on quality of life or side effects of cancer therapy.
  • Walach’s review was funded by funded by the Förderverein komplementärmedizinische Forschung, Arlesheim, Switzerland, a lobby group for mistletoe therapy, while Huebner’s work was funded by the German Guideline “S3 Leitlinie Komplementärmedizin in der Behandlung von onkologischen PatientInnen (Registernummer 032-055OL)” funded by the German Cancer Aid (Fördernummer 11583) within the German Guideline Program in Oncology and by the working group Prevention and Integrative Oncology of the German Cancer Society.

I am sure there are other important differences, but the ones listed above suffice, I think, to decide which of the two papers is trustworthy and which is not.

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