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Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on 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: GPs earned £90 600 on average in 2014-15 Tom Moberly. 354:doi 10.1136/bmj.i5005

Current GP locum hourly rates allow much higher incomes, these days.
Brexit is likely to increase shortages.

Competing interests: No competing interests

17 April 2017
Stavros Saripanidis
Consultant in Obstetrics and Gynaecology
Thessaloniki, Greece
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Re: Is tonsillectomy recommended in adults with recurrent tonsillitis? Jason Powell, James O’Hara, Sean Carrie, Janet A Wilson. 357:doi 10.1136/bmj.j1450

Jason Powell et al write that to get rid of ill health and pain due to recurrent tonsillitis, it is worthwhile to get total tonsillectomy done in adults. However, a very old paper by Chamovitz et al says that it does not prevent sore throats due to group A streptococcus (study was done on military men from 1949 to 1954) and hence rheumatic fever and its complications like valvular diseases.

tonsillectomy on the incidence of streptococcal respiratory disease and its
complications. Pediatrics. 1960 Sep;26:355-67.

Competing interests: No competing interests

17 April 2017
Neeru Gupta
Scientist F
KK Jani, Jugal Kishore, Akshun Jani.
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029.
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Re: Next steps on the NHS five year forward view Chris Ham. 357:doi 10.1136/bmj.j1678

The NHS Five Year Forward View (1) when published in 2014 had a major flaw, and this has yet to be noted in Ham`s Editorial as he looks at the next steps in 2017 (2).

A plan - for this is what was presented in 2014 - has, of necessity, to recognise current and near-future constraints, by making guesses about political sentiment, economic capability and sustainability. But setting off on a journey without having a pretty clear idea of the destination, a strategic view, is foolhardy. Once identified, a strategy can be folded back to the present.

The major flaw currently is the failure to identify the dominant independent variable that has - and will continue to have - the greatest impact on the efficient delivery of healthcare. This is `technological innovation`. The history of the NHS is littered with examples where the service has had to do catch-up with technology - reconfiguring its workforce, changing the way care is delivered, and redeploying capital budgets to new locations or for the development of new facilities - often years behind the curve.

Some examples include:
• A failure to anticipate the potential impact of the arrival of phenothiazines in the 1950s on the ability to discharge patients from psychiatric hospitals; and the appalling lack of community mental health services necessary to provide support for vulnerable ex-patients.
• Being unprepared to take advantage of powerful combinational developments in fibre optics and endoscopy, digital imaging and new anaesthetics that reduced nausea, resulting in delays in implementing minimal access and day case surgery.
• Failing to develop the use of telecare, and maximising the shift of available technologies to the home for those who might benefit directly by not being admitted to hospital, or allowing earlier discharge; and developing an adequate district nurse workforce to provide support.

`Substitution research` is a dynamic approach which can be used to challenge current conventional planning methods, which tend to start with a careful analysis of the existing position and so risk limiting the freedom to think creatively. This is evident in `Next steps` It is also very useful when used strategically. `Substitution` is defined as the continual regrouping of resources across and within care settings, to exploit the best and least costly solutions in the face of changing needs and demands (3). Of course this has been happening already, albeit without the title, but reactively for the most part.

One useful typology differentiates three kinds of substitution: the introduction of new technologies; moving the location at which care is given; and changing the mix of staff and skill requirements (4). It is the first of these, as the most frequent long-term independent variable, that requires constant scanning outside of the NHS itself. But with identification of technology innovations goes the consequent need to look at the implications for care location, and workforce training and planning. This is a foresight exercise of the greatest importance, and was identified as such by Sir Michael Peckham, Director of R&D for NHS England in 2000 (5) following the publication of Project SHIFT (6).

Perhaps we might start now with a recent headline in the Times: Sound-wave blood test gives results in minutes (7). It is a few years away, no doubt, but needs to be built into strategic thinking now.

Ham states that Simon Stevens, author of the Forward View and chief executive of NHS England, has `focused minds by emphasising the inevitably of hard choices in healthcare` . But this has always been the case, and has served as the bedrock of a muddling through approach. The public and demoralised healthcare professionals now urgently to be shown some light at the end of what has been a very long tunnel. This could be achieved if a systematic approach to substitution was to be employed, with future technologies given the lead role. A horizon-scanning version of NICE perhaps? Whatever, the NHS needs an evidence based Strategic Direction to give a sense of hope.

1. Five year Forward View. NHS England, Oct 2014.
2. Ham C. Next steps on the NHS Five Year Forward View. Editorial, BMJ 8 April 2017.
3. The expression was first applied to healthcare in the Dekker Report, Changing health care in the Netherlands. The Hague, Ministry of Welfare, Health and Cultural Affairs, 1988.
4. A model of the typology and a more detailed discussion of `substitution` is Warner, MM. Contribution to Saltman RB and Figueras J. European Health Care Reform: Analysis of Current Strategies. WHO Regional Office for Europe 1997, 214-217.
5. Foresight Healthcare Panel, Healthcare 2020 - Making the future Work for You. London: the Department of Trade and Industry 2000. Available at
6. Warner MM. et al, Can Home be Possible for the Frail Elderly? Substitution of Hospital and other Institutional-focused Technologies (Project SHIFT). Welsh Institute for Health and Social Care, January 2003.
7. The Sunday Times 09 April 2017.

Competing interests: No competing interests

17 April 2017
Morton M Warner
Emeritus Professor of Health Strategy and Policy
Welsh Institute for Health and Social care
Tredodridge, Vale of Glamorgan
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Re: David Oliver: Challenges for rural hospitals—the same but different David Oliver. 357:doi 10.1136/bmj.j1731


I thank Dr Syme for his intervention around Scottish population density.

There is an alternative possible explanation. i.e. that having been to Scotland many times and read my Geography books, I am well aware that a high percentage of the population is concentrated in the Central Belt, meaning that other areas such as the Highlands, Islands and Borders are much more sparsely populated.

By analogy, I am also aware that both Australia and Canada have a high percentage of their own populations concentrated in a handful of big metropolitan areas, meaning that the remote and rural areas are far less densely populated than the headline figures for the nation might suggest.

I very deliberately cited Scottish reports because Scotland has done more thinking for longer about rurality and healthcare than England.

In a 450 word column, detail is often sacrificed for narrative flow with readers free to follow links to references

David Oliver

Competing interests: No competing interests

16 April 2017
David Oliver
consultant physician
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Re: Pancreas transplantation Patrick G Dean, Aleksandra Kukla, Mark D Stegall, Yogish C Kudva. 357:doi 10.1136/bmj.j1321

Title: Pancreas Transplantation: The untold origin of the story… the pancreas Donor
Authors: IM Shapey1,2 A Summers1,2, T Augustine1,2, MK Rutter1,3, D van Dellen1,2
1) Faculty of Medicine, Biology and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester UK.
2) Department of Renal and Pancreatic Transplantation, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
3) Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Article type: Rapid response/Letter
Word Count: 916
Keywords: Pancreas, Islet, Transplantation, Donor, Insulin
Acknowledgements: We would like to recognise the important and life changing gift provided by organ donors and their families which has facilitated the possibility of pancreas transplantation.
Funding: Medical Research Council (UK); Royal College of Surgeons of Edinburgh

Main text

Dear Editor,

We read with interest Dean et. al.’s State of the Art Review of Pancreas Transplantation. It is refreshing to have pancreas and islet transplantation receiving the international attention it urgently deserves. In patients with complex diabetes mellitus, pancreas and islet transplantation can offer life-changing and life-saving therapies. Improving knowledge and understanding amongst referring physicians regarding the potential benefits of pancreas transplantation is important because current referral rates to UK pancreas transplantation centres are low and do not reflect the number that may benefit from transplantation. For many decades, pancreas transplantation has been the forgotten sibling of liver, kidney and cardio-thoracic transplantation. The amelioration of both hyper- and hypo-glycaemia and alleviation of its associated macro- and micro-vascular complications stands to benefit numerous patients affected by diabetes with significant subsequent secondary benefits for healthcare resources.

Dean’s review focuses on the indications for, and outcomes following pancreas and islet transplantation. Unfortunately, this represents only the recipient’s half of the process, and does not acknowledge the major challenges facing pancreas and islet transplantation regarding the organ donor. Pancreas donation comes predominantly from deceased individuals following declaration of neurological (brain-stem) death or donation after circulatory death (formerly known as non-heart beating donation). Living pancreas donation occurs in small numbers in select centres, but, due to the associated morbidity for the donor (15-30%), has not become standard practice internationally.[1-2]

The main factors limiting the success of pancreas transplantation historically have been difficulties in optimising donor selection and achieving successful long-term function. Inappropriate donor organ selection, due to a lack of objective clarity for quality assessment, continues to impact adversely on patient outcomes in pancreas transplantation. Two-thirds of donor pancreata offered for transplantation are currently considered unsuitable.[3] Outcomes remain far from ideal: in the UK, 6 out of 10 pancreas grafts have failed at 5 years when transplanted alone, and 3 out of 10 fail at 5 years when the pancreas is performed simultaneously with a kidney transplant, as occurs in over 80% of cases.[4] The well-documented shortage of organs for transplantation creates an urgent need to improve objective methods for selection of high quality pancreata; and also to identify the ideal physiological environment to enable a transplanted pancreas to thrive in the longer term.

Contrary to other areas of organ transplantation such as the kidney, liver and heart, there is a paucity of research and knowledge in the field of donor organ assessment and viability testing in pancreas and islet transplantation to aid in critical decision making. Reliable and validated donor risk indices exist for both liver [5] and kidney transplantation [6], but the currently available pancreas donor risk index (PDRI) [7] is unreliable. Studies attempting to validate the PDRI as a predictive tool have provided mixed results [8-12], and this may account for its low utility when compared to its liver and kidney counterparts. Apart from cold ischaemic time, the PDRI relies entirely on donor characteristics, and the variable outcomes from validation studies [8-12] are therefore possibly a reflection of the absence of any quantifiable primary measures of the function and quality of the organ itself.

Current decision-making in donor selection is a qualitative process which is multifactorial and largely subjective with significant individual clinician and centre variability. The donor factors reported to have the greatest impact on future graft loss include body mass index, [13] age, [14] donor type [7] and cold ischaemic time [13]. As the donor population grows older and larger, the negative impact of these factors on donor pancreas quality is likely to be an increasing problem. HbA1C and c-peptide are not routinely evaluated in organ donors in part due to limited local access in donor hospitals out-of-hours. Macroscopic features of the pancreas are also an important consideration; the degree of inter- and intra-lobular pancreatic steatosis, fibrosis and calcification are associated with the likelihood of reperfusion pancreatitis and poorer long-term function [15]. Currently, visual assessment coupled with palpation is the best subjective evaluation of the quality of the solid organ pancreas.

In organ donors, the process of brain stem death causes high levels of systemic catecholamines and inflammation affecting all organs [16-18]. These changes, and the routine use of high-dose corticosteroids in intensive care units (ICU) [19], leads to hyperglycaemia in around 50% of donors which is managed with insulin. Traditional teaching suggests that donor hyperglycaemia is a transient phenomenon caused by reversible insulin resistance in the donor [16]. Current and future work is identifying strategies to identify, quantify and correlate the effects of the catecholamine storm generated by brain stem death and the potential deleterious effects on beta-cell function both in the immediate and longer term.

If true progress is to be made in alleviating the devastating sequelae of diabetes, then a co-ordinated and concerted effort is required to improve the success of transplantation. This involves increasing our knowledge of the physiological behaviour of both donors and recipients along with technological advances. Doing so will allow us to identify which patient groups stand to benefit the most from transplantation and to determine which modalities of beta-cell replacement therapy (solid organ, cellular, or bio-artificial pancreas) are appropriate at a given time in a patient’s clinical journey with diabetes. Until we can achieve mass production of therapeutic grade beta-cells, which remains the holy grail of Beta cell replacement therapy, it is critical that we have strong objective criteria to assess the quality of donor pancreata which will maximise the number of patients with complex diabetes who can gain access to this state of the art therapy.

1) Kirchner VA, Finger EB, Bellin MD, Dunn TB, Gruessner RW, Hering BJ, Humar A, Kukla AK, Matas AJ, Pruett TL, Sutherland DE, Kandaswamy R. Long-term Outcomes for Living Pancreas Donors in the Modern Era. Transplantation. 2016 Jun;100(6):1322-8.
2) Matsumoto I, Shinzeki M, Asari S, Goto T, Shirakawa S, Ajiki T, Fukumoto T, Ku Y. Evaluation of glucose metabolism after distal pancreatectomy according to the donor criteria of the living donor pancreas transplantation guidelines proposed by the Japanese Pancreas and Islet Transplantation Association. Transplant Proc. 2014 Apr;46(3):958-62.
3) NHS Blood and Transplant (2016) Annual Report on The National Organ Retreival Service and Usage of Organs (2015/2016) accessed 05/04/2017
4) NHS Blood and Transplant (2016) Annual Report on Pancreas and Islet Transplantation (2015/2016) accessed 05/04/2017
5) Feng S, Goodrich NP, Bragg-Gresham JL et al Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006 Apr;6(4):783-90.
6) Rao PS, Schaubel DE, Guidinger MK, Andreoni KA, Wolfe RA, Merion RM, et al. A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation 2009;88:231-236.
7) Axelrod DA, Sung RS, Meyer KH, et al. Systematic evaluation of pancreas allograft quality, outcomes and geographic variation in utilization. Am JTransplant 2010; 10:837–845
8) Maglione M, Ploeg RJ, Friend PJ. Donor risk factors, retrieval technique, preservation and ischemia/reperfusion injury in pancreas transplantation. Curr Opin Organ Transplant. 2013 Feb;18(1):83-8
9) Mittal S, Lee FJ, Bradbury L, Collett D, Reddy S, Sinha S, Sharples E, Ploeg RJ, Friend PJ, Vaidya A. Validation of the Pancreas Donor Risk Index for use in a UK population. Transpl Int. 2015 Sep;28(9):1028-33.
10) Amaral PH, Genzini T, Perosa M, Massarollo PC.Donor risk index does not predict graft survival after pancreas transplantation in Brazil. Transplant Proc. 2015 May;47(4):1025-8.
11) Blok JJ, Kopp WH, Verhagen MJ, Schaapherder AF, de Fijter JW, Putter H, Ringers J, Braat AE. The Value of PDRI and P-PASS as Predictors of Outcome After Pancreas Transplantation in a Large European Pancreas Transplantation Center. Pancreas. 2016 Mar;45(3):331-6.
12) Finger EB, Radosevich DM, Dunn TB, Chinnakotla S, Sutherland DE, Matas AJ, Pruett TL, Kandaswamy R. A composite risk model for predicting technical failure in pancreas transplantation. Am J Transplant. 2013 Jul;13(7):1840-9.
13) Humar A, Ramcharan T, Kandaswamy R, Gruessner RW, Gruessner AG, Sutherland DE. The impact of donor obesity on outcomes after cadaver pancreas transplants. Am J Transplant 2004; 4: 605-10
14) Salvalaggio PR, Schnitzler MA, Abbott KC, et al. Patient and graft survival implications of simultaneous pancreas kidney transplantation from old donors. Am J Transplant 2007; 7: 1561-71
15) van Dellen D, Summers A, Trevelyan S, Tavakoli A, Augustine T, Pararajasingam R. Incidence and Histologic Features of Transplant Graft Pancreatitis: A Single Center Experience. Exp Clin Transplant. 2015 Oct;13(5):449-52.
16) Masson F, Thicoipe M, Gin H, de Mascarel A, Angibeau RM, Favarel-Garrigues JF, Erny P.. The endocrine pancreas in brain-dead donors. A prospective study in 25 patients. Transplantation. 1993;56:363-7.
17) Contreras JL, Eckstein C, Smyth CA, Sellers MT, Vilatoba M, Bilbao G, Rahemtulla FG, Young CJ, Thompson JA, Chaudry IH, Eckhoff DE. Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats. Diabetes. 2003;52(12):2935-42.
18) Rech TH, Crispim D, Rheinheimer J, Barkan SS, Osvaldt AB, Grezzana Filho TJ, Kruel CR, Martini J, Gross JL, Leitão CB. Brain death-induced inflammatory activity in human pancreatic tissue: a case-control study. Transplantation. 2014 ;97:212-9.
19) Geer EB, Islam J, Buettner C.Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue function and lipid metabolism. Endocrinol Metab Clin North Am. 2014;43(1):75-102.
20) Shapey IM, Summers AM, Augustine T, Rutter MK, van Dellen D. Circulating Cell-Free Unmethylated DNA as a Marker of Graft Dysfunction in Pancreas Transplantation. Am J Transplant. 2016 16: 3064–3065
21) Quality in Organ Donation Consortium (2016) accessed 05/04/2017

Competing interests: Funding (IS): Medical Research Council (UK); Royal College of Surgeons of Edinburgh

16 April 2017
Iestyn M Shapey
MRC Clinical Research Training Fellow
Angela Summers; Titus Augustine; Martin Rutter; David van Dellen
University of Manchester
Oxford Road, Manchester, UK M13 9PL
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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

Many thanks for your reply - it is great to see detailed responses from authors and I commend them for their responses (and speed of response).

I understand the matching better now, but still feel that we are unlikely to completely match accurately and there will be a degree of confounding, however, I think we may never agree!

And many thanks for calculating correct NNH - I slightly overestimated my figures.

Competing interests: No competing interests

16 April 2017
Medical Trainee
Weston Area Health Trust
Weston General Hospital, W-S-M, BS23 4TQ
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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.


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 (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
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.


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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