51 e-Letters

published between 2018 and 2021

  • 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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  • Caffeine and pregnancy: Advice to women. Reply to Castanyer

    Dr Castanyer1 wonders about the soundness of the advice she gives her patients about the reputed safety of moderate caffeine consumption during pregnancy. Her concerns regarding current clinical practice warrant consideration. I agree that “aging or prior medical history may act as confounders of negative pregnancy outcomes”. As reported in the review,2 numerous potential confounders have been examined (and often re-examined many times), including “diverse demographic variables, behaviour patterns, and living environment . . . age at conception, health status, pregnancy history, use of oral contraceptives, alcohol and other substance use, exposure to pollutants, maternal body mass, physical activity, religion, education, and occupation . . . pregnancy symptoms . . . potential recall bias and maternal cigarette smoking” (p. 5).2 However, as also reported in the review, caffeine-related negative pregnancy outcomes have repeatedly proven “robust to threats from potential confounding”.

    In addition, Dr Castanyer suggests that any “change of medical recommendation” should await the outcome of randomised clinical trials. Again, that option is examined in the review, which includes a section headed, “Are Randomized Controlled Trials the Solution?” (pp. 5-6).2 However, as reported in the review, beyond the single trial conducted to date,3 it is doubtful whether mooted clinical trials will proceed due to ethical concerns over exposing pregnant women to caffeine, even at reput...

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  • Caffeine and pregnancy: Don’t shoot the messenger, please. Reply to Fernando

    Dr Fernando’s1 concerns about potential confounding from alcohol consumption and smoking do not warrant comment here as they are addressed in my review2 and summarised in my letter of reply to Murphy et al.3 A separate concern, shared by O’Connor4 and Murphy et al.,3 reveals Dr Fernando’s misguided presumption that narrative review is not “proper”. More specifically, while claiming that “a significant number of studies will have been missed” by my review, he cites no actual examples of publications he believes should have been included.

    Additionally, along with O'Connor4 and Murphy et al.,3 Dr Fernando believes that prior publication renders authors biased when writing again on the same or similar topic. Pursuing the point, he injects an impugning embellishment regarding his claimed “insight into the motives of the author”. He refers to two books “about the dangers of caffeine”, a description that misrepresents the contents of those books and is a thinly veiled attempt at disparagement. The books are titled Caffeine and Health (1991)5 and Understanding Caffeine: A Biobehavioral Analysis (1997),6 respectively. Neither book is “about the dangers of caffeine”. On the contrary, both books seek to provide a comprehensive evidence-based biopsychosocial account of the most widely-consumed psychoactive substance in history, including reputed harms and benefits.

    Dr Fernando finds it “interesting” that my review contains a description of just “one randomised contr...

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  • Caffeine and Pregnancy: Bias? Is this a case of the pot calling the kettle black? Reply to O'Connor

    Dr O’Connor1 is concerned that I have published previous reviews, and in so doing may be biased. Indeed, I have published previous reviews, and my familiarity with the relevant literature has led me increasingly to question current relaxed attitudes towards caffeine consumption during pregnancy. The first review, published in 1985,2 reported that evidence available at that time tentatively supported the conclusion that caffeine may contribute to foetal growth restriction and low birth weight. That review highlighted methodological shortcomings in the then extant literature, and called for more research employing improved methods for measuring caffeine exposure and better controls against potential confounders.

    An updated review, in 1991,3 found that more and improved research had been published since the earlier review, and that the overall evidence of caffeine-related negative pregnancy outcomes had strengthened. With a subsequent update in 1997,4 it was concluded that the evidence against maternal caffeine consumption had become strong. The latest review5 reported that the balance of evidence, including findings from original observational studies and meta-analyses, supported the conclusion that consumption of caffeine during pregnancy increases the risk of several serious negative pregnancy outcomes. Perversely, Dr O’Connor appears to believe that familiarity with research implies bias. In fact, my conclusions evolved over time, and the direction of that evolutio...

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  • It remains unclear whether caffeine causes adverse pregnancy outcomes; but naive policy recommendations could cause harm.

    In his narrative review of the association between maternal caffeine consumption and pregnancy outcomes, Professor Jack E James claimed there was sufficient evidence of harmful causal effects to suggest that pregnant women or women contemplating pregnancy should 'avoid caffeine' (1). His opinions were widely reported by the media in line with a sensational press release that claimed there was "No safe level of caffeine consumption for pregnant women and would-be mothers". We do not however consider these claims to be appropriate or justified, due to a number of serious methodological limitations, statistical errors, and a concerning lack of objectivity. The author declared no conflicts of interest, yet has written extensively on the 'lethality' of caffeine (2). For this, and the following reasons, we believe the review and its recommendations should be interpreted with extreme caution.

    1. Scientific conduct
    a) The article is described as a ‘narrative review’, and thus by its nature, falls well short of the standards expected for a formal systematic scientific review of the literature. It is not clear how the author identified articles for inclusion, nor what criteria were used for exclusion, or what approach, if any, was used to critically appraise the studies identified or synthesise the information obtained. It is therefore difficult to have confidence that the articles presented offer an unbiased reflection of the literature an...

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  • Correcting the record: all studies of smokers with COVID-19 show a protective effect

    Usman et al (1) write that only one of the 18 studies of COVID-19 patients they included in their review of the Smoker's Paradox reported that "the prevalence of smokers resembles that of the general population."

    But this study--by Richardson et al in New York City (2)--actually only reported the prevalence of "never smokers" at 84.4%. It did not distinguish between current and former smokers among the remaining 15.6%, however, so Usman et al should have marked this combined result with an asterisk in their Table 1. Far from resembling the general population, the 15.6% combined rate is less than half the 34% expected in USA, where approximately 14% are current and 20% former smokers. With this correction, all 18 studies support the Smoker’s Paradox, which belies the authors’ conclusion that a “protective effect should NOT be inferred” [emphasis added].

    The protective effect is clearly real and further supported by the largest study of COVID-19 to date (n=7,162) with data on smoking status (3), which Usman et al did not include in their review. Current smokers in this CDC study comprised just 1.3% of all the COVID-19 patients seeking care from US hospitals in 50 states and Washington DC, 1.2% of those treated as outpatients, and 1.1% of those treated in intensive care units.

    Usman et al also did not mention the compound most likely responsible for the protective effects of smoking against respiratory infections, which...

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