25 e-Letters

  • Providing comments on methods, analyses & conclusions. Seeking additional information & response from the authors.

    I read with interest the Nordic myocarditis cohort study by Husby et al (1) on clinical outcomes of three different types of myocarditis: COVID-19 mRNA vaccination-associated (“vaccine-associated”), COVID-19 infection-associated (“infection-associated”) and “conventional” myocarditis. I would like to make several comments and request response from the authors.

    A significant limitation of the Nordic and other similar studies is the under-diagnosis of COVID-19 vaccine-associated myocarditis and possibly COVID-19 infection-associated myocarditis. To be included in the Nordic myocarditis cohort study, an individual had to develop symptom(s) with myocarditis, present to a medical provider with such symptom(s), and the medical provider had to consider myocarditis and then order at least ECG or cardiac enzyme(s), and the individual had to be admitted to the hospital as an inpatient. Individuals with myocarditis who did not satisfy all the above conditions would not have been included in the Nordic study. Only a prospective study with continuous screening for myocardial injury/inflammation would be able to provide complete information on the incidence and outcomes of myocarditis associated with COVID-19 vaccine or infection. Limited prospective data on myocardial injury post-vaccine is currently available, suggesting significantly more common occurrence (2,3) than proclaimed but with unknown long-term prognosis.

    During the COVID-19 pandemic, there were many more pat...

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  • Seeking more information on risk factors and vaccination status of those w/myocarditis post-SARS-CoV-2

    To the Editor:

    We read with interest the Nordic registry study by Husby et al on clinical outcomes of three different types of myocarditis: SARS-CoV-2 mRNA vaccination-associated, COVID-19 associated and “conventional” myocarditis. We appreciate the information the authors provided on patient characteristics by myocarditis type. We note >50% patients with COVID-19-associated and conventional myocarditis were over 40, those with vaccine-associated myocarditis were younger on average and 38% were 12-24 years v.s <25% for the other two types. Further, the proportion of men was higher in all three categories, and the proportion of patients with underlying comorbidities similar; however, we wonder, given the relatively small number of patients, if the authors could disclose which comorbidities and how many were present (in total) among the patients with COVID-19 vs. vaccination-associated myocarditis, perhaps as a summary table.

    Second, do the authors have any information on the vaccination status (number of doses and dates given in relation to the myocarditis diagnosis) among those categorized as having COVID-associated myocarditis? If so, could this information be broken down by age group?
    Related, the most recent exposure defined the type of myocarditis in patients who received both an mRNA vaccine and had a positive test for SARS-CoV-2 in the last 28 days. We therefore wonder if the authors could provide the number of times both were diagnosed with...

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  • Associatoin between coeliac nad cardiovascular diseases ?

    Dr Conroy and colleagues investigated 469,095 adults aged 40-69, to find 40687 incident events (9 per 1000 person years) of cardiovascular disease in 2083 coeliac sufferers giving a hazard ration of 1.27 (1.11- 1.45) (1). What are the mechanisms for these clinical associations ?

    The pathophysiological mechanism in DP Burkitt”s “high fibre” hypothesis to explain chronic diseases is autonomic injury caused by straining on the toilet (2, 3). Coordinated straining may injure branches of sympathetic segments T10-L2 with the potential to injure pelvic organs including kidneys and adrenals. These may extend to contiguous segments at T8-9r supplying small bowel (cf nulliparous endometriosis, inflammatory bowel disease and hypertension). In DP Barkers “fetal origins of adult diseases” hypothesis the pathophysiological mechanism is an in utero injury to autonomic vasomotor nerves in small babies caused by involuntary “fetal hypertension” (4, 5). Kidneys and pancreas seem to bear the brunt of this assault that may result in type 1 diabetes mellitus and hypertension in later life.

    On this simple analysis there are, therefore, potential primary neurological mechanisms to account for both cardiovascular and autoimmune diseases within these data-driven hypotheses for chronic diseases. Are autoantibodies secondary consequences of primary denervatory injuries in these chronic “autoimmune” conditions ?. If the BioBank held details of birthweights or bowel habits (...

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  • Are not umbrealla reviews the same as overviews of reviews?

    We read with great interest the article on ‘Conducting umbrella reviews’. In our view, it is important to highlight that what is described as ‘umbrella reviews’ in this article is often referred to as ‘overviews (of reviews)’, and shares similar definitions and goals, namely to synthesise evidence at the systematic review-level. The term ‘overviews of reviews’ is employed by Cochrane, a leading international organization for evidence synthesis. The corresponding chapter in the Cochrane handbook (1) was revised a few years ago and provides a summary of methods research for this type of evidence synthesis along with recommendations for conducting overviews of reviews. Although this has been prepared for Cochrane, we think that the vast majority of the content can also be used outside Cochrane and for a range of research questions. It provides guidance for topics not mentioned in your article such as dealing with overlapping primary studies across reviews on the same topic, decision tools supporting the inclusion of reviews, and updating reviews by conducting supplemental searches for primary studies. Most importantly, in the article by Belbasis et al. there is no explicit mention of assessing the quality or risk of bias of the included reviews and there is no mention of the recently published reporting guideline for overviews of reviews of healthcare interventions (2).

    A large body of research by many evidence synthesis groups over the past 10+ years exists to advan...

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  • External valdiation of QFracture-2012

    As authors of the QFracture papers1-3, we read this article by Livingstone et al with interest. They stated that the had externally validated the QFracture-2016 algorithm using CPRD4. The authors report that whilst there was very good to excellent discrimination, calibration was poor. The authors attributed an apparent under-prediction to their outcome definition using the CPRD validation dataset since this included GP data linked to hospital data. However, we think this under-prediction is due to the authors using the wrong algorithm – the authors have confirmed that they had used a previous version (QFracture-2012) which is based on unlinked data. The QFracture-2016 algorithm is the version which is currently recommended and used in the NHS and is derived from the QResearch database including GP data linked to hospital and mortality data3. Therefore, the authors need to correct their paper and update their conclusions accordingly. We would also like to highlight that the code groups for QFracture are available here https://www.qresearch.org/data/qcode-group-library/
    1. Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: Prospective derivation and validation of QFractureScores. BMJ (Online) 2009;339(7733):1291-95. doi: 10.1136/bmj.b4229
    2. Hippisley-Cox J, Coupland C. Derivation and validation of updated QFracture algorith...

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