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 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...
Chaltiel and Hill’s study design of choice is an age-period-cohort (APC) analysis, a notably complex design that relies on a strong statistical assumption of distinct, independent, and separable effects of the three core variables in APC analyses, resulting in the well-recognized “identifiability problem” of the method.(7) They also superimpose the additional variable of geographic variation. As the authors state, “there was no obvious control population allowing direct estimation of overdiagnosis” so they generate expected breast cancer incidence in a pseudo-control population from a model that attempts to simultaneously accommodate screening invitation, period, region, and generation, along with interactions between period and generation (footnote to their Table 1). The footnote only hints at the inherent complexities. The number of cases in the absence of screening is obviously critical to the resulting calculation of overdiagnosis; and there are a lot of moving parts in the proposed model, each with its unknown degree of uncertainty. The estimated number of expected cases in Table 1 is therefore a form of pseudo-precision, and it would be a mistake to equate this complexity with accuracy. Further uncertainty comes from low numbers – the population of Funen women aged 50 to 69 years was about 50,000 and Njor et al included less than half of these women (those aged 59 to 70 years), ending up with an ‘intervention group’ much smaller than those groups which informed the estimates by Marmot, and that used by Jørgensen et al. who included all women aged 50 to 69 years in all Danish regions that offered screening (about 100,000 women). By excluding women in their 50’s, Njor’s analysis also excluded many of the crucial first (prevalence) screening rounds where overdiagnosis is likely most pronounced, and as such their results do not fully represent the target population in national breast cancer screening programmes.
The UK Panel presented four ways of calculating percentage estimates of overdiagnosis and preferred two of them, which they presented in a meta-analysis: 10.7% of all breast cancers diagnosed during active screening years plus the rest of the screened women’s lives, and 19.0% of all breast cancers diagnosed during the years of active participation in screening. There is no “right” percentage - each addresses a different question. Yet Chaltiel and Hill present all percentage estimates (e.g. in their Figure 1) as if they were directly comparable. They are not and the estimates from Njor et al and Jørgensen et al. cannot be directly compared as they used different denominators. Presenting percentages that are not comparable as if they were perpetuates the confusion and disagreement that exists over breast cancer diagnosis estimates, and should be avoided.
Lastly, Chaltiel and Hill took the article of Spix et al as an example for overestimation of overdiagnosis. However, overdiagnosis only slightly reduced from 71% to 62% after correction for neuroblastoma found after the screening period.(8) More important, the data used by Spix et al imply fewer neuroblastomas than expected (i.e., if screening had not existed) when children are older and no longer screened. However, Danish data showed no observable compensatory drop among women previously screened as they aged past 70, in the years following the period in which they had been screened. Jørgensen et al performed extensive analyses to look for such a deficit at the end of a long observation period when all women over 70 years would have been offered screening previously. There was no such decline.(9) Similar observations have been made in countries like Sweden and the Netherlands; in these two countries after thirty years of high participation to breast screening, breast cancer incidence rates have not declined among older women no longer invited to screening.(10) (11) .
Comparing incidence trends in breast screening with those of other cancer screening programmes is informative. Ovarian cancer screening likely causes little overdiagnosis and its effect on incidence differs markedly from that of breast screening.(12) Likewise, cervix screening and colorectal cancer screening can cause declines in incidence of invasive cancers due to removal of precursors, albeit at the cost of very large increases in non-invasive intra epithelial lesions, many of which regress spontaneously. In contrast, although about 20-25% of cases detected with breast screening are DCIS, incidence of invasive breast cancer continues to increase, even after decades of screening. Breast cancer screening affects incidence rates in ways that carry all the hallmarks of substantial overdiagnosis.(13)
1. Marmot MG, Altman DG, Cameron DA et al. The benefits and harms of breast cancer screening: an independent review. British Journal of Cancer. 2013;108(11):2205-40.
2. National Screening Committee. Criteria for appraising the viability, effectiveness and appropriateness of a screening programme. 2015.
https://www.gov.uk/government/publications/evidence-review-criteria-nati... Accessed 9 July 2021.
3. Chaltiel D, Hill C. Estimations of overdiagnosis in breast cancer screening vary between 0% and over 50%: why? BMJ Open. 2021;11(6):e046353.
4. Njor SH, Olsen AH, Blichert-Toft M, Schwartz W, Vejborg I, Lynge E. Overdiagnosis in screening mammography in Denmark: population based cohort study. BMJ : British Medical Journal. 2013;346:f1064.
5. Jørgensen KJ, Zahl P-H, Gøtzsche PC. Overdiagnosis in organised mammography screening in Denmark. A comparative study. BMC Women's Health. 2009;9(1):36.
6. Carter JL, Coletti RJ, Harris RP. Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ : British Medical Journal. 2015;350:g7773.
7. Browning MC, Ian; Knoef, Marike. The age-period cohort problem: Set identification and point identification. 2012.
8. Spix C, Michaelis J, Berthold F, Erttmann R, Sander J, Schilling FH. Lead-time and overdiagnosis estimation in neuroblastoma screening. Stat Med. 2003;22(18):2877-92.
9. Jørgensen KJ GP, Kalager M , et al . Breast cancer screening in Denmark: a cohort study of tumor size and overdiagnosis. Annals of Internal Medicine 2017;166:313-23.
10. The NORDCAN project https://www-dep.iarc.fr/NORDCAN/english/frame.asp. Accessed 9 July 2021.
11. Autier P, Boniol, M., Koechlin, A., Pizot, C. Boniol, M. Mammography screening effectiveness and overdiagnosis in the Netherlands: population based study. BMJ 2017;359:j5224
12. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387(10022):945-56.
13. Welch HG, Kramer BS, Black WC. Epidemiologic Signatures in Cancer. New England Journal of Medicine. 2019;381(14):1378-86.
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...
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 European countries (4). It is therefore possible that different working conditions may affect the health outcomes of different occupational groups, a field of further study for occupational cohorts.
1. Haapanen MJ, Von Bonsdorff MB, Perttilä NM, et al. Retirement age and type as predictors of frailty: a retrospective cohort study of older businessmen. BMJ Open. 2020;10(12):37722. doi:10.1136/bmjopen-2020-037722.
2. Kalousova L, de Leon CM. Increase in frailty of older workers and retirees predicted by negative psychosocial working conditionson the job. Soc Sci Med. 2015;124:275-283. doi:10.1016/j.socscimed.2014.11.055.
3. Palmer KT, D’Angelo S, Harris EC, et al. Frailty, prefrailty and employment outcomes in Health and Employment after Fifty (HEAF) Study. Occup Environ Med. 2017;74(7):476-482. doi:10.1136/oemed-2016-104103.
4. Schütte S, Chastang J-F, Malard L, Parent-Thirion A, Vermeylen G, Niedhammer I. Psychosocial working conditions and psychological well-being among employees in 34 European countries. Int Arch Occup Environ Heal 2014 878. 2014;87(8):897-907. doi:10.1007/S00420-014-0930-0.
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.
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...
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 available to measure all performance measures included or available resources to support ongoing measurement and quality improvement efforts 5. We proposed that interested sites could consider initially adopting a smaller set of measures for local testing and implementation as appropriate to their specific contexts 5. We did not however define a “minimum set of measures”, and this is an interesting concept we will reflect upon further. In our own local context, a measurement priority for physicians was on “treating to target” and we selected a limited number of measures to evaluate treat to target processes and patient outcomes, which has been a valuable exercise 4. We would welcome further discussion and collaboration internationally on this important topic.
1. Santos-Moreno P, Galarza-Maldonado C, Caballero-Uribe CV, et al. REAL-PANLAR Project for the Implementation and Accreditation of Centers of Excellence in Rheumatoid Arthritis Throughout Latin America: A Consensus Position Paper From REAL-PANLAR Group on Improvement of Rheumatoid Arthritis Care in Latin America Establishing Centers of Excellence. J Clin Rheumatol 2015;21(4):175-80. doi: 10.1097/RHU.0000000000000247 [published Online First: 2015/05/27]
2. Santos-Moreno P, Caballero-Uribe CV, Massardo ML, et al. Systematic and progressive implementation of the centers of excellence for rheumatoid arthritis: a methodological proposal. Clin Rheumatol 2017;36(12):2855-58. doi: 10.1007/s10067-017-3790-7 [published Online First: 2017/08/26]
3. Santos-Moreno P, Caballero-Uribe CV, Cardiel MH, et al. A Consensus Position Paper From REAL-PANLAR Group About the Methodological Approach for the Accreditation Process of Centers of Excellence in Rheumatoid Arthritis in Latin America. J Clin Rheumatol 2019;25(1):54-58. doi: 10.1097/RHU.0000000000000773 [published Online First: 2018/03/30]
4. Barber CEH, Mosher D, Dowling S, et al. Implementation and Evaluation of Audit and Feedback for Monitoring Treat-to-Target (T2T) Strategies in Rheumatoid Arthritis Using Performance Measures. Rheumatol Ther 2020;7(4):909-25. doi: 10.1007/s40744-020-00237-0 [published Online First: 2020/10/10]
5. Barber C, Then K, Bohm V, et al. Development of a patient-centered quality measurement framework for measuring, monitoring, and optimizing rheumatoid arthritis care in Canada. J Rheumatol 2020;In Press doi: 10.3899/jrheum.200688 [published Online First: 2021/01/17]
6. Barber C, Lacaille D, Hall M, et al. Strategies for developing and implementing a rheumatoid arthritis healthcare quality framework: a thematic analysis of perspectives from arthritis stakeholders. BMJ open 2021;11(3):e043759. doi: 10.1136/bmjopen-2020-043759 [published Online First: 2021/03/07]
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...
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 various types of coagulation factors as well, but their cholesterol does not differ from that of healthy FH individuals´.6 In accordance, rabbits with FH have significantly higher levels of factor VIII and fibrinogen compared with normal rabbits and in an experiment with these rabbits, atherosclerosis was prevented with probucol, which lowered factor VIII and fibrinogen whereas their serum cholesterol was unchanged.6
A relevant question is why high LDL-C is beneficial. The cause is most likely that LDL partakes in the immune system by adhering to and inactivating all kinds of microorganisms and their toxic products; a little-known fact although it has been documented in many ways by more than a dozen research groups.7 The reason why the association between high LDL-C and mortality in the study by Jin et al. was noted only in patients with acute coronary syndrome may be that there is much evidence that infections is a major cause of CVD.8
1. Jin J, Shi Z, Pang X. Association between low- density lipoprotein cholesterol level and mortality in patients with cardiogenic shock: a retrospective cohort study. BMJ Open 2021;11:e044668. doi:10.1136/ bmjopen-2020-044668
2. Ravnskov U, Diamond DM, Hama R, et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 2016;6: e010401. doi:10.1136/ bmjopen-2015-010401
3. Ravnskov U, de Lorgeril M, Diamond DM, et al. The LDL paradox: Higher LDL-cholesterol is associated with greater longevity. A Epidemiol Public Health 2020;3:1040-7.
4. Ravnskov, Alabdulgader A, de Lorgeril M, et al. The new European guidelines for prevention of cardiovascular disease are misleading. Exp Rev Clin Pharm 2020;13:1289-94. doi.org/10.1080/17512433.2020.1841635
5. Ravnskov U, de Lorgeril M, Diamond DM, et al. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature. Expert Rev Clin Pharm 2018;11:959-70. doi: 10.1080/17512433.2018.1519391.
6. Ravnskov U, de Lorgeril M, Kendrick M, et al. Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia. Med Hypotheses 2018;121:60–3. doi.org/10.1016/j.mehy.2018.09.019
7. Ravnskov U, McCully KS. Review and Hypothesis: Vulnerable plaque formation from obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies. Ann Clin Lab Sci 2009;39:3-16. PMID: 19201735.
8. Ravnskov U, McCully KS. Infections may be causal in the pathogenesis of atherosclerosis. Am J Med Sci 2012;344:391-4. doi: 10.1097/MAJ.0b013e31824ba6e0.
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
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.  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...
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 attachment being 5 weeks in all 23 UK medical schools. With such short exposure to a large subject may encourage superficial learning which medical education is specifically trying to avoid. It is estimated that 30% of all GP consultations in the UK are Musculoskeletal, of which a quarter who visit their GP are <18 years old. [5,6,7] This is fundamentally important as 50% of all medical graduates in the UK will be training to become GPs. We believe from our clinical experience in numerous primary care and secondary care sites that observation of clinicians alone may be an ineffective method in acquiring the key skills to conduct a concise consultation.
When asked to take our first history for a child presenting with a limp in new patient clinic, we found difficulty phrasing sensitive questions about non-accidental injury, asking about childhood obesity as well as establishing a clear contralateral history from family members. This uncertainty sometimes led us to neglect certain parts of the history entirely. One case, when observing a FY2 led to a partial delay in diagnosis of an acute on chronic slipped capital femoral epiphysis (SCFE). As the plain anteroposterior radiographs of the pelvis were unremarkable as the slip was subtle and the child was not overweight, nor was there any endocrinal abnormalities such as hypothyroidism and growth hormone deficiency from the patient history. When reflecting, we feel additional techniques should be implemented in other aspects of clinical education alongside history taking under supervision in order to prevent pit-falls in core principles as a clinician. For example, practicing with simulated patients has given us a greater degree of confidence when handling difficult discussions, having an index of suspicion for abuse cases and identifying good clinical practice when communicating with children and parents. The removal of the fear factor in a safe environment prior to seeing patients additionally helped. When examining the literature further, it shows simulated patients are as effective learning resource in the orthopaedic training of undergraduate medical students as real patients.  Driving changes by Royal College of surgeons Ireland to implement more SP training as part of the undergraduate syllabus.
From Student Feedback across 5 hospital sites across the Yorkshire and Humber region, our medical school is now adopting a multi-modal approach. In which simulated orthopaedic patients has now been adopted as part of the curriculum, alongside sexual health and ABCDE masterclass SP teaching sessions. We hope our efforts provide the foundations for a more competent and confident medical students in identifying issue in relation to with a child presenting with a limp.
 Perry D C, Bruce C. Evaluating the child who presents with an acute limp BMJ 2010; 341: c4250 doi:10.1136/bmj.c4250
 1. Al-Nammari SS, Pengas I, Asopa V, Jawad A, Rafferty M, et al. (2015) The inadequacy of musculoskeletal knowledge in graduating medical students in the United Kingdom. J Bone Joint Surg Am 97: e36.
 2. Pinney SJ, Regan WD (2001) Educating medical students about musculoskeletal problems. Are community needs reflected in the curricula of Canadian medical schools? J Bone Joint Surg Am 83: 1317-1320.
 J.R. Williams. A review of undergraduate teaching in orthopaedic surgery in the United Kingdom. Orthopaedic Proceedings Vol. 85-B, No. SUPP_I. British Orthopaedic Association/Japanese Orthopaedic Association Combined Congress. 21 Feb 2018
 de Inocencio J. Musculoskeletal pain in primary paediatric care: analysis of 1000 consecutive general paediatric clinic visits. Paediatrics. 1998 Dec;102(6):E63. doi: 10.1542/peds.102.6.e63. PMID: 9832591
 De Inocencio J. Epidemiology of musculoskeletal pain in primary care. Arch Dis Child. 2004;89(5):431-434. doi:10.1136/adc.2003.028860
 Hassan Raja, Shehzaad A Khan, Abdul Waheed. The limping child — when to worry and when to refer: a GP’s guide. British Journal of General Practice 2020; 70 (698): 467. DOI: 10.3399/bjgp20X712565
 Deakin N. Where will the GPs of the future come from? BMJ 2013; 346 :f2558 doi:10.1136/bmj.f2558
 Gardiner S, Coffey F, O’Byrne J, et al. 0209 Simulated Patients Versus Real Patients As Learning Resources In The Clinical Skill Training Of Medical Students – A Randomised Crossover Trial Of Their Effectiveness. BMJ Simulation and Technology Enhanced Learning 2014;1:A23.
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
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