1238 e-Letters

  • If not overdiagnosis, what are these excess cancers?

    Chaltiel and Hill show that studies based on individual data indicate a low percentage of overdiagnosis from mammography screening. How to explain the vast excess of cancers that is consistently associated to mammography screening in observations on aggregated data? We have shown that this excess occur after more than 5 years after mammography, in every country, and can only be interpreted as originating from radiation-induced cancers (1,2).
    The absence of discussion on this issue is worrying, because Catherine Hill is perfectly aware that I have been dismissed from my permanent position at the INSERM after alerting on these mammography-induced cancers.

    1) Corcos D. Breast cancer incidence as a function of the number of previous mammograms: analysis of the NHS screening programme. BioRxiv 2017. doi: https://doi.org/10.1101/238527 .
    2) Corcos D & Bleyer A. Epidemiologic Signatures in Cancer. New Engl J Med. 2020. 382(1):96. doi: 10.1056/NEJMc1914747

  • When talking about evidence on overdiagnosis, complexity is not a substitute for quality

    When the Independent UK Panel, led by Sir Michael Marmot, estimated breast cancer overdiagnosis they used the gold standard - randomised trials with long follow-up without screening in the control group. The Panel chose not to use the observational studies because “this method could give no reliable estimate of the extent of overdiagnosis.”(1) Inherent biases in observational studies are also the reason that the UK National Screening Committee requires high-quality, randomised trial evidence on benefits and harm before screening is introduced.(2)

    Conversely, Chaltiel and Hill (3) dismiss the gold standard estimates of overdiagnosis and focus on an observational study (4) while they reject the estimates from another observational study (5) that agrees more closely with those of the randomized trials. Notably the estimates from the trials were consistent with each other. Chaltiel and Hill’s choice conflicts with the fundamental principles of evidence-based medicine.

    An impartial assessment of the risk of bias of all observational studies of breast cancer overdiagnosis found that many studies, including ones using individual data, were at high risk of bias because of selection bias, confounding, inadequate adjustment for lead time and non-transparent methods.(6) It is misleadingly simplistic to assert that having individual level data provides protection against significant bias, as we explain below.

    Chaltiel and Hill’s study design of choice is an...

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  • Author response to Prof. Kawada

    We thank Professor Kawada for the interest in our paper. We very much agree with the points raised.

    The material of the present study (1) consists of men who had served in managerial positions in the fields of industry and commerce, or as entrepreneurs. They provided self-assessed stressfulness ratings of their entire work careers. The findings showed protective effects of less stress on decreased risk of pre-frailty relative to non-frailty. While we are aware that this does not replace information on psychosocial working conditions, it may help us understand that both circumstances during the working career and retirement jointly contribute to the health of retirees. Kalousova et al. found this particularly true in the baseline category ‘low reward’ of psychosocial working conditions (2). Also a disadvantaged group, as Professor Kawada shows, were manual workers, who were at increased risk of adverse employment outcomes relative to other occupational groups (3). This is important policy-wise, and though the present study included a more homogenous group representing higher occupational and socioeconomic groups, it shows that even in such groups differences in frailty may stem from factors around the working career and retirement. Relevant to this group of men with managerial/professional occupational backgrounds, Schütte et al. found that both low job promotion and high insecurity at work contributed to poorer psychological well-being in a study capturing 34 Europe...

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  • Development of a core outcome set for congenital pulmonary airway malformations

    We highly appreciate that Hall and colleagues have critically reviewed our protocol and acknowledge their concerns regarding the lack patient and public involvement (PPI). We are aware of the COS-STAD recommendations and have carefully considered PPI. Nevertheless, we ultimately decided not to include parental input in the Delphi process. The most important consideration was that parents of asymptomatic patients may have difficulty providing input on desired outcome measures, since most of them are not confronted with symptoms or complications. Furthermore, to the best of our knowledge, patient societies or support groups for CPAM patients are scarce and widespread. This makes it difficult to establish an unbiased general opinion on the most important outcome parameters for this patient-group. Moreover, gathering a well-balanced and unbiased patient panel could prove to take a considerable amount of time. We would rather put this time to use in the development of clinical trials, since currently no prospective outcome studies have been published yet. Having said this, we intend to incorporate PPI in the development of clinical studies, thus including their essential input in the study design. We believe we have adequately addressed the concerns of our colleagues, and trust we can count on them for future collaboration in the field of congenital lung disease.

  • Response to Dr. Pedro Santos-Moreno

    We thank Dr. Pedro Santos-Moreno for his interest in our article. Dr Santos-Moreno highlights that PANLAR (the Panamerican League of Associations of Rheumatology) has been working toward ways to overcome challenges in lack of access to specialist care and treatments as well as the fragmentation of health care. Given the diverse healthcare settings in Latin American and the Caribbean, Dr Santos-Moreno and colleagues conducted a consensus exercise to develop recommendations for improving quality of care 1. They have developed a concept of a “Center of Excellence in RA”. Importantly, they define different standard requirements for centers including: a minim “standard”, “optimal” and “model” center of excellence 1. To further these efforts, they have described an implementation plan for the centers 2 as well as an approach to accreditation 3. We congratulate Dr. Santos-Moreno and colleagues on these important efforts. Their work is highly complementary to our work in Canada to develop a framework for quality measurement in rheumatoid arthritis 4-6.

    We agree with the comment by Dr. Santos-Moreno that a minimum standard of care for RA should be defined, although we note that the application of performance measures to capture this may depend upon many factors including data availability, accreditation standards, and physician pay for performance programs. In the development of our quality framework for RA we recognized that for some health systems data may not be availabl...

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  • More evidence that high LDL-cholesterol is beneficial

    That the mortality of patients with cardiogenic shock is inversely associated with low-density-lipoprotein cholesterol (LDL-C), as documented by Jin et al.1 is in accordance with our reviews of 38 studies, where the authors had followed more than six million people of all ages for several years after having measured their LDL-C.2,3 In almost all of the studies those with high LDL-C lived just as long or longer than those with normal or low LDL-C. These findings are of course most surprising because according to the official guidelines, high LDL-C is an important risk factor for cardiovascular disease (CVD), the commonest cause of death in most countries.

    However, many other contradictory observations have been ignored by the guideline authors as well.4,5 For example, people with low cholesterol become just as atherosclerotic as people with high cholesterol;5 LDL-C of patients with acute myocardial infarction is lower than normal and if it is lowered even more, their risk of dying prematurely increases.5 Furthermore, there is no exposure-response in the statin trials.5

    Familial hypercholesterolemia (FH) is seen as a strong argument for the view that high cholesterol is the main cause of CVD, although multiple studies are contradictive.6 For instance, three large follow-up studies of people with FH have found that on average, they lived just as long or longer than other people.6 The few who suffer prematurely from CVD have inherited increased levels of vario...

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  • Magnesium and clearing statin myalgias

    While it is a clinical insight subject to multiple variables, I have consistently been able to clear up statin myalgias an have the patient remain on the statin by having the patient take enough of an absorbable magnesium (usually a chelated magneium) to achieve a blood level of magnesium of 2.2 mg/dL or only slightly higher plus have loose stools. After the myalgias have cleared with this treatment, the magnesium dose can be reduced so the stools are no longer loose but the blood levels remains 2.1-2.4 ng/dL

  • RE: Letter to the Author

    A medical student perspective on history-taking for a child presenting with a limp: doing it for the first time

    Ravi Patel & Matthew Knights

    A child presenting with a limp, is a common presentation in primary and secondary care in the UK. It can be due to a number of different aetiologies with varying degrees of severity. A concise history offers the opportunity to identify key risk factors, mechanisms of injury, duration of symptoms and a collateral history from family members, thus is an important skill for all healthcare professionals irrespective of speciality. [1,2] However, many medical students and newly graduated junior doctors feel-ill prepared to take one. [3] Missing key red-flags, delaying diagnosis and referral for appropriate management. We present our own experiences of history taking and discuss how improvements can be made within the medical school curriculum.

    Key factors in making history taking a challenge for children presenting with a limp for medical students or clinicians include; quantifying duration and pain the child is experiencing, the precise location of pain, establishing the true mechanism of injury, weather a non-accidental injury is questionable, cultural differences when taking a collateral history and the birth and developmental history. This applies even more so to those with inadequate training. A recent survey conducted by the University of Newcastle medical school found average duration of the T&O attachm...

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  • Response to Pedersen's comment to our paper "Routine induction in late-term pregnancies: follow-up of a Danish induction of labour paradigm

    We appreciate the interest that Dr. Pedersen has shown in our paper, but he has apparently misunderstood some aspects of our analysis. In the analysis of the stillbirth data, we first described the dependence of log (rate) on calendar year by a straight line. Next, we allowed the slope to change from 2011 onwards (a so-called linear spline with a knot at 2011). This did not improve the fit significantly. This is the analysis reported in our paper. Besides we also tried to see if a change in intercept from 2011 onwards would lead to a significantly better fit. This was not the case. This latter model is the one that Dr. Pedersen considers, but this was not the one presented in our paper.

    We are also concerned about Dr. Pedersen’s suggestion that we have been unresponsive to his questions. We can document at least 11 email correspondences and two face to face meetings with Dr. Pedersen to accommodate Dr. Pedersen’s wish for more information and discussion of our analyses. These mails and meetings have also included the Lead Professor of Dr. Pedersen’s department and a Professor in Biostatistics from Aarhus University. The Professor in Biostatistics has confirmed to all included in the meetings and in the additional emails that our analysis as well as our conclusions in the paper were valid.

    Eva Rydahl, Eugene Declercq, Mette Juhl, Rikke Damkjær Maimburg

  • RE: Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course

    De Rubeis et al. conducted a systematic review to evaluate the effect of disasters, including pandemics, on cardiometabolic outcomes (1). Clinical outcomes were checked ≥1 month following the disaster. The effects of exposure to disaster during pregnancy/childhood and during adulthood were included, and increased cardiovascular disease incidence or mortality, diabetes and obesity were observed in each study. Although the biological mechanisms of the association might be complex, long-term effects of disasters on cardiometabolic health should be explored to elucidate prevention strategies against forthcoming disasters (2-4).

    1. e Rubeis V, Lee J, Anwer MS, et al. Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: a systematic review. BMJ Open. 2021;11(5):e047152.
    2. Chua MWJ. Managing patients with obesity in the post COVID-19 world: Time to sharpen the saw. Obes Res Clin Pract. 2021;15:85-88.
    3. Narita K, Hoshide S, Tsoi K, et al. Disaster hypertension and cardiovascular events in disaster and COVID-19 pandemic. J Clin Hypertens (Greenwich). 2021 ;23(3):575-583.
    4. Burg MM, Soufer R. Post-traumatic Stress Disorder and Cardiovascular Disease. Curr Cardiol Rep. 2016;18(10):94