102 e-Letters

  • Burden of proof or disproof?

    In a systematic review of cholesterol reduction clinical trials, DuBroff et al claimed that “the evidence presented challenges cardiovascular disease prevention through targeted reductions of LDL-cholesterol”. However, it should be noted that the concept authors claim to challenge has never been proved, nor properly tested (1). This raises the question of whether there is a need to disprove an unproven concept. In science, the burden is on the proof.

    Nevertheless, if it was to disprove, we must recognize the limitations of the present study. Regarding testing "the target paradigm", the authors first categorized the trials as to whether they did or did not meet average LDL-cholesterol reduction recommended by AHA/ACC 2018 guidelines (2) for individuals. Then, they intended to test the association between reaching this arbitrary target (suggested by one specific guideline) with the trial being positive or negative regarding death or cardiovascular events. However, no statistical inference was performed for this main analysis and no significance level was presented for the interaction between reaching the target and having clinical benefit. Instead, in this systematic review that intended to test a hypothesis that implied interaction phenomenon, the authors "intentionally did not perform a meta-analysis" under the justification that trials “involved three different drug classes”.

    Finally, as the authors noted, it was a systematic review of s...

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  • Setting the Record Straight on Saturated Fat and LDL-cholesterol. Ignorance is not bliss.

    Like so many purported pundits, DuBroff R, de Lorgeril M [1] have attempted to dispute the significance of the role of saturated fat (triglycerides) and LDL-cholesterol in the development of coronary artery disease, while noting the importance of inflammation itself [1,2]. In law, ignorance of the law is not a defense - the same is true for medicine. Not understanding something does not make you an expert [2] and it does not make your argument valid. Appealing to the court of public opinion does not make it so either. Accordingly, we present a brief explanation of why the authors [1,2] – and others – have presented an invalid discussion of the role fat and LDL-cholesterol plays in coronary artery disease.

    In the mid-1990s, as one of the reviewers for the American Heart Association, the first author of this letter, Dr Richard M Fleming (RMF) introduced a then controversial theory stating that Coronary Artery Disease (CAD) is the result of an inflammatory process, which builds up within the walls of the arteries impairing their ability to dilate and increase coronary blood flow when needed; thus producing regional blood flow differences resulting in angina [3-6] and ultimately myocardial infarction (MI) and death.

    In recent years, people promoting various dietary and lifestyle practices – particularly those promoting LowCarb-Keto diets, have used the obesity epidemic to focus attention on obesity and weight loss. These same individuals have not demonstrated th...

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  • UK TIME study will also provide further evidence

    Thank you for this measured summary of the recently published HYGIA trial. I am pleased to see you mention the BedMed study ongoing. Readers may be interested to know that there is another study, already in follow-up, which will provide further evidence on whether night-time dosing of blood pressure medications really is better in the prevention of cardiovascular events and mortality.

    The University of Dundee's Treatment in Morning vs Evening (TIME, www.timestudy.co.uk) study, funded by the British Heart Foundation, aims to answer the same research question. TIME has recruited 21,104 participants across the UK and should finish in the first half of 2020.

  • Considerations for future age-based risk reviews

    I read this rapid review with interest and agree this topic has reached a point at which a full systematic review could be useful. I have a few suggestions to the authors and/or future reviewers in this area, as there are several nuances in the studies presented that have not been acknowledged.

    Future reviews need to consider what primary outcome the study was powered for, and what the comparator is. For example, Bonner et al. looked at physical activity and diet changes as well as smoking in a combined measure and found no statistical difference between absolute risk and heart age when presented in the same format, but the smoking result is isolated and reported as “clinically significant” in the review. In contrast, Lopez-Gonzalez et al. compared an interactive online format for heart age to usual care which generally involves a verbal description of absolute risk by the doctor, so it is difficult to determine whether heart age or a more engaging presentation format produced the results.

    Psychological outcomes should also be considered. Modest gains in behaviour change may not be outweighed by reduced accuracy of risk perception, negative affect or reduced credibility of the assessment as per Bonner et al. While these age-based formats appear to elicit a stronger emotional response, this may not be sufficient to produce greater behaviour change or even intentions without additional support (e.g. Soureti et al. and Witteman et al.). It is unclear from the r...

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  • Response: Research Integrity & BJPsych

    Dear Editors,

    We thank Dr. Bhui and Mrs. Shuttleworth for commenting on our paper and giving us the opportunity to clarify some aspects of our methods. In their response, they invite us to elaborate on our rationale for journal selection and if we infer that spin is more prevalent in psychiatry journals versus psychology journals. Here, we attempt to clarify our methodology and conclusion regarding our article over spin.

    The journals in our study were selected due to their ranking on Google Scholar Metrics under the subcategory “Psychiatry” at the time of the search [1]. It should be noted that as this search was conducted on May 21 2018, the rankings found today may differ from what we found. We selected the highest 10 ranking journals on Google Scholar, according to their h-5 index. However, not all journals primarily published RCTs in humans and were therefore excluded from our study, leaving us with a total of 6 journals.

    The aim of our paper was not to compare the prevalence of spin between trials published in psychiatry and those published in psychology journals. Rather, our study examined the rates of spin in RCTs published in high-ranking journals, as indexed by a popular journal ranking platform.

    We commend the editors of British Journal of Psychiatry on taking steps to confront spin, such as mandatory use of the CONSORT checklist. For example, CONSORT item 22 requires that interpretations presented in discussion sections of clinical t...

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  • A shot of light in the dark, but still waiting for the big bang

    I commend the authors for their well balanced and informative review on recent evidence on reduced fetal movement (RFM). Over the years I sadly saw the practice in the NHS being driven by fear and emotions rather than evidence, certainly, some units now offer mothers induction of labour even after a single episode of RFM! Junior doctors are prompted to act on RFM at induction day, and hospitals are adopting the official Care Bundle from the NHS promoting action (http://www.geh.nhs.uk/latest-news/saving-babies-lives-campaign/) yet, where is the evidence that any of this is beneficial?! certainly efforts like the AFFIRM study need wider dissemination and adoption by policymakers. The question remains, what can we offer to worried couples presenting with RFM daily? Still waiting for the game-changer.

  • Industry sponsorship bias in the SGLT2 inhibitor study

    The EBM Verdict by O'Sullivan on the CREDENCE trial of canagliflozin and renal outcomes (1) concluded that "Sodium-glucose cotransporter-2 (SGLT2) inhibitors appear effective to reduce cardiovascular events and deterioration of renal disease in patients with type 2 diabetes and renal impairment." O'Sullivan stated that the study was well-conducted based on conventional assessments of validity (blinding, randomization method, choice of outcomes). However, an important overlooked source of potential bias was not mentioned. The CREDENCE study was sponsored by the pharmaceutical company (Janssen). The analyses of the data was conducted by Janssen, and important conflicts of interest were reported by authors of the paper. A Cochrane review of the relationship of industry sponsorship and research results (2) found significantly more favorable efficacy results in studies by the manufacturing company than sponsorship by other sources, and that the industry bias could not be explained by other "risk of bias" assessments. This important source of bias warrants caution in the interpretation of the results in the absence of independent (non-industry sponsored) data.

    1. Perkovic V. et. al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. CREDENCE Trial Investigators. N Engl J Med 2019;380:2295–2306.
    2. Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systema...

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  • An epidemic of spin in psychiatry

    Psychiatry is, to an extent, a looking glass world, in which the evidence base can be shrunk, expanded, or, the same as Alice, made to descend down a deep, deep hole.

    Joanna Moncrieff for anti- psychotics (1), and Irving Kirsch for anti- depressants, have been suspicious that the drugs concerned may often be not much better than placebo- or that the complexity of the drugs makes comparison with placebo problematic. (Moncrieff cites the impossibility of true double blinding because side effects are, unfortunately, so evident for patients and clinicians alike).

    The problem is money. Big Pharma tends to be avaricious, and how soon greed may make one disregard that silly obstacle known as truth!

    Spin can be the case even if there appears to be statistical significance. A large sample size- as in meta-analysis- will conclude a tiny difference, of no medical worth, is statistically significant. 'Overpowering' is spin too.

    Big Pharma, roaming around its own psychopharmacological 'wonderland', is ensuring, in the most bizarre and baffling ways possible, that everything is 'curiouser and curiouser'.


    (1) The Bitterest Pills. The Troubling Story of Anti-Psychotics. Joanna Moncrieff. Palgrave Macmillan. 2013.

  • The utility of Medicines Information services in addressing GPs' specific information needs

    Muscat et al1 report on their evidence-based information or ‘literature searching’ service supporting clinicians to answer their clinical questions. They found that treatment-related enquiries were one of the most common categories of clinical questions from a group of General Practitioners (GPs) from five practices in NSW and QLD, Australia. Medications are included in the classification systems used by the group. In particular the taxonomy of generic clinical questions includes at least seven codes specifically incorporating drug-related issues such as timing (code, indications (code* and, safety (code, adverse drug reactions (codes and and drug interactions (code
    Medicines Information (MI) services also support clinicians in providing effective patient care and optimising therapeutic strategies in a timely manner. The National Prescribing Service funded Therapeutic Advice and Information Service (TAIS) operated in Australia from 2000 to 20102. It was a telephone-based service provided by a consortium of hospital-based medicines information services and handled over 6 000 enquiries annually from community based healthcare professionals across Australia. One third of enquiries were from GPs. Requests for advice regarding medication safety issues such as adverse drug reactions, drug interactions, dosing or administration and pregnancy or lactation were among the most common, supporting the findings of Musc...

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  • Research Integrity & BJPsych

    Dear Editor,

    We welcome the publication of the Jellinson study (9) which is consistent with the focus on research integrity lead by the BJPsych editorial team (please see our most recent retraction (1) and associated editorial (2)).

    The issue of ‘spin’ is a widespread problem across the whole research community and is not unique to psychiatry as recognised by the authors of this study (3, 4, 5). We note that according to the protocol the authors are carrying out and publishing similar studies in the fields of cardiology, otolaryngology (6), orthopaedic surgery, obesity medicine (7), anaesthesiology (8) and emergency medicine.

    It is unclear from the article or protocol why this subset of journals was chosen for evaluation. We would be interested to know why the number of journals was limited to 6 and what were the parameters for a journal to be considered ‘influential’. It is also interesting to note that none of the journals chosen exclusively publish psychology research (2 publish psychiatry and psychology research and the remaining 4 journals solely publish psychiatric research). Do the authors infer that the problem is more prevalent in influential psychiatry journals? The authors also acknowledge that identifying spin is subjective, highlighting the difficulties faced by journal editors and reviewers who are also trying to identify instances of spin.

    Since December 2017 (the end of data extraction in the study), the BJPsych has proactively t...

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