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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: Jeffrey Tate Penny Warren. 357:doi 10.1136/bmj.j2937

In the obituary for Jeffrey Tate, it is stated that Dr. Tate directed Handel's [opera] Dido and Aeneas.

As is extensively documented, Handel "borrowed" and recycled music by other composers, typically modifying their music while doing so. However, there seems to be no example of his appropriating a whole opera by another composer, without attribution - in this case, a work by Henry Purcell.

If Purcell (1659-1695) had lived longer, it is conceivable that he might have established a self-sustaining tradition of opera in English. Handel might also have been able to establish such a tradition if his secular "oratorios" Semele and Hercules had not had to wait until the 20th century before becoming widely appreciated.

Competing interests: No competing interests

19 June 2017
Martin F Heyworth
Physician and composer
Department of Veterans Affairs Medical Center, Philadelphia, and Department of Medicine, University of Pennsylvania
Research Service (151), VA Medical Center, University and Woodland Avenues, Philadelphia, PA 19104, USA
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Re: Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study Julia Hippisley-Cox, Carol Coupland, Peter Brindle. 357:doi 10.1136/bmj.j2099

Dear Editor

We would like to provide additional information in response to the letter from Professor Osborn and Dr Walters in relation to our recent paper published in the BMJ describing the derivation and validation of QRISK3 [1]. Of the 10,561,100 patients in our QRISK3 derivation and validation cohorts, 593,738 (5.62%) were coded as having severe mental illness. Our definition was based on a combination of the Quality and Outcomes Framework (QOF) definition of severe mental illness plus a subset of the codes from the QOF definition of depression (having excluded those codes indicating mild depression).

Overall across both derivation and validation cohorts, we identified 110,798 patients (1.05% of 10,561,100) with a coded diagnosis of either schizophrenia, bipolar affective disorders or other psychoses, the remaining 482,940 (4.57%) having a coded diagnosis of depression which was either moderate or severe depression or not identified as mild. We based our definition of depression on Read codes indicating moderate or severe depression, for example severe depression, major depression, recurrent depression, psychotic depression, depressive disorder, endogenous depression. We think we should have made this clearer in Box 1 of the original paper.

Overall, across the validation and derivation cohorts, we identified 52,128 patients (0.49% of 10,561,100) who were prescribed atypical antipsychotics at study entry. Of these, 35,452 (68.01%) had a diagnosis of severe mental illness (using the broader definition above) and of these, 24,394 (68.81%) had a diagnosis of bipolar affective disorders or schizophrenia. There were 16,676 (31.99%) of 52,128 patients on atypical antipsychotics, who did not have a recorded diagnosis of schizophrenia, bipolar affective disorders or moderate/severe depression. Most atypical antipsychotic drugs will be initiated in secondary care with the ongoing prescriptions generally issued by primary care.

Stevens et al may have misinterpreted how we calculated the standard deviation of systolic blood pressure so we would like to clarify that. In our Methods section, we stated the following, “To assess variability in systolic blood pressure, we identified all systolic blood pressure values recorded in the five years before study entry and calculated the standard deviation where there were two or more recorded values”. Of those who had a standard deviation calculated, this was based on two values for 33.9% of patients and on three or more values for the remaining 66.1% of patients. So, if there were only two values, these would have been used but if there had been 20 values in the preceding five years for an individual patient, then all 20 would have been used to calculate the standard deviation. In other words, we used all the available values to calculate the standard deviation and in so doing, developed an approach which could be implemented back into the GP computer systems where all such values will be recorded. Regarding the number of imputations, because we calculated variability over 2 or more readings, we feel that 5 imputations remains a pragmatic choice in view of the volume of data (nearly 8 million patients in the derivation cohort). Given the magnitude and significance of the coefficients in our models any imputation variability will have little substantive impact on the precision of estimates and selection of variables based on tests of significance [2].

In our study, we reported an adjusted hazard ratio of 1.08 (95% CI 1.07 to 1.09) in women and 1.11 (1.09 to 1.12) in men associated with a 10-unit increase in standard deviation of systolic blood pressure. This is lower than that reported in the paper by Stevens et al [3] which was 1.18 (95% CI 1.07 to 1.30) but their hazard ratio relates to a standardised measure of systolic blood pressure variability on a different scale to our values (“blood pressure variability divided by its sample standard deviation”). Although Stevens et al undertook a meta-analysis for other outcomes, they were only able to identify a single eligible study for the cardiovascular disease outcome [4]. This study consisted of a highly selected group of 8811 patients with type 2 diabetes recruited to a clinical trial experiencing 404 cardiovascular events who are unlikely to be representative of the general population eligible for cardiovascular disease risk assessment. Their cohort was considerably older (mean age 66 compared with 43 in QRISK3) and had substantially higher systolic blood pressure values compared with the QRISK3 population. For example, the mean systolic blood pressure was 137 mmHg compared with 123 mmHg in women and 129 mmHg in men in our study. Furthermore the blood pressure measurements in the trial were made at specific follow-up times using standardised equipment which does not reflect the situation in a primary care setting where the QRISK3 risk prediction models are intended to be used.

Stevens et al correctly state that patients using antihypertensive medication were included in the cohort of patients used to develop QRISK3. The use of antihypertensive medication in patients with a diagnosis of hypertension was included as a parameter in the risk equation in a similar way to earlier versions of QRISK [5]. Given the purpose of QRISK3 (which is to assess CVD risk at a point in time based on information which is already available), we decided to assess each predictor at baseline based on information that was already available, not on information which might change at a future point. Whilst it would be possible to model changes in medication during follow up as a time varying exposure, it is conceptually difficult to see how such a risk equation could be used in clinical practice as the information would not be known to either the doctor or the patient at the time of assessment. This is also relevant to the interesting point that Peek et al make regarding interventions which may occur during follow-up.

Stevens et al also highlight the similarities in the validation statistics between the models with and without the standard deviation of blood pressure. Whilst we felt that, on average the models had the same overall performance, for those patients that do have higher levels of blood pressure variability, it seemed reasonable to choose the model that could represent that increased risk to some degree. It is possible that the risk associated with blood pressure variability has been underestimated, but choosing a model without any variable for this, would lead to even more underestimation of the true risk in people with variable blood pressure. Further versions of QRISK3 could seek to improve how blood pressure variability is represented in the model.

Lastly, whilst independent external validation of risk assessment tools is the gold standard, numerous validation studies of the QRISK2 cardiovascular risk prediction algorithms (including external studies) have shown that the results in our independent validation practices pretty much match the results when tested in other similar databases both in the UK [6-10] and internationally [11] [12]. We have no reason to think this study should be different but also look forward to future validation studies to confirm our results.

Julia Hippisley-Cox
Carol Coupland
Peter Brindle

References
1. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ 2017;357 doi: 10.1136/bmj.j2099
2. Bodner TE. What Improves with Increased Missing Data Imputations? Structural Equation Modeling: A Multidisciplinary Journal 2008;15(4):651-75. doi: 10.1080/10705510802339072
3. Stevens SL, Wood S, Koshiaris C, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ 2016;354
4. Hata J, Arima H, Rothwell PM, et al. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation 2013;128(12):1325-34. doi: 10.1161/circulationaha.113.002717 [published Online First: 2013/08/09]
5. Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ 2008:bmj.39609.449676.25. doi: 10.1136/bmj.39609.449676.25
6. Collins GS, Altman DG. Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2. BMJ 2012;344:e4181. doi: 10.1136/bmj.e4181
7. Collins GS, Altman DG. An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study. BMJ 2010;340:c2442. doi: 10.1136/bmj.c2442
8. Hippisley-Cox J, Coupland C, Brindle P. The performance of seven QPrediction risk scores in an independent external sample of patients from general practice: a validation study. BMJ Open 2014;4(8):e005809. doi: 10.1136/bmjopen-2014-005809
9. Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Performance of the QRISK cardiovascular risk prediction algorithm in an independent UK sample of patients from general practice: a validation study. Heart 2008;94:34-39. doi: 10.1136/hrt.2007.134890
10. Riley RD, Ensor J, Snell KIE, et al. External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges. BMJ 2016;353 doi: 10.1136/bmj.i3140
11. Arts EEA, Popa C, Den Broeder AA, et al. Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis. Annals of the Rheumatic Diseases 2015;74(4):668-74. doi: 10.1136/annrheumdis-2013-204024
12. Pike MM, Decker PA, Larson NB, et al. Improvement in Cardiovascular Risk Prediction with Electronic Health Records. Journal of Cardiovascular Translational Research 2016:1-9. doi: 10.1007/s12265-016-9687-z

Competing interests: see competing interests for the original paper at bmj.com

19 June 2017
Julia Hippisley-Cox
Professor of Clinical Epidemiology & General Practice; Medical Director ClinRisk Ltd
Carol Coupland and Peter Brindle
Nottingham
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Re: Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons Björn Pasternak, Olof Stephansson, Martin Neovius, et al. 357:doi 10.1136/bmj.j2563

Re: Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons Martina Persson,1,2 Sven Cnattingius,1 Eduardo Villamor,1,3 Jonas Söderling,1 Björn Pasternak,1,4 Olof Stephansson,1,5 Martin Neovius1 doi:10:1136/bmj.j2563 (Persson et al.)

Overweight and obesity have estimated to have caused about 3.4 million deaths worldwide in 2010 (Ng et al). Obesity seriously impacts fetal and neonatal outcomes (Arabin and Stupin). Maternal obesity is often associated with increased risk of adverse health conditions to both mother and fetus (Carmichael, Rasmussen, and Shaw). The best window opportunity to prevent complications associated with maternal obesity is through interventions such as pre-conception assessment and counseling (Iessa and Bérard). Women within the child bearing age should be informed of the importance of having a healthy lifestyle before getting pregnant.

Competing interest: No competing interests

REFERENCES

Arabin, B., and J. H. Stupin. “Overweight and Obesity Before, during and after Pregnancy.” Geburtshilfe und Frauenheilkunde 74.7 (2014): 646–655. PubMed Central. Web.

Carmichael, Suzan L., Sonja A. Rasmussen, and Gary M. Shaw. “Prepregnancy Obesity: A Complex Risk Factor for Selected Birth Defects.” Birth Defects Research. Part A, Clinical and Molecular Teratology 88.10 (2010): 804–810. PubMed. Web.

Iessa, Noha, and Anick Bérard. “Update on Prepregnancy Maternal Obesity: Birth Defects and Childhood Outcomes.” Journal of Pediatric Genetics 4.2 (2015): 71–83. PubMed Central. Web.

Ng, Marie et al. “Global, Regional, and National Prevalence of Overweight and Obesity in Children and Adults during 1980–2013: A Systematic Analysis for the Global Burden of Disease Study 2013.” The Lancet 384.9945 766–781. Web.

Persson, Martina et al. “Risk of Major Congenital Malformations in Relation to Maternal Overweight and Obesity Severity: Cohort Study of 1.2 Million Singletons.” BMJ (2017):j2563. CrossRef. Web.

Competing interests: No competing interests

19 June 2017
Sherneth Heslop Barnett
Registered Nurse, Registered Midwife, Critical Care Nurse.
Sunrise, FL
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Re: Most London hospitals and clinics exceed air pollution limits Pauline Castres, David Dajnak, Melissa Lott, Nick Watts. 357:doi 10.1136/bmj.j2855

I was pleased to see the emphasis on air pollution in a recent BMJ.

As Godlee stated in her Editor's Choice, "the government has devolved most responsibility for delivering its clean air plan to local authorities".

This has long been a problem. Many of the problems of air pollution cannot be solved by local authorities. There may be a pollution blackspot - caused entirely by traffic, over which the local authority has no influence: they have no power over national roads, the location of airports, national policies on the use of different fuel sources, etc.

Quite apart from giving responsibility solely to bodies which have little ability to affect it, this has the secondary effect of ensuring that "instructions" to local authorities cease to be instructions. A significant number of the requirements are placed on local authorities. Daily, they daily have to decide which of their responsibilities they won't attempt to meet (particularly during a period of austerity). One would hope that they will base their decisions on which will do less harm, often when comparing chalk and cheese. Perhaps the decision to use the cheaper cladding for Grenfell Tower was a sensible decision, based on a gamble that a fire wouldn't happen, and the money could be used better elsewhere?

The national government must take overall responsibility for air quality, and be held to account for devolving responsib ility to bodies which are not empowered to make the changes that are necessary if we are to maintain reasonable air quality standards.

Competing interests: No competing interests

19 June 2017
Peter M English
Public Health Physician
N/A - this is a personal response
Epsom
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Re: HIV services are at risk from fragmentation, report warns Anne Gulland. 357:doi 10.1136/bmj.j2001

Brazil is currently moving in the opposite direction from that described by Gulland et al. (1). As a participant in the Fast-Track Project (2) – which aims to increase the number of people living with HIV in antiretroviral treatment, reduce new cases, and reduce mortality, as recommended by the World Health Organization (WHO) – Brazil is implementing measures to enable management of HIV positive patients in primary care.
Since the inception of the current public unified health care system (SUS) in Brazil, primary care has been in a constant process of reorganization (3). Perhaps because of that, HIV care has historically been provided at the secondary or tertiary care levels. This started to change in 2013 (4), when the Ministry of Health established the legal basis for HIV care in the primary setting. This move is of vital importance to our country, and can contribute to both the solidification of primary care and the improvement of patient follow-up – especially considering that institutions do not share an integrated electronic medical record system. Nevertheless, planning of this strategy was insufficient and led to a situation in which unprepared professionals with no HIV experience were asked to handle complex cases.
In order to overcome this problem, our primary care health center – Santa Cecília, affiliated with the Federal University of Rio Grande do Sul (UFRGS) in Porto Alegre, Brazil – created a multidisciplinary space specifically for the care and follow-up of HIV patients. Thus, specialized care is being provided within the primary care setting, with support from nurses, pharmacists, dieticians, and social workers, in addition to a physician specializing in infectious medicine who is available to clarify doubts. Finally, a UFRGS-based telehealth program (TelessaudeRS-UFRGS) (5) provides a toll-free hotline through which primary care professionals can ask questions in real-time. Rapid tests (6) are used for diagnosis, decreasing wait times, and a group of professionals are self-training by routinely reviewing the literature and holding discussion sessions. It should be noted that the incidence of HIV/Aids is high in Porto Alegre: 71.7/100 thousand population in 2015, which corresponds to twice the rate for the state of Rio Grande do Sul (34.7) and more than three times the national incidence (19.1) (7).

Our HIV program was started 2 months ago and, to date, 11 patients (8 males) have been evaluated, with a mean age of 37.2 years. Of these, 5 patients were diagnosed in 2017, and the remaining patients had a diagnosis time between 2 and 30 years. It should be noted that 10 out of 28 patients scheduled so far (including the 11 completed evaluations) did not show up. This high no-show rate (35%) is a sign of the need for active surveillance in the unit, and reflects the numerous barriers we still have to overcome to provide adequate care for this specific population.
We plan to expand our service to include active surveillance, since our region covers a catchment area of approximately 40 thousand, of which about 20% rely on private health insurance. Our planning also includes a focused search for the elderly, who account for about 39.4% of all consultations at our facility in the past 5 years. As national and global estimates show, there is an increase in the number of diagnoses and in HIV mortality in people over 60 years of age.
Finally, we have just started pre-exposure prophylaxis for high-risk patients . We hope that by doing this, and by adopting the strategies that placed HIV care in the UK among the best in the world, we will enhance person-centered care and maintain the movement away from the fragmentation of care.

References
1. Gulland A. HIV services at risk from fragmentation, report warns. BMJ 2017;357:j2001 doi: 10.1136/bmj.j2001.
2. UNAIDS. Get on the Fast-Track. 2016;1-4. http://www.unaids.org/sites/default/files/media_asset/Get-on-the-Fast-Tr...
3. Campos. CEA. A organização dos serviços de Atenção Primária à Saúde no Brasil. Rev Bras Med Fam e Com. 2006;3(6):131–47.
4. Brazil. Portaria Conjunta No. 1. January 2013. 2013;53(9):1689–99. http://www.aids.gov.br/sites/default/files/anexos/legislacao/2013/52759/...
5. Harzheim E, Gonçalves MR, Umpierre RN, et al. Telehealth in Rio Grande do Sul, Brazil: bridging the gaps. Telemed J E Health. 2016;22(11):938-44.
6. Brazil. Portaria No. 29. December 2013. 2013;2–3. http://www.aids.gov.br/sites/default/files/anexos/legislacao/2014/56078/...
7. Prefeitura de Porto Alegre. Público pode fazer exames gratuitos de HIV no Largo Glênio Peres. June 2017. http://www2.portoalegre.rs.gov.br/sms/default.php?p_noticia=999190672&PU...

Competing interests: No competing interests

18 June 2017
Juliana Nunes Pfeil
Family Physician
Kizzy Ludnila Corezola, Cynthia Goulart Molina-Bastos, Patricia Sampaio Chueiri, Marcelo Rodrigues Gonçalves
TelessaudeRS-UFRGS
Rua Mostardeiro, 366
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Re: What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour? Sara Kenyon, Julia Sanders, Lee Middleton, Tracey Johnston. 357:doi 10.1136/bmj.j2469

The authors pose the question - What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour? and state in their paper that "There is no consensus on the optimal dose regimen of oxytocin for delay in the first stage of labour in nulliparous women at term (37-42 weeks’ gestation) to reduce unplanned caesarean section and increase vaginal birth with minimal adverse events". However, they describe only low and high dose oxytocin regimens and fail to acknowledge that no oxytocin at all is associated with a spontaneous delivery just as often as when oxytocin is given (1,2) or that discontinuation of oxytocin once the active phase of labour is reached can result in higher spontaneous delivery rates than continuing oxytocin (3,4). The paper in its list of trials (box 2) only describes those addressing high and low dose oxytocin, which implies that these are the only options for addressing an improvement in the mode of delivery in slow labour. Although oxytocin shortens labour, it does so at the expense of an increase in uterine hyperstimulation and abnormal fetal heart rate patterns, and this may not be to the advantage of either the woman or her baby. Avoiding oxytocin use may be preferable because of the high proportion of litigated cases of adverse outcome associated with its use (5). We anticipate that our current on-going trial of stopping oxytocin at 6 cm of cervical dilatation following induction of labour will strengthen the evidence for limiting (not increasing) the use of oxytocin (6).

Yours sincerely,

Sidsel Boie, MD, Department of Obstetrics and Gynecology, Randers Regional Hospital, Denmark
Julie Glavind, MD, PhD, Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark
Niels Uldbjerg, Professor, DMSc, MD, Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark
Pinar Bor, Associate professor, MD, PhD, Department of Obstetrics and Gynecology, Randers Regional Hospital, Denmark
Philip Steer, Emeritus Professor, BSc, MD, FRCOG, Imperial College London

(1) Wei S, Wo BL, Qi HP, Xu H, Luo ZC, Roy C, Fraser WD. Cochrane Database Syst Rev. 2013 Aug 7;(8):CD006794. doi: 10.1002/14651858.CD006794.pub4
(2) Bugg GJ, Siddiqui F, Thornton JG. Cochrane Database Syst Rev. 2013 Jun 23;(6):CD007123. doi: 10.1002/14651858.CD007123.pub3)
(3) Vlachos DE, Pergialiotis V, Papantoniou N, Trompoukis S, Vlachos GD. J Matern Fetal Neonatal Med. 2015;28(12):1421-7.
(4) Bor P, Ledertoug S, Boie S, Knoblauch NO, Stornes I. BJOG. 2016;123(1):129-35
(5) Berglund S, Grunewald C, Pettersson H, Cnattingius S. BJOG 2008; 115(3):316-323.
(6) https://clinicaltrials.gov/ct2/show/NCT02553226

Competing interests: No competing interests

18 June 2017
Sidsel Boie
MD
Julie Glavind, MD, PhD Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark; Niels Uldbjerg, DMSc, MD Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark; Pinar Bor, Associate professor, MD, PhD, Department of Obstetrics and Gynecology, Randers Regional Hospital, Denmark; Philip Steer, Emeritus Professor, BSc, MD, FRCOG, Imperial College London
Randers Regional Hospital
Skovlyvej 1, 8930 Randers NØ, Denmark
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Re: Half of salaried and locum GPs are stressed, BMA survey finds Abi Rimmer. 357:doi 10.1136/bmj.j2943

I do not deny that many GPs are stressed but how is it possible to draw any useful conclusion from a survey which has a 15% response rate? It seems extremely unlikely that responders are going to be a representative sample and one might say that the 85% who did not respond and half of those who did (i.e. a total of 92.5%) of salaried and locum GPs did not report stress when given the opportunity to do so.
The BMA should be setting an example when it comes to presenting data and not generating unjustifiable but eye catching conclusions in a way which we commonly see and criticise in the mainstream media.

Competing interests: No competing interests

18 June 2017
Paul M van den Bosch
Salaried GP
College Road Surgery, Woking
College Road Surgery, Woking
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Re: Coroner calls for GPs to be allowed to order urgent CT scans after patient death Clare Dyer. 357:doi 10.1136/bmj.j2815

I applaud the coroner for shining a light on this issue, but the problem is wider than she has identified.
The issue is that patients in the UK are unable to access urgent CT scans, regardless of who has referred them. Patients in many areas are currently waiting more than a month for an "urgent" CT scan.
The UK's lamentable failure to invest appropriately in diagnostic imaging services - equipment and people - is now coming home to roost in the shape of poorer outcomes for patients with cancer as well as impaired patient flow in the acute sector.
Policy-makers and commissioners of services must be persuaded that CT is not an expensive luxury but a fundamental pillar of medical diagnosis. Who would have thought that it would still be necessary to point that out in 2017?

Competing interests: No competing interests

18 June 2017
Giles Maskell
consultant radiologist
Royal Cornwall Hospital, Truro
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Re: Do doctors have a duty to take part in pragmatic randomised trials? Marion K Campbell, Charles Weijer, Cory E Goldstein, Sarah J L Edwards. 357:doi 10.1136/bmj.j2817

Do 'patients' have a duty to take part in pragmatic randomised trials?
At the very least patients receiving essentially free medical care from universal health coverage medical systems?
For their very own sake and for the others...

Competing interests: No competing interests

18 June 2017
Carlos Guijarro
MD Internal Medicine
Hospital Universitario Fundacion Alcorcon. Universidad Rey Juan Carlos
Budapest 1
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Re: Stress at work Thomas Despréaux, Olivier Saint-Lary, Florence Danzin, Alexis Descatha. 357:doi 10.1136/bmj.j2489

This is a great resource which clearly sets out a practical framework to deal with the thorny issue of workplace stress. It ought to be of great value to any doctor who sees working age patients.

While stress can't be avoided, workplace stress causes a great deal of morbidity and lost working time.

Competing interests: No competing interests

18 June 2017
Davi Poots
Consultant Occupational Physician
Dr
50 Stroan Road
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