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Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on thebmj.com. Although a selection of rapid responses will be included online and in print as readers' letters, their first appearance online means that they are published articles. If you need the url (web address) of an individual response, perhaps for citation purposes, simply click on the response headline and copy the url from the browser window. Letters are indexed in PubMed.

Re: Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study Joshua D Stein, Rory M Marks, John Z Ayanian, Brahmajee K Nallamothu, et al. 357:doi 10.1136/bmj.j1415

Dear Dr. Hamilton,

Thank you for your review of our paper on April 13th, 2017.

You highlight some important points.

Some of these points were brought up during the peer review process and these were some of our responses.

Comments regarding confounding:
If the concern is that the patient has an underlying condition such as asthma, the SCCS design incorporates a within-person comparison. So, if the patient had asthma for 5 years, this is held constant – and is completely controlled for in the analysis. The patient had asthma at the time of the adverse event and the patient had asthma during the comparison (control) period. However, if the patient just recently developed asthma immediately after receiving the corticosteroids, then asthma would not be controlled for. In that case, though, the asthma developed after giving the corticosteroids so that having concurrent asthma was not an “indication” for prescribing the drug. The SCCS design is very powerful in controlling for underlying comorbidities in a patient. If there are immediate changes in the patient’s underlying comorbidities at the time of the prescription, then there would be a concern.

Furthermore, we performed an analysis to determine the likelihood that we were detecting adverse events as a result of “being ill” rather than exposure to corticosteroids. For this analysis, we compared 30-day rates of hospitalization for sepsis, VTE, and fractures following a clinic visit in patients with matched diagnoses who did not receive corticosteroids to those who did receive corticosteroids. In this “between person” comparison, we found that rates of adverse events were consistently higher among those who received corticosteroids. It is important to note that this finding loses the advantages of the self-controlled case series design in which each patient serves as her (or his) own control. However, it provides further evidence that our findings are unlikely to be due to increased surveillance after being ill. This is shown in Table 5 of the supplemental section.

In addition, we examined the pattern of adverse events across the indications for treatment and, importantly, found consistency regardless of the indication using the SCCS (within-person) design. For this analysis, we created two groups of patients based on their indication for receiving corticosteroids: 1) respiratory conditions and 2) musculoskeletal conditions. As the reviewer suggests, sepsis might be more common after respiratory conditions if a misdiagnosis of infection occurred; however, this would not explain the higher rates of VTE or fractures after corticosteroid exposure that we also discovered. Similarly, we noted higher rates of sepsis and VTE that would not be expected after a misdiagnosis of fracture for musculoskeletal conditions like back pain. We believe the consistency of our finding for adverse events across indications supports our hypothesis of a causal association. Table 4 of the manuscript.

Regarding your concern about mechanisms of action and biological plausibility, references have been provided regarding the biological plausibility of acute effects of corticosteroids even with short durations of treatment on key pathophysiological processes. Specifically, an article by Ton et al. showed that even a very low-dose of prednisone can change indices of bone formation and bone resorption. Pouw et al. in their article in BMJ reported that even inhaled corticosteroids with much lower levels of systemic absorption reduce biological markers of bone formation. Additional references have also been provided for VTE and Infections in the original manuscript.

We agree that the balance of benefit versus risk is important when considering corticosteroids. We list the incidence rates of adverse events for corticosteroid users and nonusers, in Table 2. From these figures, the NNH can be naively calculated for the overall sample (1178 for sepsis, 461 for venous thromboembolism and 141 for fractures). However, these figures capture all events across all presenting conditions in a year. This is less relevant for individuals who are taking a short course of corticosteroids and presumably have a transient risk from this exposure. To make this more consistent for a single clinic visit within a defined time period, one could also calculate the rates in the 5 to 90 days after a visit (only in those patients with visits). When limited to this group, the comparison rates for steroid users versus nonusers for sepsis were 0.05% versus 0.02%, for venous thromboembolism were 0.14% versus 0.9%, and for fracture were 0.51% versus 0.39% with corresponding NNHs of approximately (sepsis 3333, venous thromboembolism 2000, and fracture 833). Of course, these estimates are not from the SCCS analysis which was our key method for addressing confounding and do not take into consideration the likelihood of wide individual variation in these risks.

Overall, we believe the answers we provide above raise additional concerns when translating these findings into a simple NNH for clinicians. Although we understand the value of such simplicity in messaging our findings, we are concerned that they discount much of the complexity in the relationship between corticosteroids and adverse events.

In summary, we believe there are short-term risks of taking these medications. Additional studies are needed to confirm these findings and to evaluate optimal dosing of steroids. We believe physicians should consider using alternative therapies when available.

Best,

1) Ton FN, Gunawardene SC, Lee H, Neer RM. E ects of low-dose prednisone on bone metabolism. J Bone Miner Res 2005;20:464-70. doi:10.1359/JBMR.041125.
2) Pouw EM, Prummel MF, Oosting H, Roos CM, Endert E. Beclomethasone inhalation decreases serum osteocalcin concentrations. BMJ 1991;302:627-8. doi:10.1136/bmj.302.6777.627.

Competing interests: No competing interests

15 April 2017
Akbar K Waljee
Assistant Professor
Mary Rogers, Brahmajee Nallamothu (On behalf of all the authors)
Ann Arbor MI USA
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Re: Decriminalisation of abortion Clare Dyer. 356:doi 10.1136/bmj.j1485

The contended issue of abortion is riddled with terminology that is contradictory, obsolete, ambiguous and misleading [1]. In an otherwise informative article about proposals for the decriminalisation of the safe decisions made by women to end unwanted pregnancy, it was disappointing that the BMJ eschewed crystal-clear language; regarding two recent prosecutions of vulnerable women who obtained pills to carry out abortions, these were described as “late-term” [2]. The obstetric phrase makes no sense here (excepting for its propaganda value) [3]: ‘Term’ is the period of gestation between 37 and 42 weeks, and ‘late’ is a value judgement. ‘Late-term’ can only refer to a delivery or comparison of induction of labour at, say, 41+ weeks compared to ‘early-term’ before 39 weeks [4]. If one woman expressed a wish for an abortion at 7 weeks but didn’t obtain it until 15 weeks, that might be considered ‘slow’, and certainly ‘later’ than needed. If another was only aware she was pregnant at 15 weeks, but made a settled decision and obtained an abortion by 16 weeks, that might be consider ‘prompt’. Gestation can, and should, simply be described as a length of time of pregnancy, whether in days, weeks or trimesters.

[1] Grimes DA, Stuart G. Abortion jabberwocky: the need for better terminology. Contraception 2010; 81:93-96
[2] Dyer C. Abortion decriminalisation. BMJ 2017;356:j1485
[3] Stein R. Slaying of George Tiller Focuses Attention on Late-Term Abortions Friday, June 5, 2009 http://www.washingtonpost.com/wp-dyn/content/article/2009/06/04/AR200906... (accessed 14 April 2017)
[4] Walker KF, Bugg GJ, Macpherson M, McCormick C, Grace N, Wildsmith C, Bradshaw L, Smith GCS, Thornton JG. Randomized Trial of Labor Induction in Women 35 Years of Age or Older N Engl J Med 2016; 374:813-822

Competing interests: No competing interests

15 April 2017
Susan Bewley
Professor of Women's Health
Kings College London
10th floor north wing, St Thomas' Hospital, Westminster Bridge Rd
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Re: New concepts in the management of restless legs syndrome Diego Garcia-Borreguero, Irene Cano-Pumarega. 356:doi 10.1136/bmj.j104

We were surprised that a review entitled "Managing Restless Legs Syndrome" had no primary care contributing author. As a medical student and a senior GP we would suggest that the recent welcome emphasis on improving recruitment to primary care should include ensuring that reviews of conditions, like restless leg syndrome, which are commonly seen and treated in primary care include primary care authors.

Whilst a discussion of new concepts in the treatment of such conditions is interesting and valuable, many patients do not need new treatments. The review article refers to much more expensive dopamine agonists but does not mention the cost effective first line use of low dose co-beneldopa, which one of us has used for many patients over many years.
Whilst augmentation and loss of efficacy are recognised issues with the use of dopamine agonists, experience has shown that intermittent use of these drugs can avoid these problems. The addition of a GP author in such reviews might ensure that cost is a consideration.

Routinely including at least one GP author in articles about common conditions presenting in primary care would both improve the relevance of reviews and perhaps encourage medical students to consider this interesting and rewarding branch of medicine as a career.

Competing interests: No competing interests

15 April 2017
Philip J Taylor
Senior GP
Thomas Taylor 5th year medical student Oxford Univeresity
Axminster Medical Practice
Church St Axminster
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Re: Impact of total knee replacement practice: cost effectiveness analysis of data from the Osteoarthritis Initiative Sita M A Bierma-Zeinstra, Madhu Mazumdar, et al. 356:doi 10.1136/bmj.j1131

Letter to the Editor
BMJ
April 15, 2017

To the Editor:

As the Principal Investigators of the Multicenter Osteoarthritis Study (MOST), which was used as part of the analysis for a recent BMJ paper by Feket and colleagues,1 we want to highlight a problem that we believe calls into question the validity of the results of the paper. This paper1 suggested that total knee replacement (TKR) for many persons may not be cost-effective because persons undergoing these operations may not have sufficient pain or functional loss prior to surgery to benefit greatly from these surgeries. To arrive at this conclusion, Ferket and colleagues used data from the Osteoarthritis Initiative (OAI) where there were yearly assessments of pain and functional limitation and from the MOST study where there was a baseline evaluation followed by a subsequent evaluation 30 months later.

In their first adjusted model, the investigators only included baseline measures of pain and function, which could be up to 8 years prior to surgery, to estimate the benefits of TKR. In a model adjusted for time-varying factors, measures of pain and function up to 1 year before total knee replacement were used in the OAI study and for MOST, the measure of pain and function was drawn from the baseline examination which was up to 30 months before the TKR to assess the potential benefits of this procedure. This approach assumes that pain and functional status in persons with knee osteoarthritis are constant within these time-frames without worsening before a person undergoes a knee replacement.

Usually, patients undergo total knee replacement when their pain and function worsen. The assessments of pain and function up to 1-2.5 years prior to TKR in these studies in no way reflected that worsening except if the knee replacement was completed soon after the baseline examination. Studies from both Osteoarthritis Initiative (2) and MOST (3) have shown convincingly that in the months preceding total knee replacement, there is a marked worsening in the trajectory of pain and function (see for example, Figure 2 in Collins et al). This contradicts the basic assumption in the Ferket et al. study that there was unlikely to be much short-term worsening prior to TKR. It is not surprising that other studies which collected data on pain and function just before TKR have reported much more favorable effects of TKR on pain and function outcomes,

As part of a sensitivity analysis Ferket and colleagues report that when pain and function are worse, knee replacements become cost-effective in their calculations. We strongly suggest that pain and function are usually worse in patients approaching TKR than the values used by Ferket and colleagues in their study. This would change the message of the paper and suggests, as previous studies have also reported, that total knee replacement is a cost-effective (4) operation.

Sincerely,

David T. Felson, MD, MPH, Boston University
Tuhina Neogi, MD, PhD, Boston University
Michael Nevitt, PhD, University of California, San Francisco
James Torner, PhD, University of Iowa
Neil Segal, MD, University of Kansas
C. Elizabeth Lewis, MD, University of Alabama, Birmingham
Principal Investigators of the MOST Study

1. Ferket BS, Feldman Z, Zhou J, et al. Impact of total knee replacement practice: cost effectiveness analysis of data from the Osteoarthritis Initiative. BMJ 2017;356:j1131.
2. Collins JE, Katz JN, Dervan EE, et al. Trajectories and risk profiles of pain in persons with radiographic, symptomatic knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthritis Cartilage 2014;22(5):622-630. doi: 10.1016/j.joca.2014.03.009
3. Oiestad BE, White DK, Booton R, et al. Longitudinal course of physical function in people with symptomatic knee osteoarthritis: Data From the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 2016;68(3):325-331.
4. Losina E, Walensky RP, Kessler CL, et al. Cost-effectiveness of total knee arthroplasty in the United States: patient risk and hospital volume. ArchInternMed 2009;169(12):1113-1121.

Competing interests: No competing interests

15 April 2017
David T Felson
professor of medicine
See end of letter
Boston University School of Medicine
Suite 200, 650 Albany Street
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Re: High integrity mental health services for children: focusing on the person, not the problem R Norman, P Fonagy, A Feltham, et al. 357:doi 10.1136/bmj.j1500

Re: Mental Health Services for Children: focus on the person, not the problem, BMJ 2017;356:j1500.

Wolpert and colleagues’ article discusses input from non-healthcare professionals and some available resources. It may be timely to remind all readers that MindEd e-learning (https://www.minded.org.uk ) is available for 'all who work with children'. There are over 330 short modules and sections, now accessible via e-learning-for-health. The award-winning MindEd for Families section of the website has over 30 modules for parents and carers, written by parents and experts and with a Flesch Reading Age of 12 years (so comprehensible by young people). Most is free to access and has become a valuable resource often recommended – and appreciated - in children’s healthcare consultations. MindEd hosting is moving from RCPCH to RCPsych as the brand is expanding to address mental health in other age-groups.

Dr Alistair Thomson, Hon.FRCPCH, and Consortium Executive MindEd.

Competing interests: AT is Consortium Executive and Chair of MindEd, but has no direct financial interest or benefit from this role. Sessional time is reimbursed from MindEd to his employing Trust.

15 April 2017
Alistair Thomson
Consultant Paediatrician and Consortium Executive MindEd
Royal College of Paediatrics and Child Health, Theobalds Road, London
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Re: David Oliver: Challenges for rural hospitals—the same but different David Oliver. 357:doi 10.1136/bmj.j1731

It's good to see rurality being addressed in the BMJ and David Oliver makes many reasonable points. However in suggesting that Scotland isn't sparsely populated I suggest he is making a fairly fundamental error. A large proportion of the Scottish population lives in the central belt, between Edinburgh and Glasgow The quoted population density for Glasgow is 3,400/sq.km. This is quite a bit higher than for Highland region, which covers a third of the land area of Scotland, has an overall population density of 9.1, and has areas within it with population densities of 4.3 (Lochaber) and 2.3 (Sutherland) - which is even lower than that quoted for Australia. There is also a skewed population in these areas with slightly greater numbers of the very old and fewer in "middle age" .

As Oliver recognises, current measures of Deprivation fail to capture significant levels of scattered deprivation, amongst the holiday homes and affluent retirees, so that attention may be focussed more on initiatives like the excellent, and badly needed, "Deep End" project in Glasgow while miss the equally intransigent problems of rural areas.

Transport is generally poor, making access to health care problematic where many people live more than two hours by road from hospital. Current policies for Emergency Care focus on a 45 minute transport time to hospital - one way - and seem to fail to recognise that helicopters generally have as long an outward journey as an inbound one.

Maybe it's time that rural healthcare got the attention it deserves?

David Syme MBChB FRCGP
Killin Perthshire Pop density about 30/sq km

http://worldpopulationreview.com/world-cities/glasgow-population/
http://www.highland.gov.uk/info/695/council_information_performance_and_...

Competing interests: No competing interests

15 April 2017
David M Syme
Locum/OOH GP
Killin Perthshire
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Re: Doctors can withdraw life support from baby with rare genetic disorder, says judge Clare Dyer. 357:doi 10.1136/bmj.j1857

The summary ruling by Mr Justice Francis can be found at

http://www.mirror.co.uk/news/uk-news/charlie-gard-ruling-read-full-10202972

The decision does not hinge on whether Charlie Gard could be kept alive – it seems to essentially hinge on:

‘But if Charlie's damaged brain function cannot be improved, as all agree, then how can he be any better off than he is now, which is a condition that his parents believe should not be sustained?’

Our judges are required to apply laws, and those laws effectively include within them the 'ethical principles which the judge must apply': in his summary ruling, Mr Justice Francis explains that point.

Competing interests: No competing interests

15 April 2017
Michael H Stone
Retired Non Clinical
None Private Individual
Coventry CV2 4HN
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Re: How to read a forest plot in a meta-analysis Philip Sedgwick. 351:doi 10.1136/bmj.h4028

Dr. Sedgwick writes as regarding inclusion of participants in the studies included for the meta-analysis, as follows:

"Randomised controlled trials were included if the intervention consisted of seven days or more of eradication therapy, and if the control treatment was placebo or no treatment. Participants were adults who tested positive for H pylori. They were otherwise healthy and asymptomatic at baseline and were followed "for" two or more years. The primary outcome was the diagnosis of gastric cancer."

Here we have an objection that the follow-up period is important in making a diagnosis of cancer. It should not be two years or more.Two years is too less a period in development of cancer. It should be rather "from" (instead of "for") two years and more.

Competing interests: No competing interests

15 April 2017
Neeru Gupta
Scientist F
Jugal Kishore.
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029.
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Re: A bleeding socket after tooth extraction Isabelle J Moran, Libby Richardson, Manolis Heliotis, Alex Bewick. 357:doi 10.1136/bmj.j1217

Dear Editors

I am writing in response to Dr Thomas' rapid response, where he is lamenting the soon-to-be-passing generation of "simpletons" (his phrasing) who were used to manage gum bleeding from teeth extraction, pulled elbow of tots, ingrown toenail (you may call it onychocryptosis or unguis incarnates but it will only be helpful in scrabbles or trivia pursuit - medical edition).

During the course of my orthopaedic training in Australia, I have been asked to see all the conditions Dr Thomas listed: sports injuries, bleeding noses, ingrowing toe nails, boils on bums, and childrens’ ‘pulled elbows, bleeding gums*

* no, not from tooth extraction, but mandible fracture. Why, you may ask? I don't know how the referring doctor seemed to think a fractured jaw should be managed by an orthopod, but then I was also once asked to see a patient with a fractured penis (not a joke): such is the state of medicine in current times.

The reflex "referring on" behaviour is particularly sad considering Prof John Murtagh's (relatively recent) classic text described the practical management of all these conditions. Entitled "General Practice" now in its 6th Edition, it is one of the more helpful and practical books GP trainees in Australia can use to learn and manage what used to be bread and butter primary care conditions.

It is even more distressing if you know that until recently Sports Physicians in Australia are mostly fellows of Royal Australian College of General Practitioners (for purposes of billing with Medicare) with special interests and training in sports conditions; now there is a separate direct pathway to Fellowship of the Australasian College of Sport and Exercise Physicians which allows Medicare billing.

I cannot speak on behalf of my orthopaedic colleagues in Mother England or Down Under, but for myself I am very happy for the competent GP (and even the competent emergency physician) to manage uncomplicated sports injuries, bleeding noses, ingrowing toe nails, boils on bums, and childrens’ ‘pulled elbows, bleeding gums without my involvement.

And on the subject of sports injury, for the record, I consider most acute isolated ATFL ruptures (often found on ultrasound for unknown indication) part of the spectrum of a common condition known as "a bad ankle sprain"; many of which can be appropriately managed non-operatively with RICE therapy with or without physiotherapy over 2-3 months.

(I apologise for misusing this platform for my soapbox stance)

Competing interests: No competing interests

15 April 2017
Shyan Goh
Orthopaedic Surgeon
Sydney, Australia
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Re: Alternative surgical training model will be trialled from 2018 Abi Rimmer. 357:doi 10.1136/bmj.j1883


Healthcare is a profound process that alters both physician and patient. Medical education is a demanding, exacting, life-altering process that trains physicians to alter the patient's anatomy (surgery) and physiology (medicine). Anatomical alterations are the exclusive domain of surgeons, whose training is the longest and most demanding of all specialties. Surgeons require not just knowledge, but also strength, stamina, speed, dexterity, and acuity. Surgery is so central to healthcare that the history of surgery is the history of healthcare.


Competing interests: No competing interests

14 April 2017
Hugh Mann
Physician
Retired
New York, NY, USA
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