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

clinical trial

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Shiatsu is a (mostly) manual therapy that was popularised by Japanese Tokujiro Namikoshi (1905–2000). It developed out of the Chinese massage therapy, ‘tui na’. The word shiatsu means finger pressure in Japanese; however, a range of devices is also being promoted for shiatsu. The evidence that shiatsu is effective for any condition is close to non-existent.

This study aimed to investigate the effect of Shiatsu massage on agitation in mechanically ventilated patients.

A total of 68 mechanically ventilated patients were randomly assigned to two groups. Patients in the intervention group received three 5-minute periods of Shiatsu massage with a 2-minute break between them, while patients in the control group only received a touch on the area considered for the message. Data were collected before and after the intervention using the Richmond Agitation-Sedation Scale (RASS) and then analyzed.

The results showed that the level of agitation significantly decreased in the intervention group compared to the control group (p=.001).

The authors concluded that the application of shiatsu massage seems to be effective in managing agitation in mechanically ventilated patients. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.

It is good to see that, as far as I know for the first time, an attempt was made to control for placebo and other non-specific effects in a trial of shiatsu. However, in itself, the attempt is not convincing. What we need to know is whether the attempt was successful or not. Were the patients fully blinded and unable to tell the difference between verum and sham? From reading not just the abstract but the full paper, I do not get the impression that patients were successfully blinded. This means that the results might be entirely due to the effect of deblinding.

 

As you know, I am not in the habit of telling personal stories on this blog. Today, allow me to make an exception by taking you back 40 years into my own history.

Back in the 1980s, I spent much of my time doing research in hemorheology (flow properties of blood). At the time, this was a buoyant area of research, and my late friend Arpad Matrai and I were enthusiastically investigating it, first in London under John Dormandy and later at the LMU in Munich. But we were by no means the only team working in hemorheology. Another group at Aachen was much larger, better-funded, and in many ways way ahead of us. One member of that group regularly irritated us; this was Holger Kiesewetter, the ‘hero’ of my story.

Arpad was sure that much of Kiesewetter’s work and even more of his financial dealings were suspect (“How come a junior research can afford driving a Porsche?”, he used to wonder). Something did not seem quite right. Despite our reservations, we did collaborate occasionally. In 1984, we even managed to co-organize a conference and jointly publish its proceedings.

After my friend and co-worker Arpad had died of leukemia, I gradually drifted back into clinical medicine, became a professor of rehab medicine first in Hannover and then in Vienna. This also meant that I completely lost touch with Holger Kiesewetter. I was, therefore, more than a little surprised to one day receive a phone call from him in Vienna. He told me that he had applied for a professorship at my Uni and asked me to support his application. I did not promise to do so and I certainly did not lend my support to his application. Quite simply, I remembered too many instances that gave me reasons to be concerned about my ‘friend’s’ integrity.

Kiesewetter did not get the Vienna post but I later learned that he had become a professor of transfusion medicine at the Charite in Berlin. In the mid-1990s, a chance meeting at an airport occurred when we were both catching flights. He told me that he was doing fine, and he seemed to have his fingers in many pies.

Then I lost sight of him completely.

Until yesterday, that is.

I was doing some searches on herbal remedies when I came across the intriguing subject of ‘BIO VIAGRA‘. A German article reported this:

“In clinical trials, 50 men had much better sex afterward, more fun in bed, and just generally felt better about themselves,” the Sueddeutsche Zeitung daily cited Olaf Schroeder from Berlin’s Charite hospital as saying. “Their libido was even higher than the control group taking Viagra,” he said. The potent cocktail includes tribulus terrestris, a herb already used in alternative medicine, a root vegetable found in the Andes called maca and grape juice extract, newspapers said. The treatment, dubbed “Plantagrar”, is due to be launched in early 2010, the Bild daily said.

Having published a review of maca, I was interested and continued searching.

Another article stated that a certain Mr. Schröder had stated that he had investigated the efficacy of the remedy on 50 test persons. However, the data of the experiment have not been published. In addition, the researchers’ procedure has been massively criticized: 25 men were given the bio-potency drug, 25 others a placebo, i.e. a tablet without active ingredients. Afterward, the test persons were to compare their experiences with those they had had with Viagra. Fritz Sörgel, director of the Nuremberg Institute for Biomedical and Pharmaceutical Research, calls the procedure “completely dubious”. “This is a completely new kind of study that this doctoral student has invented.” The number of test persons is much too low, the comparison with Viagra cannot be taken seriously.

This sounded already quite dodgy, and a third article in the usually reliable German Medical Journal provided more details:

For several months, those involved kept a low profile, but now the affair surrounding the development of a herbal aphrodisiac at Berlin’s Charité University Hospital has consequences: Last week, the head of the Institute for Transfusion Medicine, Prof. Dr.-Ing. Dr. med. Holger Kiesewetter, was given leave of absence. This step was taken “at his own request”, said hospital spokesperson Claudia Peter. The withdrawal came about two weeks after the public prosecutor’s office searched his work and private rooms as well as other locations.

The “Bio-Viagra affair” had caused a furore in mid-March. A doctoral student of Kiesewetter’s had claimed to the Deutsche Presse-Agentur that he had successfully developed an aphrodisiac on a purely herbal basis. Some daily newspapers reported on the remedy, which was called “Plantagrar”. A little later, however, the Charité management denied it. It was “the activity of an employee (. . .) on his own responsibility”. The case also came to the attention of the drug supervisory authority. Erectile dysfunctions are recognised diseases according to the ICD-10 classification system. The “Bio-Viagra” was therefore a drug whose development should have been controlled, the state office for health and social affairs said.

A spokesperson for the Berlin public prosecutor’s office confirmed the presumption of a violation of the German Medicines Act to the Deutsches Ärzteblatt. In addition, Kiesewetter is being investigated for bribery, corruption and breach of trust to the detriment of the Charité. The head of the institute had apparently been promised benefits by private companies.

That sounded very much like the Kiesewetter I remembered. I was unable to find the actual trial or more details about the herbal remedy. The scandal seems to have put an end not only to the university career of the researchers but also to the aphrodisiac.

However, I did find a Wiki page about Kiesewetter that suggests that ‘bio viagra’ was by no means the only escapade from the straight and narrow. But what is he up to today? Did he retire? No, after the debacle at the Charite, he seems to have gone into private practice:

After working as director of the Institute for Transfusion Medicine and Immunohaematology at the Charité and head of the coagulation outpatient clinic at the Charité, he has been providing patient care at the Hämostaseologicum Berlin-Mitte since 2010.

This is also the address he used for his most recent (2020) publication.

Am I worried about my old ‘friend’?

No, I am confident that he is doing just fine … financially, I mean.

 

Cupping is a so-called alternative medicine (SCAM) that has been around for millennia in many cultures. We have discussed it repeatedly on this blog (see, for instance, here, here, and here). This new study tested the effects of dry cupping on pain intensity, physical function, functional mobility, trunk range of motion, perceived overall effect, quality of life, psychological symptoms, and medication use in individuals with chronic non-specific low back pain.

Ninety participants with chronic non-specific low back pain were randomized. The experimental group (n = 45) received dry cupping therapy, with cups bilaterally positioned parallel to the L1 to L5 vertebrae. The control group (n = 45) received sham cupping therapy. The interventions were applied once a week for 8 weeks.

Participants were assessed before and after the first treatment session, and after 4 and 8 weeks of intervention. The primary outcome was pain intensity, measured with the numerical pain scale at rest, during fast walking, and during trunk flexion. Secondary outcomes were physical function, functional mobility, trunk range of motion, perceived overall effect, quality of life, psychological symptoms, and medication use.

On a 0-to-10 scale, the between-group difference in pain severity at rest was negligible: MD 0.0 (95% CI -0.9 to 1.0) immediately after the first treatment, 0.4 (95% CI -0.5 to 1.5) at 4 weeks and 0.6 (95% CI -0.4 to 1.6) at 8 weeks. Similar negligible effects were observed on pain severity during fast walking or trunk flexion. Negligible effects were also found on physical function, functional mobility, and perceived overall effect, where mean estimates and their confidence intervals all excluded worthwhile effects. No worthwhile benefits could be confirmed for any of the remaining secondary outcomes.

The authors concluded that dry cupping therapy was not superior to sham cupping for improving pain, physical function, mobility, quality of life, psychological symptoms or medication use in people with non-specific chronic low back pain.

These results will not surprise many of us; they certainly don’t baffle me. What I found interesting in this paper was the concept of sham cupping therapy. How did they do it? Here is their explanation:

For the experimental group, a manual suction pump and four acrylic cups size one (internal diameter = 4.5 cm) were used for the interventions. The cups were applied to the lower back, parallel to L1 to L5 vertebrae, with a 3-cm distance between them, bilaterally. The dry cupping application consisted of a negative pressure of 300 millibars (two suctions in the manual suction pump) sustained for 10 minutes once a week for 8 weeks.

In the control group, the exact same procedures were used except that the cups were prepared with small holes < 2 mm in diameter to release the negative pressure in approximately 3 seconds. Double-sided adhesive tape was applied to the border of the cups in order to keep them in contact with the participants’ skin.

So, sham-controlled trials of cupping are doable. Future trialists might now consider the inclusion of testing the success of patient-blinding when conducting trials of cupping therapy.

Bloodletting therapy (BLT) has been widely used for centuries until it was discovered that it is not merely useless for almost all diseases but also potentially harmful. Yet in so-called alternative medicine (SCAM) BLT is still sometimes employed, for instance, to relieve acute gouty arthritis (AGA). This systematic review aimed to evaluate the feasibility and safety of BLT in treating AGA.

Seven databases were searched from the date of establishment to July 31, 2020, irrespective of the publication source and language. BLT included fire needle, syringe, three-edged needle, and bloodletting followed by cupping. The included articles were evaluated for bias risk by using the Cochrane risk of bias assessment tool.

Twelve studies involving 894 participants were included in the final analysis. A meta-analysis suggested that BLT was highly effective in relieving pain (MD = -1.13, 95% CI [-1.60, -0.66], P < 0.00001), with marked alterations in the total effective (RR = 1.09, 95% [1.05, 1.14], P < 0.0001) and curative rates (RR = 1.37, 95%CI [1.17, 1.59], P < 0.0001). In addition, BLT could dramatically reduce serum C-reactive protein (CRP) level (MD = -3.64, 95%CI [-6.72, -0.55], P = 0.02). Both BLT and Western medicine (WM) produced comparable decreases in uric acid (MD = -18.72, 95%CI [-38.24, 0.81], P = 0.06) and erythrocyte sedimentation rate (ESR) levels (MD = -3.01, 95%CI [-6.89, 0.86], P = 0.13). Lastly, we demonstrated that BLT was safer than WM in treating AGA (RR = 0.36, 95%CI [0.13, 0.97], P = 0.04).

The authors concluded that BLT is effective in alleviating pain and decreasing CRP level in AGA patients with a lower risk of evoking adverse reactions.

This conclusion is optimistic, to say the least. There are several reasons for this statement:

  • All the primary studies came from China (and we have often discussed that such trials need to be taken with a pinch of salt).
  • All the studies had major methodological flaws.
  • There was considerable heterogeneity between the studies.
  • The treatments employed were very different from study to study.
  • Half of all studies failed to mention adverse effects and thus violate medical ethics.

Osteopathic manipulative treatment (OMT) is advocated not merely for spinal or musculoskeletal problems, as many consumers seem to think, osteopaths also claim it to be effective for (almost) every condition. Some osteopaths who believe in the gospel of Andrew Still, the founder of osteopathy, recommend it even to facilitate breastfeeding.

But is it effective? 

A double-blind randomised controlled trial to answer this question was conducted between July 2013 and March 2016. Breastfed term infants were eligible if one of the following criteria was met: suboptimal breastfeeding behaviour, maternal cracked nipples or maternal pain. The infants were randomly assigned to the intervention or the control group. The intervention consisted of two sessions of early OMT, while in the control group, the manipulations were performed on a doll behind a screen. The primary outcome was the exclusive breastfeeding rate at 1 month, which was assessed in an intention-to-treat analysis. Randomisation was computer generated and only accessible to the osteopath practitioner. The parents, research assistants and paediatricians were masked to group assignment.

One hundred twenty-eight mother-infant dyads were randomised, with 64 assigned to each group. In each group, five infants were lost to follow-up. In the intervention group, 31 of 59 (53%) of infants were still exclusively breastfed at 1 month vs 39 of 59 (66%) in the control group, (OR 0.55, 95% CI 0.26 to 1.17; p=0.12). After adjustment for suboptimal breastfeeding behaviour, caesarean section, use of supplements and breast shields, the adjusted OR was 0.44 (95% CI 0.17 to 1.11; p=0.08). No adverse effects were reported in either group.

The authors concluded succinctly that OMT did not improve exclusive breastfeeding at 1 month.

Surprised?

Suppose not!

The only question that I can think of is this: why did osteopaths ever think that OMT might facilitate breastfeeding?

This study assessed the effectiveness of Oscillococcinum in the protection from upper respiratory tract infections (URTIs) in patients with COPD who had been vaccinated against influenza infection over the 2018-2019 winter season.

A total of 106 patients were randomized into two groups:

  • group V received influenza vaccination only
  • group OV received influenza vaccination plus Oscillococcinum® (one oral dose per week from inclusion in the study until the end of follow-up, with a maximum of 6 months follow-up over the winter season).

The primary endpoint was the incidence rate of URTIs (number of URTIs/1000 patient-treatment exposure days) during follow-up compared between the two groups.

There was no significant difference in any of the demographic characteristics, baseline COPD, or clinical data between the two treatment groups (OV and V). The URTI incidence rate was significantly higher in group V than in group OV (2.9 versus 1.2 episodes/1000 treatment days, difference OV-V = -1.7; p=0.0312). There was a significant delay in occurrence of an URTI episode in the OV group versus the V group (mean ± standard error: 48.7 ± 3.0 versus 67.0 ± 2.8 days, respectively; p=0.0158). Limitations to this study include its small population size and the self-recording by patients of the number and duration of URTIs and exacerbations.

The authors concluded that the use of Oscillococcinum in patients with COPD led to a significant decrease in incidence and a delay in the appearance of URTI symptoms during the influenza-exposure period. The results of this study confirm the impact of this homeopathic medication on URTIs in patients with COPD.

Primary endpoint, comparison of the number of upper respiratory tract infections in the two treatment groups during follow-up

This prospective, randomized, single-center study was funded by Laboratoires Boiron, was conducted in the Pneumology Department of Charles Nicolle Hospital, Tunis, and was written up by a commercial firm specializing in writing for the pharmaceutical industry. The latter point may explain why it reads well and elegantly glosses over the many flaws of the trial.

If I did not know better, I might suspect that the study was designed to deceive us (Boiron would, of course, never do this!): The primary endpoint was the incidence rate of URTIs (number of URTIs/1000 patient-treatment exposure days) in the two groups during the follow-up period. This rate is calculated as the number of episodes of URTIs per 1000 days of follow-up/treatment exposure. The rates were then compared between the OV and V groups. The following symptoms were considered indicative of an URTI: fever, shivering, runny or blocked nose, sneezing, muscular aches/pain, sore throat, watery eyes, headaches, nausea/vomiting, diarrhoea, fatigue and loss of appetite.

This means that there was no verification whatsoever of the primary endpoint. In itself, this flaw would perhaps not be so bad. But put it together with the fact that patients were not blinded (there were no placebos!), it certainly is fatal.

In essence, the study shows that patients who perceive to receive treatment will also perceive to have fewer URTIs.

SURPRISE, SURPRISE! 

Lian gong (LG), also called Lian Gong Shi Ba Fa, is a form of so-called alternative medicine (SCAM) from China.  More specifically, it is a set of stretching, breathing exercises, and self-massaging techniques aimed at preventing and relieving stress as well as acute pains around the neck, shoulders, back, hips, legs, joints, and connective tissues.  Even though it is relatively new, it is based on old Chinese stretching, breathing, and warm-up exercises dating back more than 1,000 years, including the Eight Silk Brocade (八段錦).  Lian gong has spread rapidly from China to other countries, especially to Japan and Brazil.

Lian Gong was developed by Dr. Zhuang Yuan Ming (1919- ), a traditional Chinese medical doctor, who started conducting a series of clinical trials around 1974 in a Shanghai hospital on patients suffering from a variety of stress-related conditions. Lian Gong is now being promoted as “massage in motion”.

One of the few controlled clinical studies of Liam gong aimed to evaluate the effects of LG on the impact of dizziness on the quality of life and fear of falling in primary health care patients. It was designed as a randomized clinical trial with 36 patients with dizziness not caused by central changes. The participants were randomly assigned to 3 groups:

  • the Liam gong (LG) group ( n = 11),
  • the vestibular rehabilitation (VR) group ( n = 11),
  • the control group ( n = 14).

The treatments were carried out over a period of 12 weeks.

Lian gong reduced the influence of dizziness on the quality of life in physical (1.8 points, 95% confidence interval [CI]: 0.2-3.4), functional (4.0 points, 95% CI: 2.1-5.9), and emotional domains of quality of life (4.4 points, 95% CI: 1.7-7.2), with no differences, compared with VR.

The authors concluded that Lian gong was shown to be an effective balance rehabilitation strategy to reduce the impact of dizziness on quality of life, with similar results to those of VR.

Unfortunately, this study has many flaws – not least its minute sample size. Therefore, the conclusions seem more than a little over-optimistic. I would not be all that surprised to learn that these exercises can have beneficial effects for a range of conditions. What seems doubtful in my view, however, is whether it is superior to more conventional exercise therapies.

Ovariohysterectomy (OH) is one of the most frequent elective surgical procedures in routine veterinary practice. The aim of this study was to evaluate analgesia with Arnica montana 30cH during the postoperative period after elective OH.

Thirty healthy female dogs, aged 1 to 3 years, weighing 7 to 14 kg, were selected at the Veterinary Hospital in Campo Mourão, Paraná, Brazil. The dogs underwent the surgical procedure with an anaesthetic protocol and analgesia that had the aim of maintaining the patient’s wellbeing. After the procedure, they were randomly divided into three groups of 10. One group received Arnica montana 30cH; another received 5% hydroalcoholic solution; and the third group, 0.9% NaCl saline solution. All animals received four drops of the respective solution sublingually and under blinded conditions, every 10 minutes for 1 hour, after the inhalational anaesthetic had been withdrawn. The Glasgow Composite Measure Pain Scale was used to analyse the effect of therapy. Analysis of variance (ANOVA) followed by the Tukey test was used to evaluate the test data. Statistical differences were deemed significant when p ≤0.05.

The results show that the Arnica montana 30cH group maintained analgesia on average for 17.8 ± 3.6 hours, whilst the hydroalcoholic solution group did so for 5.1 ± 1.2 hours and the saline solution group for 4.1 ± 0.9 hours (p ≤0.05).

The authors concluded that these data demonstrate that Arnica montana 30cH presented a more significant analgesic effect than the control groups, thus indicating its potential for postoperative analgesia in dogs undergoing OH.

I do not have access to the full article (I was fired by the late Peter Fisher from the editorial board of the journal ‘HOMEOPATHY’) which puts me in a somewhat difficult position:

  • not reporting this study could be construed as an anti-homeopathy bias,
  • and reporting it handicaps me as I cannot assess essential details.

So, if anyone has access, please send the full paper to me and I will then study it and revise this post accordingly.

Judging from the abstract, I have to say that the results seem far too good to be true. I doubt that any oral remedy can have the effect that is being described here – let alone one that has been diluted (sorry, potentised) at a rate of 1: 1000000000000000000000000000000000000000000000000000000000000. That fact alone reduces the plausibility of the finding to zero.

At this stage, I do wonder who peer-reviewed the study and ask myself whether the rough data have been checked for reliability.

Psychosocial distress, depression, or anxiety are frequent problems of women after a breast cancer diagnosis and treatment. Many try so-called alternative medicine (SCAM) in an attempt to deal with them. But is this effective?

The purpose of this study was to assess the potential benefit of lavender oil as a perioperative adjunct to improve anxiety, depression, pain, and sleep in women undergoing microvascular breast reconstruction.

This was a prospective, single-blinded, randomized, controlled trial of 49 patients undergoing microvascular breast reconstruction. Patients were randomized to receive lavender oil or a placebo (coconut oil) throughout their period of hospitalization. The effect of lavender oil on perioperative stress, anxiety, depression, sleep, and pain was measured using the hospital anxiety and depression scale, Richards-Campbell Sleep Questionnaire, and the visual analogue scale.

Twenty-seven patients were assigned to the lavender group and 22 patients were assigned to the control group. No significant differences were seen in the perioperative setting between the groups with regard to anxiety (p = 0.82), depression, sleep, or pain scores. No adverse events were noted, and no significant differences in surgery-related complications were observed. When evaluating the entire cohort, postoperative anxiety scores were significantly lower than preoperative scores, while depression scores were significantly higher postoperatively as compared with preoperatively.

The authors concluded that, in the setting of microvascular breast reconstruction, lavender oil and aromatherapy had no significant adverse events or complications; however, there were no measurable advantages pertaining to metrics of depression, anxiety, sleep, or pain as compared with the control group.

One could argue that the sample size of the trial was too low to pick up small differences in the outcome measures. Yet, even then, the findings do not suggest that the treatment did make a large enough difference to justify the effort and expense of the treatment.

One could also argue that – who cares? – if a patient wants aromatherapy (or another SCAM that is harmless), why not? The answer to this is the fact that researchers have the ethical duty to identify the most effective treatment, and clinicians have the ethical duty to employ not just any odd therapy but the one that works demonstrably best. Seen from this perspective, the place of SCAM in cancer care seems far less certain than many enthusiasts try to make us believe.

Neck pain affects a vast number of people and leads to reduced quality of life and high costs. Clinically, it is a difficult condition to manage, and the effect sizes of the currently available treatments are moderate at best. Activity and manual therapy are first-line treatment options in several guidelines. But how effective are they really?

This study investigated the combination of home stretching exercises and spinal manipulative therapy in a multicentre randomized controlled clinical trial, carried out in a multidiscipline range of primary care clinics.

The treatment modalities utilized were spinal manipulative therapy combined with home stretching exercises compared to home stretching exercises alone. Both groups received 4 treatments for 2 weeks. The primary outcome was pain, where the subjective pain experience was investigated by assessing pain intensity (NRS – 11) and the quality of pain (McGill Pain Questionnaire). Neck disability and health status were secondary outcomes, measured using the Neck Disability Indexthe EQ-5D, respectively.

One hundred thirty-one adult subjects were randomized to one of the two treatment groups. All subjects had experienced persistent or recurrent neck pain the previous 6 months and were blinded to the other group intervention. The clinicians provided treatment for subjects in both groups and could not be blinded. The researchers collecting data were blinded to treatment allocation, as was the statistician performing data analyses. An intention-to-treat analysis was used.

Sixty-six subjects were randomized to the intervention group, and 65 to the control group. For NRS – 11, a B-coefficient of – 0,01 was seen, indication a 0,01 improvement for the intervention group in relation to the control group at each time point with a p-value of 0,305. There were no statistically significant differences between groups for any of the outcome measures.

Four intense adverse events were reported in the study, three in the intervention group, and one in the control group. More adverse incidents were reported in the intervention group, with a mean pain intensity (NRS-11) of 2,75 compared to 1,22 in the control group. There were no statistically significant differences between the two groups.

The authors concluded that there is no additional treatment effect from adding spinal manipulative therapy to neck stretching exercises over 2 weeks for patients with persistent or recurrent neck pain.

This is a rigorous and well-reported study. It suggests that adjuvant manipulations are not just ineffective for neck pain, but also cause some adverse effects. This seems to confirm many previously discussed investigations concluding that chiropractors do not generate more good than harm for patients suffering from neck pain.

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