The sale and promotion of a therapeutic drug in most countries require rigorous assessment and licencing by that country’s therapeutic regulatory body. However, a new surgical technique can escape such checks and overview unless the technique is subject to local medical ethics review in the context of a research trial. New medical devices in Australia such as carbon dioxide or Er-YAG lasers can be listed on its therapeutic register without critical review of their efficacy and safety. Thermal injury to the postmenopausal vaginal wall in the hope of rejuvenating it has become a lucrative fad for some surgeons outside formal well-conducted clinical trials.
There are many published studies of this technique but the large majority are small, uncontrolled and observational. The few randomised controlled trials using sham controls show a placebo effect and debatable clinical efficacy with limited follow-up of adverse effects. A review of these therapies in July 2020 published by The National Institute for Health and Care Excellence summarised apparent claims for some efficacy in terms of vaginal dryness, dyspareunia, sexual function, and incontinence but noted confounding in the study’s designs such as concurrent breast cancer treatments, local oestrogen therapy and lubricants (!). Most studies had very limited follow up for adverse events but elsewhere the literature has reported burns, infection, increased dyspareunia and scarring. There is no physiological mechanism by which burning atrophic vaginal epithelium will magically rejuvenate it.
A recent well-conducted randomised sham-controlled trial with a 12-month follow-up of Fractional Carbon Dioxide Laser for the treatment of vaginal symptoms associated with menopause has been published in JAMA by Li et al has shown no efficacy for this treatment(2).
At 12 months, there was no difference in overall symptom severity based on a 0-100 scale (zero equals no symptoms), with a reduction in symptom severity of 17.2 in the treatment group compared with 26.6 in the sham group.
The treatment had no impact on quality of life. “Sexual activity rates and quality of sex were not significantly different between the groups at baseline or 12 months”. The study compared 46 paired vaginal wall biopsies, taken at baseline and six months into treatment, and no significant histological improvement with laser was evident.
“The annual cost of laser treatment to the individual for management of vaginal menopausal symptoms was reported to be AUD$2,733, and because there is no demonstrable difference versus sham treatment, it cannot be considered to be cost-effective.”
Although one could still call for more quality sham-controlled randomised trials in different circumstances there is no justification for touting this therapy commercially. Complications following this therapy outside of ethical trials could become the next medico-legal mine-field.
Vaginal atrophy in the years after menopause is almost universal and is primarily due to oestrogen deficiency. The efficient solution is local vaginal oestrogen or systemic hormone replacement therapy. However, the misreporting of the Women’s Health Initiative and Million Women’s Study has created exaggerated fear of oestrogen therapies and thus a market for alternative and often unproven therapies (3). The way forward is education and tailoring of hormonal therapies to minimise risk and maximise efficacy and quality of life and not to resort to quackery.
2. Li FG, Maheux-Lacroix S, Deans R et al. Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms A Randomized Clinical Trial. JAMA. 2021;326:1381-1389.
3. MacLennan AH. Evidence-based review of therapies at the menopause. Int J Evid Based Healthc 2009; 7: 112-123.
Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. It is increasingly being used as a recreational drug, to help with opium withdrawal, and as a so-called alternative medicine (SCAM) for pain, erectile dysfunction, as a mood stabilizer, and for boosting energy or concentration. When ingested, Kratom leaves produce stimulant and opioid-like effects (see also my previous post).
Kratom contains 7‑hydroxymitragynine, which is active on opioid receptors. The use of kratom carries significant risks, e.g. because there is no standardized form of administration as well as the possibility of direct damage to health and of addiction.
There are only very few clinical trials of Kratom. One small placebo-controlled study concluded that the short-term administration of the herb led to a substantial and statistically significant increase in pain tolerance. And a recent review stated that Kratom may have drug interactions as both a cytochrome P-450 system substrate and inhibitor. Kratom does not appear in normal drug screens and, especially when ingested with other substances of abuse, may not be recognized as an agent of harm. There are numerous cases of death in kratom users, but many involved polypharmaceutical ingestions. There are assessments where people have been unable to stop using kratom therapy and withdrawal signs/symptoms occurred in patients or their newborn babies after kratom cessation. Both banning and failure to ban kratom places people at risk; a middle-ground alternative, placing it behind the pharmacy counter, might be useful.
In Thailand, Kratom had been outlawed since 1943 but now it has become (semi-)legal. Earlier this year, the Thai government removed the herb from the list of Category V narcotics. Following this move, some 12,000 inmates who had been convicted when Kratom was still an illegal drug received amnesty. However, Kratom producers, traders, and even researchers will still require licenses to handle the plant. Similarly, patients looking for kratom-based supplements will need a valid prescription from licensed medical practitioners. Thai law still prohibits bulk possession of Kratom. Users are encouraged to handle only minimum amounts of the herb to avoid getting prosecuted for illegal possession.
In 2018, the US Food and Drug Administration stated that Kratom possesses the properties of an opioid, thus escalating the government’s effort to slow usage of this alternative pain reliever. The FDA also wrote that the number of deaths associated with Kratom use has increased to a total of 44, up from a total of 36 since the FDA’s November 2017 report. In the majority of deaths that the FDA attributes to Kratom, subjects ingested multiple substances with known risks, including alcohol.
In most European countries, Kratom continues to be a controlled drug. In the UK the sale, import, and export of Kratom are prohibited. Yet, judging from a quick look, it does not seem to be all that difficult to obtain Kratom via the Internet.
Static or motion manual palpation tests of the spine are commonly used by chiropractors and osteopaths to assess pain location and reproduction in low back pain (LBP) patients. But how reliable are they?
The purpose of this review was to evaluate the reliability and validity of manual palpation used for the assessment of LBP in adults. The authors systematically searched five databases from 2000 to 2019 and critically appraised the internal validity of studies using QAREL and QUADAS-2 instruments.
A total of 2023 eligible articles were identified, of which 14 were at low risk of bias. Evidence suggests that reliability of soft tissue structures palpation is inconsistent, and reliability of bony structures and joint mobility palpation is poor. Preliminary evidence was found to suggest that gluteal muscle palpation for tenderness may be valid in differentiating LBP patients with and without radiculopathy.
The authors concluded that the reliability of manual palpation tests in the assessment of LBP patients varies greatly. This is problematic because these tests are commonly used by manual therapists and clinicians. Little is known about the validity of these tests; therefore, their clinical utility is uncertain. High quality validity studies are needed to inform the clinical use of manual palpation tests.
I have repeatedly drawn attention to the fact that the diagnostic methods used by chiropractors and osteopaths are of uncertain or disproven validity (see for instance here, or here). Why is that important?
Imagine you consult a chiropractor or osteopath. Simply put, this is what is likely to happen:
- They listen to your complaint.
- They do a few tests which are of dubious validity.
- They give you a diagnosis that is meaningless.
- They treat you with manual therapies that are neither effective nor safe.
- You pay.
- They persuade you that you need many more sessions.
- You pay regularly.
- When eventually your pain has gone away, they persuade you to have useless maintenance treatment.
- You pay regularly.
In a nutshell, they have very little to offer … which explains why they attack everyone who dares to disclose this.
Cannabis seems often to be an emotional subject where more heat than light is generated. Does it work for chronic pain? This cannot be such a difficult question to answer definitively. Yet, systematic reviews have provided conflicting results due, in part, to limitations of analytical approaches and interpretation of findings.
A new systematic review is therefore both necessary and welcome. It aimed at determining the benefits and harms of medical cannabis and cannabinoids for chronic pain. Included were all randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1-month follow-up.
A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer-related pain (n=4). Length of follow-up ranged from 1 to 5.5 months.
Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of −0.50 cm (95% CI −0.75 to −0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of −0.35 cm (−0.55 to −0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect).
The authors concluded that moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo.
This is a high-quality review. Its findings will disappoint the many advocates of cannabis as a therapy for chronic pain management. The bottom line, I think, seems to be that cannabis works but the effect is not very powerful, while we have treatments for managing chronic pain that are both more effective and arguably less risky. So, its place in clinical routine is debatable.
Cannabis is, of course, a herbal remedy and therefore belongs to so-called alternative medicine (SCAM). Yet, I am aware that the medical cannabis preparations used in most studies are based on single cannabinoids which makes them conventional medicines.
Diabetic polyneuropathy is a prevalent, potentially disabling condition. Evidence-based treatments include specific anticonvulsants and antidepressants for pain management. All current guidelines advise a personalized approach with a low-dose start that is tailored to the maximum response having the least side effects or adverse events. Homeopathy has not been shown to be effective, but it is nevertheless promoted by many homeopaths as an effective therapy.
This study assessed the efficacy of individualized homeopathic medicines in the management of diabetic polyneuropathy. A multi-centric double-blind, placebo-controlled, randomized clinical trial was conducted by the Indian Central Council for Research in Homoeopathy at six centers with a sample size of 84. Based on earlier observational studies and repertorial anamnesis of DDSP symptoms 15 homeopathic medicines were shortlisted and validated scales were used for evaluating the outcomes post-intervention. The primary outcome measure was a change in Neuropathy Total Symptom Score-6 (NTSS-6) from baseline to 12 months. Secondary outcomes included changes in peripheral nerve conduction study (NCS), World Health Organization Quality of Life BREF (WHOQOL-BREF) and Diabetic Neuropathy Examination (DNE) score at 12 months.
Data of 68 enrolled cases were considered for data analysis. A statistically significant difference (p<0.014) was found in NTSS-6 post-intervention in the Verum group. A positive trend was noted for the Verum group as per the graph plotted for DNE score and assessment done for NCS. No significant difference was found between the groups for WHOQOL-Bref. Out of 15 pre-identified homeopathic medicines, 11 medicines were prescribed in potencies in ascending order from 6C to 1M.
The authors refrain from drawing conclusions about the efficacy of their homeopathic treatment (which is more than a little odd, as their stated aim was to assess the efficacy of individualized homeopathic medicines in the management of diabetic polyneuropathy). So, please allow me to do it for them:
The findings of this study confirm that homeopathy is a useless treatment.
Homeopaths believe that their remedies work for every condition imaginable and that naturally includes irritable bowel syndrome (IBS). But what does the evidence show?
The aim of this pilot study was to evaluate the efficacy of individualized homeopathic treatment in patients with IBS. The study was carried out at the National Homeopathic Hospital of the Secretary of Health, Mexico City, Mexico and included 41 patients: 3 men and 38 women, mean age 54 ± 14.89 years, diagnosed with IBS as defined by the Rome IV Diagnostic criteria. Single individualized homeopathics were prescribed for each patient, taking into account all presenting symptoms, clinical history, and personality via repertorization using RADAR Homeopathic Software. The homeopathic remedies were used at the fifty-millesimal (LM) potency per the Mexican Homeopathic Pharmacopoeia starting with 0/1 and increasing every month (0/2, 0/3, 0/6). Severity scales were applied at the beginning of treatment and every month for 4 months of treatment. The evaluation was based on comparing symptom severity scales during treatment.
The results demonstrated that 100% of patients showed some improvement and 63% showed major improvement or were cured. The study showed a significant decrease in the severity of symptom scores 3 months after the treatment, with the pain score showing a decrease already one month after treatment.
The authors state that the results highlight the importance of individualized medicine regimens using LM potency, although the early decrease in pain observed could also be due to the fact that Lycopodium clavatum and Nux vomica were the main homeopathic medicine prescribed, and these medicines contain many types of alkaloids, which have shown significant analgesic effects on pain caused by physical and chemical stimulation.
Where to begin?
Let me mention just a few rather obvious points:
- A pilot study is not for evaluating the efficacy, but for testing the feasibility of a definitive trial.
- The study has no control group, therefore the outcome cannot be attributed to the treatment but is most likely due to a mixture of placebo effects, regression towards the mean, and natural history of IBS.
- The conclusions are not warranted.
- The paper was published in the infamous Altern Ther Health Med.
Just to make sure that nobody is fooled into believing that homeopathy might nonetheless be effective for IBS. Here is what the Cochrane review on this subject tells us: no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy for IBS compared to placebo or usual care.
In my view, even the conclusion of the Cochrane review is odd and slightly misleading. The correct conclusion would have been something more to the point:
THE CURRENT TRIAL EVIDENCE FAILS TO INDICATE THAT HOMEOPATHY IS AN EFFECTIVE TREATMENT FOR IBS.
The authors of this review start their paper with the following statement:
Acupuncture has demonstrated effectiveness for symptom management among breast cancer survivors.
This, I think, begs the following question: if they already know that, why do they conduct a systematic review of the subject?
The answer becomes clear as we read thier article: they want to add another paper to the literature that shows they are correct in their assumption.
So, they do the searches and found 26 trials (2055 patients), of which 20 (1709 patients) could be included in the meta-analysis. Unsurprisingly, their results show that acupuncture was more effective than control groups in improving pain intensity [standardized mean difference (SMD) = -0.60, 95% confidence intervals (CI) -1.06 to -0.15], fatigue [SMD = -0.62, 95% CI -1.03 to -0.20], and hot flash severity [SMD = -0.52, 95% CI -0.82 to -0.22]. Compared with waitlist control and usual care groups, the acupuncture groups showed significant reductions in pain intensity, fatigue, depression, hot flash severity, and neuropathy. No serious adverse events were reported related to acupuncture intervention. Mild adverse events (i.e., bruising, pain, swelling, skin infection, hematoma, headache, menstrual bleeding) were reported in 11 studies.
The authors concluded that this systematic review and meta-analysis suggest that acupuncture significantly reduces multiple treatment-related symptoms compared with the usual care or waitlist control group among breast cancer survivors. The safety of acupuncture was inadequately reported in the included studies. Based on the available data, acupuncture seems to be generally a safe treatment with some mild adverse events. These findings provide evidence-based recommendations for incorporating acupuncture into clinical breast cancer symptom management. Due to the high risk of bias and blinding issues in some RCTs, more rigorous trials are needed to confirm the efficacy of acupuncture in reducing multiple treatment-related symptoms among breast cancer survivors.
Yes, I agree: this is an uncritical white-wash of the evidence. So, why do I bother to discuss this paper? After all, the acupuncture literature is littered with such nonsense.
Well, to my surprise, the results did contain a little gem after all.
A subgroup analysis of the data indicated that acupuncture showed no significant effects on any of the treatment-related symptoms compared with the sham acupuncture groups.
Acupuncture seems to be a placebo therapy!
Acupuncture is usually promoted as a safe therapy. This may be good marketing but, sadly, it is not the truth. About 10% of all patients experience mild to moderate adverse effects such as pain or bleeding. In addition, there are well-documented complications, for instance:
However, there have been few reports of deaths due to pneumothorax after acupuncture treatment, especially focused on electroacupuncture.
Japanese authors recently reported an autopsy case of a man in his 60s who went into cardiopulmonary arrest and died immediately after receiving electroacupuncture. Postmortem computed tomography (PMCT) showed bilateral pneumothoraces, as well as the presence of numerous gold threads embedded subcutaneously. An autopsy revealed two ecchymoses in the right thoracic cavity and a pinhole injury on the lower lobe of the right lung, suggesting that the needles had penetrated the lung. There were marked emphysematous changes in the lung, suggesting that rupture of bullae might also have contributed to bilateral pneumothoraces and fatal outcomes. The acupuncture needles may have been drawn deeper into the body than at the time of insertion due to electrical pulses and muscle contraction, indicating the need for careful determination of treatment indications and technical safety measures, such as fail-safe mechanisms.
This is the first case report of fatal bilateral pneumothoraces after electroacupuncture reported in the English literature. This case sheds light on the safety of electroacupuncture and the need for special care when administering it to patients with pulmonary disease who may be at a higher risk of pneumothorax. This is also the first report of three-dimensional reconstructed PMCT images showing the whole-body distribution of embedded gold acupuncture threads, which is unusual.
One-sided pneumothoraxes are common events after acupuncture. Several hundred cases have been published and the vast majority of such incidents remain unpublished or even unnoticed. These events are not normally life-threatening. If ‘only’ one lung is punctured, the patient may experience breathing difficulties, but in many cases these are temporary and the patient soon recovers.
Yet a bilateral pneumothorax is an entirely different affair. If both lungs malfunction, the patient’s chances of survival are slim unless he/she is close to an intensive care unit.
You might think that it needs an especially ungifted acupuncturist to manage to puncture both lungs simultaneously. I might agree, but we need to consider that acupuncture needles are often inserted in a symmetrical fashion into the patient’s body. This means that, if the therapist puts a needle at one point of the thorax that is close to a lung, he is not unlikely to do the same on the other side.
And how does one prevent such disasters?
- train acupuncturists properly,
- avoid needles on the upper thorax,
- or refuse acupuncture altogether.
In their 2019 systematic review of spinal manipulative therapy (SMT) for chronic back pain, Rubinstein et al included 7 studies comparing the effect of SMT with sham SMT.
They defined SMT as any hands-on treatment of the spine, including both mobilization and manipulation. Mobilizations use low-grade velocity, small or large amplitude passive movement techniques within the patient’s range of motion and control. Manipulation uses a high-velocity impulse or thrust applied to a synovial joint over a short amplitude near or at the end of the passive or physiological range of motion. Even though there is overlap, it seems fair to say that mobilization is the domain of osteopaths, while manipulation is that of chiropractors.
The researchers found:
- low-quality evidence suggesting that SMT does not result in a statistically better effect than sham SMT at one month,
- very low-quality evidence suggesting that SMT does not result in a statistically better effect than sham SMT at six and 12 months.
- low-quality evidence suggesting that, in terms of function, SMT results in a moderate to strong statistically significant and clinically better effect than sham SMT at one month. Exclusion of an extreme outlier accounted for a large percentage of the statistical heterogeneity for this outcome at this time interval (SMD −0.27, 95% confidence interval −0.52 to −0.02; participants=698; studies=7; I2=39%), resulting in a small, clinically better effect in favor of SMT.
- very low-quality evidence suggesting that, in terms of function, SMT does not result in a statistically significant better effect than sham SMT at six and 12 months.
This means that SMT has effects that are very similar to placebo (the uncertain effects on function could be interpreted as the result of residual de-blinding due to a lack of an optimal placebo or sham intervention). In turn, this means that the effects patients experience are largely or completely due to a placebo response and that SMT has no or only a negligibly small specific effect on back pain. Considering the facts that SMT is by no means risk-free and that less risky treatments exist, the inescapable conclusion is that SMT cannot be recommended as a treatment of chronic back pain.
This systematic review assessed the effect of spinal manipulative therapy (SMT), the hallmark therapy of chiropractors, on pain and function for chronic low back pain (LBP) using individual participant data (IPD) meta-analyses.
Of the 42 RCTs fulfilling the inclusion criteria, the authors obtained IPD from 21 (n=4223). Most trials (s=12, n=2249) compared SMT to recommended interventions. The analyses showed moderate-quality evidence that SMT vs recommended interventions resulted in similar outcomes on
- pain (MD -3.0, 95%CI: -6.9 to 0.9, 10 trials, 1922 participants)
- and functional status at one month (SMD: -0.2, 95% CI -0.4 to 0.0, 10 trials, 1939 participants).
Effects at other follow-up measurements were similar. Results for other comparisons (SMT vs non-recommended interventions; SMT as adjuvant therapy; mobilization vs manipulation) showed similar findings. SMT vs sham SMT analysis was not performed, because data from only one study were available. Sensitivity analyses confirmed these findings.
The authors concluded that sufficient evidence suggest that SMT provides similar outcomes to recommended interventions, for pain relief and improvement of functional status. SMT would appear to be a good option for the treatment of chronic LBP.
In 2019, this team of authors published a conventional meta-analysis of almost the same data. At this stage, they concluded as follows: SMT produces similar effects to recommended therapies for chronic low back pain, whereas SMT seems to be better than non-recommended interventions for improvement in function in the short term. Clinicians should inform their patients of the potential risks of adverse events associated with SMT.
Why was the warning about risks dropped in the new paper?
I have no idea.
But the risks are crucial here. If we are told that SMT is as good or as bad as recommended therapies, such as exercise, responsible clinicians need to decide which treatment they should recommend to their patients. If effectiveness is equal, other criteria come into play:
Can any reasonable person seriously assume that SMT would do better than exercise when accounting for costs and risks?
I very much doubt it!