eLetters

43 e-Letters

published between 2017 and 2020

  • 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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  • SARS-CoV-2 mimicry of an epithelial sodium ion channel (ENaC) linked to increased risk of severe COVID-19 symptoms in cigarette smokers

    Dear Editor,
    Recent literature suggested increased risk of severe COVID-19 in smokers which also got affirmation from World Health Organization (WHO) [1, 2]. However, original peer reviewed research which explained pathophysiological basis of the enhanced COVID-19 severity in smokers is currently scarce. Increased expression of SARS-CoV-2 cell entry receptor ACE2 in respiratory tract and lung tissue of smokers unraveled from analysis of gene expression data was used to predict higher chances of SARS-CoV-2 infection but that failed to explain enhanced COVID-19 severity [3]. Few authors have suggested that increased risk of severe complications and higher mortality rate in infected smokers may be due to host-specific factors like weakening of respiratory health and immunity caused by chronic smoking [4]. However, none of the virus-related factors which can be responsible for the COVID-19 severity in smokers has been reported until date. Based on the recent research updates on SARS-CoV-2 specific virulence in host cells, we propose a plausible mechanism which associates smoking with increased severity of COVID-19.
    Apart from a cell surface entry receptor, coronaviruses require furin (a host protease) mediated cleavage of their spike (S) protein for successful invasion of the host cell. SARS-CoV-2, a member of the genus betacoronaviruses, has evolved a unique furin protease S1/S2 cleavage site, which is absent in other family members, including SARS-CoV-1 [5]. Rec...

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  • Letter to the editor in response to “Analysis of reports of unintended pregnancies associated with the combined use of non-enzyme-inducing antibiotics and hormonal contraceptives”

    First available online on August 18, 2020 in BMJ Evidence-Based Medicine, Aronson and Ferner (1) concluded that women using hormonal contraceptives cannot rely on their contraceptive method if they take a short course of non-enzyme inducing antibiotics based on Yellow Card reports to the UK’s Medicines and Healthcare products Regulatory Agency.
    We believe that there are fundamental scientific issues and limitations with this study not adequately addressed by the authors. First, Yellow Card reports require provider reporting of an unintended pregnancy, which the authors acknowledge are subject to reporting bias. As the authors also acknowledge, many healthcare providers suspect there are drug-drug interactions between hormonal contraception and all antibiotics, despite the lack of definitive evidence (1). Therefore, there already exists a bias among providers that they would suspect and report an unintended pregnancy attributed to a drug-drug interaction among women taking antibiotics. The medications in each group are also not equivalent and bias the sample. For example, in the antibiotic group, metronidazole and nitrofurantoin are more commonly used in younger reproductive-aged and sexually active women (2,3), the population at highest risk of unintended pregnancies (4). In comparison, the control group includes such medications as propranolol and theophylline, which are used for treatment of cardiac and respiratory conditions more common among older women (5,6), wi...

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  • Is this evidence enough to change our medical advice to coffee-consumer pregnant mothers?

    In my daily practice that is limited, I've been allowing my patients to drink two cups of coffee a day, although they tend to be restrictive when applying my advice. Most of them are healthy women in their 30s. Whenever they've had a bad result, it has been attributed to other causes. When reading your impeccable research work, I've missed some comment on the clinical relevance of certain outcomes as a minor change in birth weight; moreover, aging or prior medical history may act as confounders of negative pregnancy outcomes. I appreciate your effort very much, but I consider the change of medical recommendations requires a more in-depth assessment, by means of one or more randomized clinical trials. Let's bear in mind than in my home country, Spain, temperatures in summer may be unbearable if you are an active working mother-to-be. And, definitely, our medical role is to give evidence-based solutions and avoid changing our pieces of advice every couple of years.

  • Bias in reporting

    ‘There is no safe level of caffeine intake in pregnancy’. That is the conclusion of this ‘narrative review’ of caffeine safety in pregnancy (BMJ Evidence Based Medicine, Open Access) which a patient brought to my attention very recently after hearing about it on the mainstream media. I felt that it requires clarification to avoid concern amongst the general public and those unable to analyse and critically appraise the literature.

    The single author concluded that, after finding 48 studies (37 observational studies and 11 meta-analyses), caffeine intake in pregnancy significantly increases the risk of miscarriage, stillbirth, low birth weight, childhood leukaemia and childhood overweight/obesity. The author then goes on to recommend that all worldwide guidelines (including American, UK and Australian) stating the safety of caffeine in doses<200mg/day (approximately 2 cups of coffee) should be revised to say ‘there is no safe level of caffeine in pregnancy’.

    However, there is no need to panic, which appears to be the response of the mainstream media and patients from the general population. Very soon after publication, this paper was picked up by several news outlets including CNN, The Guardian and also on a number of social media streams. Women were being told not to drink coffee in pregnancy the same way they were being told not to drink alochol.

    This paper is far from as conclusive as it tries to make the reader believe, but serves as a good exampl...

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  • Insufficiently Robust Methodology and risk of bias

    Editor,
    I welcome this publication with it's focus on a potentially important cause of adverse pregnancy outcomes.
    This study has several methodological faults that need to be declared and addressed.
    The study's single author has written extensively on this topic over the last 29 years. He cites several of his own publications in the paper, As far as I can judge, they are all critical of caffeine in pregnancy. Surely this puts him at risk of bias.
    The best way to address such bias is to conduct a systematic review with precise methodology. Also, at least one other author should be involved in assessing suitability of the papers, and minimising bias.
    Only English language papers are studied.
    Only PubMed and Google Scholar are searched. No reference is made to other important databases such as CDSR, Medline, EMBASE and CINAHL.. There does not appear to have been any pre-specified eligibility criteria in assessing whether or not studies should be included in the review e.g. community based populations or pre defined study methods.
    There is no attempt made to assess the quality of the studies used in writing the paper.
    The search strategy appears vague.
    The results in table 1 give odds ratio but there is no quantification of this. What we need is absolute risk with numbers needed to harm. If this figure cannot be calculated then we should be told and given the reasons why.

    These limitations need to be ackno...

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  • Frustrated coup to the LDL role in atherosclerosis paradigm

    In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
    In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...

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  • Frustrated coup to the LDL role in atherosclerosis paradigm

    In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
    In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...

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  • Honey and in vitro antibacterial properties including Helicobacter pylori

    I read with interest the latest evidence for honey and treatment of coughs which was also reported widely in the national press (1). Honey has been shown in laboratory in vitro studies to inhibit bacterial growth including Helicobacter pylori linked with dyspepsia and gastritis (2, 3). Concentrations between 10-20% honey has been shown to be effective against both Gram negative and Gram positive bacteria (3). My late father Professor MNH Chowdhury, a clinical bacteriologist, researched this in the 1990s and advocated Manuka honey especially for its healing and antibacterIal properties. Interestingly, the in vitro findings showed some isolates were resistant to various antimicrobial agents but honey inhibited these organisms also (3). Secondary bacterial infections may respond to this simple remedy after primary viral coughs and colds and need further clinical study.
    References
    1. Abuelgasim H, Albury C, Lee J. Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis. BMJ Evidence Based Med 2020, 18 Aug online; bmjebm-2020-111336.
    2. Rashed RS, Ayoola EA, Mofleh IA, Chowdhury MNH, Mahmood K, Faleh FZ. Helicobacter pylori and dyspepsia in an Arab population. Trop Geogr Med 1992; 44(4), 304-7.
    3. Ali AT, Chowdhury MNH, al Humayyad MS. Inhibitory effect of natural honey on Helicobacter pylori. Trop Gastroenterol 1991; 12(3), 139-43.

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