eLetters

108 e-Letters

  • Rapid Response, BMJ Evidence-Based Medicine

    Rapid Response, BMJ Evidence-Based Medicine
    Re: Popp M, Kranke P, Meybohm P, et al. Evidence on the efficacy of ivermectin for covid-19: another story of apples and oranges. BMJ Evidence-Based Medicine Published Online First: 20 August 2021. doi: 10.1136/bmjebm-2021-111791

    Ivermectin in Covid-19

    Andrew Bryant MSc
    Population Health Sciences Institute, Newcastle University
    Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne NE2 4AX, UK
    Email: andy.bryant@ncl.ac.uk
    Theresa A Lawrie MBBCh PhD
    Edmund J Fordham PhD FInstP
    EbMCsquared, a Community Interest Company
    Northgate House, Upper Borough Walls, Bath BA1 1RG, UK
    Scott Mitchell MBChB MRCS
    Emergency Department, Princess Elizabeth Hospital, Guernsey

    To the Editor
    The sole substantive critique in this Letter[1] is the description of Bryant[2] et al. (hereafter “Bryant”) as a “bowl of colourful fruit salad”[1], because of the pre-specified comparison of “ivermectin” vs “no ivermectin”. Trials with (potentially) active comparators were indeed included. Reflection should show that any bias is conservatively against ivermectin. Helpful control interventions would dilute the apparent benefit of ivermectin, relative to inactive comparators exclusively. Efficacy will be understated, not overstated, with respect to controls.
    Unsuspected active agents in ivermectin combination therapies might...

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  • RE: Is there a smoker’s paradox in COVID-19?

    There is a hypothesis that nicotine may have a protective effect in COVID-19 (1). I present two recent reports on the association between smoking and COVID-19 infection/progression, and then presented reports regarding another mechanism of the association.

    Paleiron et al. conducted a cross-sectional study to investigate the association between smoking and COVID-19 (2). The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of current smokers and subjects aged over 50 years for the risk of developing Covid-19 were 0.64 (0.49-0.84) and 2.6 (1.2-6.9), respectively. Smoking presented a protective effect on the developing COVID-19.

    Farsalinos et al. conducted a meta-analysis to examine the effects of current smoking on adverse outcomes among hospitalized COVID-19 patients (3). Pooled OR (95% CI) of current smokers against non-current smokers and against former smokers for adverse outcomes was 1.53 (1.06-2.20) and 0.42 (0.27-0.74), respectively. Smoking relates to the progression of clinical outcomes in hospitalized COVID-19 patients, although the reason of poor clinical outcomes in former smokers should be explored by further studies.

    There is another hypothesis that lithium will limit SARS-CoV2 infections. Rudd presented a hypothesis that the repurposing of low-cost inhibitors of glycogen synthase kinase-3 (GSK-3) such as lithium will limit SARS-CoV2 infections by both reducing viral replication and potentiating the immune response against the vi...

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  • NICE Response to: NICE rapid guidelines: exploring political influence on guidelines

    In their article McPherson and Speed claim that NICE’s independence seems to have diminished over time, and that it has been significantly undermined during the COVID-19 pandemic. They attempt to explain how various soft political factors may operate and how they undermine NICE’s scientific integrity.

    The authors begin by suggesting that NICE’s re-establishment as a non-departmental public body (NDPB) in 2013 was prompted by the need to “increase the deniability of rationing claims or for other political purposes”.
    Rather surprisingly, the authors then go on to claim that:
    “This revision to the relationship can be regarded as a move towards a more explicit form of meta-governance, whereby government mechanisms are enacted through a range of quasi-autonomous bureaucratic devices.”
    and further that:

    “decisions about access to healthcare, for example, can be made remotely from ministers and political motive obscured by claims of the need for availability to be determined by science, not politics."

    These statements are baffling because the legal position is clear. As a statutory corporation NICE is more, rather than less, independent as an arms length body (ALB) and as a body subject to administrative law and the administrative court, NICE is positively required as a matter of law to reach its decisions independently. If it did not do so its decision would be subject to being overturned by the courts. Furthermore, the regulations...

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  • Consideration of the need for diversity in point-of-care ultrasound research design

    To the Editor,

    We read with great interest the recent publication by Prager et al in BMJ Evidence-Based Medicine (1) and commend the authors on their important work. The authors characterize blinding practices in point-of-care ultrasound (POCUS) diagnostic accuracy clinical research. The authors evaluated whether the interpreter was blinded to patient clinical information in articles published in Emergency Medicine, Anesthesia, and Critical Care journals from January 2016 to 2020. Among 97 studies, the authors found that the POCUS interpreter was blinded to clinical information in 38.1% of studies, not blinded in 35.1%, and that the blinding practice was not reported in 26.8%. They additionally report that the same person obtained and interpreted images in 74.2% of studies, was different in 14.4%, and was not reported in 11.3%. These results demonstrate significant variability in POCUS research, leading the authors to conclude that to ensure generalizability of future research, the same person should perform and interpret the POCUS scan and not be blinded to clinical information.

    The authors are firm in their recommendation and its perceived benefit. We believe, however, that it is short-sighted to uniformly recommend a study design in this rapidly evolving field. The authors (and importantly, future researchers) should carefully weigh the advantages and disadvantages of differing study designs. Both blinding and not blinding to clinical information allow co...

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  • RN. BSN

    It would be helpful if it assessed the standard administration quantitatively and specific frequency utilized in the study ‘s participants , or related studies , At the very least - providing a link to the exact dosing used in this study as a reference point would be beneficial .

  • Interaction of non-enzyme-inducing antibiotics with hormonal contraceptives

    Drs Clure and Lazorwitz have misunderstood and misinterpreted the Yellow Card data that we adduced to test the null hypothesis that there is no interaction of antibiotics with hormonal contraceptives. Here we reply to their specific comments.

    “The medications in each group are not equivalent and bias the sample” We chose a wide range of medicines in order to minimize this. Clure and Lazorwitz have selected only two examples each from the group of nine control drugs and the group of nine non-enzyme-inducing antibiotics, and assert that the age distribution favours older women in the control group. However, they ignore the fact that the same could be asserted of the enzyme-inducing drugs, some of which are more likely to be used in older women, but had an even bigger effect than the antibiotics.

    “The rates of unintended pregnancy reported … are much lower than expected in general users of oral contraception” This is an important misunderstanding, which we sought to obviate in the paper, by making it clear that the data do not allow calculation of the absolute rates of unintended pregnancies. That is because the reported rates are not rates of unintended pregnancies in women taking hormonal contraceptives, but the frequencies of reports of unintended pregnancies as a proportion of all reports of suspected adverse reactions. It is the ratios of frequencies that are important. In other words, whatever the baseline risk is, the risk is 13 times higher with enzyme i...

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  • Low carbohydrate diet SHOULD be recommended for patients diagnosed with familial hypercholesterolaemia and metabolic syndrome

    Pawlak1 critiqued our challenge to conventional dietary guidelines for people diagnosed with familial hypercholesterolaemia (FH)2. Indeed, his criticism was so incriminatory that he stated our recommendation “constitutes malpractice”. Considering the gravity of his claim, especially as it is levied against co-authors who are mostly MDs, it is important to disclose what we actually recommended, and to point out the flawed evidence Pawlak used to claim that we have committed malpractice.

    First, Pawlak misunderstood the purpose of our paper. We did not question “the efficacy of low-saturated fat, low-cholesterol diet to reduce LDL cholesterol”, as he stated. We provided strong support for the hypothesis that factors other than LDL-C, such as smoking, hypercoagulation and hyperinsulinemia, have a potent influence on the incidence of coronary events in FH that dwarfs that of LDL-C3. For example, in our Figure 4 we illustrated the findings of Gaudet et al.4, who demonstrated that FH people without obesity or insulin resistance had no greater rate of coronary heart disease (CHD) than non-FH people. In contrast, obese, insulin-resistant FH people had over 7 times greater incidence of CHD than non-FH people. Moreover, in recent work we have elaborated on the extensive, but largely ignored, literature demonstrating that factors other than LDL-C, such as increased levels of coagulation factors, explain why only a subset of FH individuals develop premature CHD5. Finally, we in...

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  • The issues with promoting honey over antibiotics

    To the editor,

    We read the article “Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis” with great interest. The need to discover effective remedies for symptomatic relief of upper respiratory tract infections (URTIs), while preventing further antimicrobial resistance developing is indeed paramount. However, after reading the article in detail, we noted a number of discrepancies which we feel must be highlighted and addressed.

    Firstly, we believe that the article is misleading, and if read as a lay member of the public, or indeed by a sensationalist news outlet, incorrect and potentially health-threatening conclusions may be drawn and promoted. Firstly, the abstract focuses on positing honey as an alternative to antibiotics for the symptomatic relief of URTIs. The authors highlight that honey possesses antimicrobial properties, with the conclusion of the abstract affirming that it is a “widely available and cheap alternative to antibiotics”. The abstract also concludes that honey improves symptoms in comparison with “usual care”, which, left hitherto unspecified, and paired with the aforementioned focus on a comparison between honey and antibiotics, again augments the misleading introduction to the article. Fundamentally, none of the 14 the studies included within the systematic review compare the use of honey with the use of antibiotics. Focusing so strongly on comparing honey to antib...

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  • Caffeine and pregnancy: The need for calm reflection. Reply to Murphy et al.

    The Murphy et al. letter1 is notable for its ad hominem claims, the first of which comes in their introductory remarks. Noting that my review2 reports no conflicts of interest, they make the exaggerated claim that I have “written extensively on the ‘lethality’ of caffeine”. That claim cites one published article, titled “Death by Caffeine”,3 which summarises reports of death by poisoning involving documented cases from coronial and other official public inquiries. As reported in that article, official records in several countries report multiple confirmed cases of death by poisoning due to caffeine. Although relatively rare, such cases have been (and continue to be) reported worldwide. Predicated on the mere fact that I have previously reported findings from official inquiries into caffeine-related harm, the claim by Murphy et al. of “conflict” is perverse. By implication, their reasoning would mean that the reporting of harm from any source (which includes much of the content of medical journals) renders authors (i.e., most medical researchers) evermore vulnerable to bias warranting formal disclosure of conflict of interest in all future reports on the same or related topic. Of course, no such custom or practice exists.

    Notably, the assertion of conflict in this instance indicates poor understanding of the matter, a lamentable situation considering the professional identities of Murphy and her 20 co-authors. Conflict of interest arises when a primary interest conf...

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