138 e-Letters

  • Perrier et al a deeply flawed study on Conflict of Interests in Homeopathy meta-analyses

    We read with interest the study by Perrier et al on the Relationship between the conflicts of interest and the results of meta-analyses of homoeopathy trials. We want to briefly address issues we see with this paper.
    Firstly, the criteria for a study presenting a Conflict of Interest (CoI) include that a single author has a link with any research institution involved in homeopathy research. Translated to other fields of research, Oncology for example, this would mean that cancer studies emanating from Cancer Research institutes would have to be considered as conflicted and therefore unreliable. This is clearly an absurd way of defining CoIs.
    More importantly, the authors wrongly report the Odds Ratio (OR) data for the Shang et al paper as being OR = 0.88, CI 0.65-1.19, N=105, this OR corresponds to the N=8 ‘larger high-quality trials’ from that study, not N=105. The OR for N=105 was never published but the OR for the N=21 ‘high-quality trials’ is OR = 0.76; CI: 0.59-0.99, N=21 (Ludtke & Ruttem 2008). Ignoring the meaningless N=1 MAs in Fig 1, we end up with three CoI-free MAs, which all favour homeopathy. And this trend would only be accentuated by using the correct OR for the full N=105 trials. The overall picture painted by the data is thereby very different than reported by the authors. In particular there appears to be no statistical difference between their so-called CoI and CoI-free MAs in Homeopathy.

  • Moving Forward on HPV Vaccine Safety Concerns

    Gøtzsche and Jørgensen claim that the European Medicines Agency (EMA) mishandled their investigation of the safety of the HPV vaccine regarding serious neurological adverse events from the administration of the HPV vaccine, such as postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The authors highlight the insufficiency due to poor data analysis, conflicts of interest, poor research into aluminum adjuvants, and bias in analyzing the research 1. We want to discuss several key points on the safety of the HPV vaccine.
    Over 270 million doses of HPV vaccines have been administered since 2006. Many regulatory agencies have overseen the safety of the HPV vaccine, including the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) 2. Most regulatory agencies regard the HPV vaccine as safe and effective 3,4. The noted exception in this article is the Uppsala Monitoring Centre which identified safety signals for POTS and CRPS post-HPV vaccination 5.
    As of specific note from the paper, the majority of the evidence supporting an association with the HPV vaccine and POTS and CRPS in the article by Gøtzsche and Jørgensen was generated from data in Europe, including Denmark 1. A recent study showed no safety signal generally and specifically commented that the Denmark signal was not identified in their analysis, noting that 1,232,572 girls received the vaccine and 563 unique CRPS diagnoses (6). Concerns about...

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  • Controlled but not placebo controlled

    It is misleading (as stated in “what this study adds”) to described this trial as placebo controlled. Although dummy capsules were used to blind participants to which combination of curcumin or omeprazole they were receiving, no group received placebo only. One interpretation of the findings therefore remains that they are due to a placebo effect. It is unfortunate that this misrepresentation of the study design has already been picked up by a UK National newspaper (Guardian 12 September)

  • Addressing the Challenges in Researching Long- and Post COVID

    Dear Editor,

    we are writing in response to the article titled " How methodological pitfalls have created widespread misunderstanding about long COVID”(1).

    We agree with the authors, that the existing epidemiological research on long COVID has suffered from overly broad case definitions and a striking absence of control groups, which may have led in an overestimation of risk.
    It is important to acknowledge that Long- and Post-COVID syndrome are heterogeneous conditions, likely comprising different pathomechanistic groups such as autoimmunity, mitochondrial dysfunction, and virus persistence (2). This complexity, coupled with the lack of routine biomarkers, makes it difficult to accurately define and study this condition. Høeg et al et al. therefore raise some relevant points regarding the challenges faced in studying Long- and Post-COVID syndrome, particularly the need for properly matched control groups and internationally-established diagnostic criteria. Regarding the latter, the authors of the article themselves fail to use definitions accurately, particularly in distinguishing between the now consented WHO definitions of Long-COVID and Post-COVID (WHO/2019-nCoV/Post_COVID-19_condition/Clinical_case_definition/2021.1).
    It is true, that initial studies depicted a high prevalence of Post-COVID syndrome (PCS). However, more recent population-based studies present a different perspective. In assessing the clinical picture, the primary focus isn...

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  • Inconsistencies in "Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial".

    Dear Editor,

    With great interest I read the original research article “Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial” by Kongkam et al. While the authors suggest that the study demonstrates that the efficacy of curcumin for functional dyspepsia is comparable to that of omeprazole, I want to point out some deficiencies and discrepancies of the study reporting that cast doubt on this conclusion.

    Firstly, it is not clear what hypothesis was tested and what specific study results the conclusion is based on. The main outcomes are vaguely specified as functional dyspepsia symptoms. As the equivalence design is mentioned, the reference to improvement of 2 points in the SODA score between the treatment group should probably be interpreted as the equivalence margin set for the study. The results of nine pairwise comparisons are provided in Table 3. For three of them 95% confidence intervals include the equivalence margin, thus clearly demonstrating non-equivalency. For example, for pain intensity in curcumin only vs omeprazole only arms the 95% CI is −1.16 (−2.95 to 0.64), which demonstrates that curcumin is not non-inferior to omeprazole.

    To add to the issue of unclear study question and selective post hoc interpretation of outcomes, it should be mentioned that the study was not registered prospectively. The TCTR registration (TCTR20221208003) is post factum. Also the authors do not properly explain...

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  • Understanding each other

    I read this scoping review with great interest. In linguistics there is a term for the phenomenon that a word can have the capacity to have multiple related meanings in different contexts. This term is polysemy. In the context of defining "Evidence-based medicine". If we want to understand each other, it proved successful to define the words we use .Sackett et al. in their seminal article about" EBM what it is and what it isn't" also defined what they mean by "evidence", namely: "By best available external clinical evidence we mean clinically relevant research,often from the basic sciences of medicine, but especially from patient centred clinical research into the accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic markers, and the efficacy and safety of therapeutic, rehabilitative, and preventive regimens."
    Doesn't this render it irrelevant for the context of EBM if others define differently in other contexts? A bigger problem arises when the term evidence is misunderstood or even misused within the context of EBM. This problem might be approached by better teaching of the meaning originally meant. Evidence to my knowledge (as a non-english native speaker) is a juridical term and thus different to proof or fact. Juridically only the sum of evidence is leading to a court decision. And, this decision can be wrong especially if new evidence arises.

  • What actually happened to 'R' in March 2020 as a result of school closures in the UK??

    The article by Alastair Munro and colleagues (to which this is a rapid response) is of great value and importance, as we can now see, since this article was published, that there has been considerable discussion and interrogation by the COVID inquiry (https://covid19.public-inquiry.uk/), about whether the closure of schools, ordered on 18th March 2020 by Boris Johnson's government, and put into effect two days later on 20th March, was ever necessary.

    The rationale for the closure of schools was that it was imperative that the transmission rate of the COVID-19 pandemic, then rapidly spreading in the UK, was brought down at pace. Only three days later, a full, mandated, "lock down" was imposed. This was in the context of a suite of increasingly draconian measures to impose Non-Pharmaceutical Interventions (NPIs) on an increasingly fretful population - on March 12th, 16th, 20th and 23rd.

    The question we pose of the authors of the current paper under discussion is a simple one. What is the actual, real world, evidence that the 'R' value fell as a result of the closure of schools? Is there any real-world, UK-based, 2020 information we can use to answer this question. This question cannot remotely be answered by reference to other countries, or, to mathematical models. The impact of school closures must also be analysed independently of all of the other contemporaneous NPIs.

    If the o...

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  • Health & equitable healthcare is a human right

    Health & healthcare is a human rights issue. Persons with intellectual disabilities use disproportionately more health care resources than the population without intellectual disabilities. In spite of this, they experience poorer health outcomes and they and their carers are significantly less satisfied with the quality of care provided to them by a variety of healthcare personnel. This can include doctors, pharmacists, nurses and other personnel.

    The right to health contains freedoms. These freedoms include the right to be free from non-consensual medical treatment, such as medical experiments and research or forced sterilization, and to be free from torture and other cruel, inhuman or degrading treatment or punishment.

    The right to health also contains entitlements. These entitlements include among others:   The right to a system of health protection providing equality of opportunity for everyone to enjoy the highest attainable level of health; The right to prevention, treatment and control of diseases; Equal and timely access to basic health services; The provision of health-related education and information; Equal and timely access to basic health services etc.

    Human rights are interdependent, indivisible and interrelated. This means that violating the right to health may often impair the enjoyment of other human rights, such as the rights to education or work, and vice versa. Persons with disabilities face various challenges to the enjoy...

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  • Re: Ecological study estimating melanoma overdiagnosis in the USA using the lifetime risk method

    February 28, 2024

    To: Juan VA Franco, MD
    British Medical Journal, Evidence-Based Medicine

    Dear Editor:
    The study on cutaneous melanoma overdiagnosis attempts to tackle an important issue. However, we wish to address several methodological concerns that may warrant a critical evaluation of its conclusions.

    First, one key study assumption is that the overdiagnosis of melanoma is due to over-screening by clinicians, including dermatologists. However, whether the patients were actually screened by clinicians is unknowable with the current study design. Thus, the lack of direct evidence to support this key assumption limits the study's capacity to attribute melanoma diagnoses to the prevalence of screening.

    Second, the study's ecological methodology does not sufficiently account for variables that could affect melanoma diagnosis and mortality rate over time, such as advancements in diagnostic technologies, treatments, public awareness, and healthcare access, all factors that dermatologists have worked to improve over time. These factors could independently influence trends in melanoma incidence and mortality. This limitation is critical as it underlines the difficulty in drawing definitive conclusions from the ecological data presented.

    Thirdly, the choice to manually input annual data from the SEER program into the DevCan software, deviating from the standard 3-year data aggregatio...

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  • What about acces to innovative radiopharmaceutical l products

    As French Nuclear Medicine representatives, we read with great interest the article by Le Guludec et al. entitled: Rapid access to innovative medicinal products while ensuring relevant health technology assessment: Position of the French National Authority for Health. In this interesting and important position paper from the French Independent Health Technology body (HTAb) called “Haute Autorité de Santé” (HAS), the authors state that its recommendations derive from consultations with academics. Although we understand that accessibility to innovative drugs used for Positron Emission Tomography (PET) could be considered as a very ancillary issue by the HAS board that authored the paper, these PET imaging molecules are still considered as medicinal products from a regulatory standpoint and should be evaluated as such.
    We regret that, to our knowledge, none of the academic members of the French Nuclear Medicine Society (SFMN) board were given the opportunity to draw attention to some of the specific features of the drugs commonly used in nuclear medicine by answering the questionnaire sent to the panelists (cf supplemental material). Indeed, we would clearly have answered “Yes” to the following questions:
    - Are there specific methodological issues for Health Technology Assessment you wish to bring to our attention?
    - Do you identify methodological issues relative to the assessment of innovative drugs in specific therapeutic areas?
    We would also have be...

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