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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: “Golden hello” of £20 000 to be offered to 200 GPs a year, says health secretary Zosia Kmietowicz. 359:doi 10.1136/bmj.j4759

Sadly this does not fill me with enthusiasm. As a partner in a GP practice which employs several salaried GPs, I've been involved with tough discussions over salaries for the GPs we employ, pay scales they expect are rising and as a result this has eroded the 'profit share' of partners.

Also as a 60yr old GP, I've been disheartened by the lack of response from the BMA over the government's decision to withdraw seniority. As a result my income will gradually reduce by a further £10,000 over the next few years.

As well as encouraging young doctors into General Practice, the government should be endeavouring to stop the 'brain drain' of senior GPs as they seek to take early retirement through increasing disillusionment.

Competing interests: No competing interests

19 October 2017
Colin K Flenley
Portland Medical Practice, Aldridge, Walsall
Re: Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13 Ashlyn Pinto, Ajay Aggarwal, et al. 359:doi 10.1136/bmj.j4530

In their recent paper in the BMJ (1) Davis et al. have used the ESMO-MCBS to evaluate the level of clinical benefit of anticancer agents licensed between 2009-2013. While we laud them on this project and agree with the general conclusion that many treatments with very limited evidence for benefit are licensed, part of their analysis is based on a flawed understanding of the ESMO-MCBS scale.

The statement in the methods section: “Only scores of A or B (for treatments of curative intent), or 5 or 4 (for treatments used in the non-curative/palliative setting) are defined as clinically meaningful according to the ESMO framework.” is not an accurate representation. Indeed, it perpetuates a common misunderstanding of the ESMO-MCBS grading. While the ESM0-MCBS does distinguish high benefit from low benefit studies, it does not set a threshold for “clinical meaningfulness” (2-4).

While scores of A or B (for treatments of curative intent), or 5 or 4 (for treatments used in the non-curative/palliative setting) indicate “a high level of proven clinical benefit” or “substantial benefit”, this does not preclude that studies achieving slightly lower scores, such as a grade of 3 in the non-curative/palliative setting, may also provide clinically meaningful benefit. Indeed, a study correlating the decisions of the Israeli HTA body to ESMO-MCBS scoring found that in the non-curative setting, most medications with a score of >3 were approved for reimbursement whereas those with a score of <3 were very rarely approved (5). This experience would indicate that in a high income country, scores of >3 were usually judged by an experienced HTA body to be clinically meaningful, and worthy of reimbursement in a resource limited environment (5).

Accurate interpretation of the results generated by the ESMO-MCBS require methodological diligence in data acquisition, careful application of the tool, and a clear understanding of the meaning (and acknowledged limitations) of the grades generated (2-4).

1. Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ 2017;359:j4530
2. Cherny N, Dafni U, Bogaerts J, Latino N, Piccart M, Pentheroudakis G, et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017:mdx310,
3. Cherny NI, Sullivan R, Dafni U, Kerst JM, Sobrero A, Zielinski C, et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015;26:1547-73.
4. Dafni U, Karlis D, Pedeli X, Bogaerts J, Pentheroudakis G, Tabernero J, et al. Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules. ESMO Open. 2017;2(4). e000216; DOI: 10.1136/esmoopen-2017-000216
5. Hammerman A, Greenberg-Dotan S, Feldhamer I, Birnbaum Y, Cherny NI. The ESMO-Magnitude of Clinical Benefit Scale for novel oncology drugs: correspondence with three years of reimbursement decisions in Israel. Exp Rev Pharmacoecon Outcomes Res 2017:1-4. doi: 10.1080/14737167.2017.1343146

Competing interests: No competing interests

19 October 2017
Nathan I. Cherny
Medical Oncologist
Urani a Dafni, Jan Bogaerts, Nicola.J. Latino, George Pentheroudakis, Jean-Yves Douillard, Josep Tabernero, Christoph Zielinski, Martine J. Piccart, Elisabeth.G.E. de Vries
Shaare Zedek Medical Center and ESMO Magnitude of Clinical Benefit Working Group
Jerusalem, Israel and Lugano, Switzerland
Re: Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study J Michael Paterson, Colin R Dormuth, Pierre Ernst, Shenzhen Yao, et al. 359:doi 10.1136/bmj.j4323

What would also be very interesting, in addition to the results presented in this study, is the bleeding and mortality associated with emergent surgical intervention (and morbidity caused by delayed surgery secondary to DOAC anticoagulation). Many patients are unaware that there is not always an immediate reversal agent for a DOAC, and on discovering this they choose to stay on Warfarin.

Competing interests: No competing interests

19 October 2017
Sherief Elsayed
Consultant Spinal Surgeon
Re: NHS boss reveals loss of further 162 000 pieces of medical correspondence Gareth Iacobucci. 359:doi 10.1136/bmj.j4822

As a selfish person (perhaps unique?), may I suggest that in England, EVERY general practice and EVERY hospital should write to their patients in the following terms:

Dear Mr Smith, or Hunt or Patel

We know that despite our supremely efficient services, close to a million letters have gone missing. One or more could have been about you or to you

We suggest that you write to us (and please send a copy to your solicitor) to ask us whether any of the missing correspondence was to you or about you.

We will then know that you are interested in your health. We are so short of staff that we will not bother to contact you unless we receive a request from you.

Yours, helplessly

Devoted servant of the State

Competing interests: No competing interests

19 October 2017
JK Anand
Retired doctor
Free spirit
Re: Reassurance for many healthy women considering HRT Chrisandra Shufelt, C Noel Bairey Merz. 359:doi 10.1136/bmj.j4652

Further to JK Anand's queries on HRT, how many 'bothersome' menopausal symptoms occur because women's bodies have become used to the same or similar hormones given for hormonal contraception? These sex steroid hormones are frequently given for years before menopause and it would not be a surprise for unpleasant physiological reactions to occur when levels are lowered. If this is correct, one drug is being given to counteract the side effects of withdrawal from another.

Competing interests: No competing interests

19 October 2017
Elizabeth Price
Retired medical practitioner
London NW11
Re: Incidence, clinical management, and mortality risk following self harm among children and adolescents: cohort study in primary care Jonathan Green, Carolyn A Chew-Graham, Nav Kapur, Darren M Ashcroft, et al. 359:doi 10.1136/bmj.j4351

There is an obvious reason for the observations of Morgan and colleagues.1 The annual incidence of self-harm increasing three times more in girls (37.4 per 10 000) than boys (12.3 per 10 000), and, the sharp 68% increase in girls aged 13-16, from 45.9 per 10 000 in 2011 to 77.0 per 10 000 in 2014, are likely to reflect an increased exposure to progestogens in hormonal contraceptives.

We discovered in the 1960s that powerful progestogens increase endometrial, blood and brain levels of enzyme monoamine oxidase which increases the risk of depression.2,3

Mental illnesses such as depression, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), eating disorders, personality disorders, and autism spectrum disorders, conduct disorder, schizophrenia spectrum disorders, obsessive compulsive disorder, bipolar disorder, tics, and social dysfunction, are also more common in children born to mothers who continue to take antidepressants during pregnancy and probably previously took progestogens for contraception.4

The cost of reducing teenage pregnancies is high as long-acting reversible contraceptives (LARCs) - injectables, implants, intrauterine devices and systems - are used to discourage early discontinuations of OCs for depression or weight gain. Very high progestogen doses given for morning after emergency contraception can cause severe migraine and vomiting in my experience. Steroid abuse has been added to sexual abuse. The numbers of teenage pregnancies increased sharply due to the Pill-induced “sexual revolution” as the age of first sex has reduced. Use of powerful carcinogenic. psychoactive progestogens has caused huge problems for future generations. Mental health services are failing to meet soaring demand.5

1 Morgan C, Webb RT, Carr MJ, et al. Incidence, clinical management, and mortality risk following self harm among children and adolescents: cohort study in primary care. BMJ 2017; 359 doi: (Published 18 October 2017). BMJ 2017;359:j4351
2 Grant ECG, Pryse-Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968;3:777-80
3 Grant EC. Hormonal contraception and its association with depression. JAMA Psychiatry. Published online February 1, 2017. doi:10.1001/jamapsychiatry.2016.3701
4 Liu X, Agerbo E, Instrup KG, et al. Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study
BMJ 2017; 358: j3668 (Published 06 Sep 2017)
5 Dubicka B, Bullock T. Mental health services for children fail to meet soaring demand. BMJ 2017;358:j4254

Competing interests: No competing interests

19 October 2017
Ellen C Grant
Physician and medical gynaecologist
Kingston-upon-Thames, UK
Re: Antiretroviral therapy in pregnant women living with HIV: a clinical practice guideline Florence Anam, Teresia Otieno, Gordon H Guyatt, Graham P Taylor, et al. 358:doi 10.1136/bmj.j3961

Two national guidelines committees have released statements in response to these recommendations by Siemieniuk et al. Both committees continue to recommend the use of tenofovir disoproxil fumarate:

British HIV Association:

US Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission:

Competing interests: I serve on the US Department of Health and Human Services Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.

19 October 2017
Andrea L Ciaranello
Massachusetts General Hospital
50 Staniford St., Boston, MA, 02114
Re: David Oliver: Challenging the victim narrative about NHS doctors David Oliver. 359:doi 10.1136/bmj.j4304


I thank Jay llangaratne for his response. However, I chose my words very carefully in the article. Doctors in the BMA were indeed highly influential at ever turn

The decision to walk away from negotiation initially
The decision to re-engage
The decision to call a strike ballot
The decision to meet and negotiate with Sir David Dalton and with ACAS
The decision to call a second strike ballot
The decision having gained a number of concessions in negotiations to reject the final offer on the table
The decision to communicate internally on WhatsApp
The decision by a member of the group to leak WhatsApp conversations
The decision to recommend acceptance of the final contract

As I say, the decisions and communications were influential at every stage.

David Oliver

Competing interests: No competing interests

19 October 2017
David Oliver
Consultant Physician
Re: UK government to reclassify pregabalin and gabapentin after rise in deaths Gareth Iacobucci. 358:doi 10.1136/bmj.j4441

The Toxicology Unit, Imperial College London, conducts toxicology analysis on behalf of Coroners throughout London and the South East, handling approximately 2,500 cases per annum. In response to the growing concern over the misuse of pregabalin and gabapentin reported by Public Health England in 2014 [1] and the increase in the number of deaths with pregabalin and gabapentin recorded on the death certificate [2], analysis for pregabalin and gabapentin was introduced for all Coroners’ cases over the age of 16 years that required a general drugs screen in January 2016. Since the start of the screening programme, gabapentin and/or pregabalin has been regularly detected primarily in combination with other drugs, and often detected unexpectedly. Many laboratories only selectively screen for gabapentin and pregabalin in post-mortem cases due limited funds or regulations/accreditation [3 4] which means the number of gabapentin and pregabalin deaths may be being underestimated.

In view of our findings to date, we recommend that toxicological screening for Coroners cases should routinely include pregabalin and gabapentin in order to investigate the extent of their misuse. Our data supports the reclassification of pregabalin and gabapentin to class C controlled substances5.

1. Public Health England. Advice for prescribers on the risk of the misuse of pregabalin and gabapentin. 2014 . Available from:
2. Office of National Statistcs. Deaths related to drug poisoning in England and Wales: 2016 registrations. 2017. Available from:
3. Elliott SP, Burke T, Smith C. Determining the toxicological significance of pregabalin in fatalities. Journal of forensic sciences. 2017;62(1):169-73.
4. Eastwood JA, Davison E. Pregabalin concentrations in post-mortem blood—a two year study. Forensic science international.2016;266:197-201.
5. Iacobucci G. UK government to reclassify pregabalin and gabapentin after rise in deaths. Bmj. 2017;358:j4441.

Competing interests: No competing interests

19 October 2017
Limon K Nahar
Rebecca Andrews, Kevin G Murphy, Sue Paterson
Imperial College London
Toxicology Unit, Imperial College London, London, UK, W6 8RP
Re: Can we usefully stratify patients according to suicide risk? Matthew Michael Large, Christopher James Ryan, Gregory Carter, Nav Kapur. 359:doi 10.1136/bmj.j4627

It would be very helpful to know if the same uncertainty surrounds similar attempts to stratify patients according to their risk of homicide or serious violence to other persons. Healthcare providers often include such tools in their risk management protocols or policies, while experienced clinicians doubt their clinical utility. Which side is more likely to be correct?

Competing interests: No competing interests

19 October 2017
Keith E Dudleston
Retired psychiatrist