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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 Editor,

I read with interest this interesting study and the commend the authors for their detailed work. However, I do feel ultimately the conclusions are wrongheaded. Firstly, and most importantly, it is impossible to account for the underlying indication for the steroids, and there will be clear confounding by indication. Despite the apparent matching, clearly patients prescribed steroids for URTI are much more likely to have underlying COPD or asthma, and so this is not a true comparison. It is also clear from the demographic group that these patients are older, and more comorbid.

Secondly, there doesn't appear to be a clear mechanism for short term steroids causing any of these conditions outside sepsis, which the authors accept, although there is a clear mechanism from the underlying condition (i.e. fall due to pain from arthritis, confusion from LRTI). Again, it would seem silly to attribute this to the steroids without any clear mechanism.

Thirdly, if we really felt steroids were the cause of these adverse events, we would expect a dose-response relationship, which is clearly not evident from these results.

Finally, even if we feel the above hypotheses to be true, the numbers needed to harm are very high: using the web appendix to calculate numbers needed to harm (NNH): I calculate NNHs for most adverse events to be in the high hundreds or thousands. Steroid use is clearly common, so even high NNHs are important, but given the huge confounding by indication, the NNH are likely to be even higher in the real world.

In summary, I'm not convinced there is any strong theoretical evidence supporting steroid use causing any of these adverse events except sepsis, where the NNH is 5000. There is no dose response relationship evident, and there is clearly strong confounding by indication in this study, which makes the results difficult to interpret with any certainty.

I'd struggle to not prescribe steroids to patients with an exacerbation of COPD (NNT 9 to prevent treatment failure, from a Cochrane review (1)) based on this very limited evidence.

Many thanks

1) http://www.cochrane.org/CD001288/AIRWAYS_do-systemic-corticosteroids-imp...

Competing interests: No competing interests

13 April 2017
Fergus W Hamilton
Medical Trainee
Weston Area Health Trust
Weston General Hospital, W-S-M, BS23 4TQ
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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

In the bad old days, before portfolio GPs were born, when sports injuries, bleeding noses, ingrowing toe nails, boils on bums, and childrens’ ‘pulled elbows’ made life interesting and satisfying for we (now ageing) simpletons, the occasional bleeding tooth socket would usually respond magically and quickly to a homeopathic remedy like arnica or phosphorus. Nowadays all must all be redirected to ENT, A&E, podiatry, surgery or orthopaedics. Even back to the dentist.

Little wonder that GPs wish to retire from the creaking NHS in early middle age.

Competing interests: No competing interests

13 April 2017
Noel Thomas
retd/ part time GP
BronyGarn, Maesteg, Wales CF34 9AL
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Re: Electrical injury Victor Waldmann, Kumar Narayanan, Nicolas Combes, Eloi Marijon. 357:doi 10.1136/bmj.j1418

This article, featured on the front cover of the BMJ as 'Managing Electrical Injury', hardly does what it says on the tin. Whilst the authors provide a hint of the potential complexity of the problems associated with the passage of electrical injury injury through the human body, they virtually dismiss the management as "mainly symptomatic". That is to ignore a whole host of problems which should be dealt with not by awaiting symptoms, but by the experienced clinician anticipating problems.

For example, a problem not often appreciated in the case of the "finger skin burns" illustrated at fig. 2A, is that such burns may be far more than skin only, with a deep underlying column of injured tissue which if not addressed will persist and often become infected over many weeks. Or that the 'severe foot burn' seen in fig 2B may represent the exit/entry burn of a high tension current which has also caused un-appreciated bone and muscle heating leading to very severe secondary effects such as haemolysis, rhabdomyolysis, and compartment syndrome with secondary circulatory occlusion to the extremity. These must all be dealt with ahead of symptoms by protecting renal circulation, fasciotomies and possibly massive tissue debridement.

Setting aside the fact that it is quite simply unfair on readers to suggest that the management of electrical injuries can be usefully covered in three pages, the generalist will rightly ask questions such as "when can I allow a patient to be unsupervised after suffering an electric shock?", "when might there be complications ahead?", "what is the difference between low and high tension electrical injury", and "when should I involve a specialist?". These questions are neither asked nor answered in the article and to perfectly fair to the authors, perhaps the BMJ should instead have entitled the piece as "A brief review of the possible effects of electric shock" to avoid encouraging readers into thinking they might pick up practical management points in this field.

Competing interests: No competing interests

13 April 2017
Peter J Mahaffey
Consultant Plastic & Reconstructive Surgeon
Bedford
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Re: Regulator takes action against four online pharmacies Matt Limb. 357:doi 10.1136/bmj.j1784

I was disappointed to read the description of the suspension of the registration of online pharmacy company, Doctor Matt. It frames "as little as 17 seconds" for the issuing of a prescription as some great scandal. But, as was ably pointed out by one of its GPs on Radio 4's Today Show, this was a repeat prescription for a patient where nothing had changed since the issuing of last prescription. More pertinently, this 17 seconds is approximately 16 seconds more than a GP at their end of their morning clinic spends reviewing a patient's records when signing the bundle of repeat prescriptions . I expect better than this lazy, sensationalist journalism from the BMJ.

Competing interests: No competing interests

13 April 2017
Daniel J Kearns
ST1 Radiology
Oxford
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Re: The role of the microbiome in human health and disease: an introduction for clinicians Vincent B Young. 356:doi 10.1136/bmj.j831

Even brief periods of antibiotic use that disturb gut microbiome are associated with later increases of colorectal adenomas, which, in time, could transform into invasive colon cancers.
Reference
http://gut.bmj.com/content/gutjnl/early/2017/03/16/gutjnl-2016-313413.fu...

Competing interests: No competing interests

13 April 2017
Stavros Saripanidis
Consultant in Obstetrics and Gynaecology
Thessaloniki, Greece
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Re: Prognosis of undiagnosed chest pain: linked electronic health record cohort study Spiros Denaxas, Arturo González-Izquierdo, Richard A Hayward, Pablo Perel, et al. 357:doi 10.1136/bmj.j1194

Providing patients with a timely and correct diagnosis poses significant challenges to frontline physicians, and this is no better exemplified than in those presenting with acute chest pain. As Jordan and colleagues have highlighted, a history of classical anginal symptoms remains an excellent discriminator for identifying individuals at high-risk of myocardial infarction, yet in primary care these account for only a minority of cases (<5%). [1] The main focus of acute chest pain management over the past decade has been to identify prognostically significant coronary artery disease (CAD) in those with less specific symptoms, and notably these cases accounted for over 70% of index presentations in the CALIBER study. However, an unresolved question is how to select out the high-risk individuals in these overall low-risk populations.

In this real-world registry, a referral for a specialist opinion or requesting a cardiac investigation was often considered unnecessary by generalists when faced with unattributed chest pain presentations, even at 6 months following presentation. Of note, we would be interested to know why exercise ECG was not considered as an investigation of chest pain, especially as this was the first line investigation of choice for stable chest pain during the time frame of this study. [2]

It would also be useful to know the composite breakdown of the different investigations in the current study to allow the results to be considered in relation to current practice where imaging has assumed a far more significant role in modern guidelines. Whilst cardiovascular computed tomography (CT) was rarely used prior to the NICE CG95 guidelines published in 2010, [3] contemporary trials in non-invasive cardiac imaging (such as SCOT-HEART [4]) have demonstrated that CT coronary angiography (CTCA) improves the diagnostic certainty of CAD in patients with less specific symptoms of angina. In CALIBER only 9.9% of unattributed cases underwent early investigation within 6-months, but similar to SCOT-HEART, prescription of statins increased when investigation results were available to frontline clinicians.

Importantly, the 2016 update of the NICE CG95 guidelines now recommend CTCA as the first line investigation in the assessment of undifferentiated chest pain. In addition, CTCA is the only testing strategy that has been shown to reduce ‘hard’ cardiovascular outcomes through more appropriate prescribing of preventive therapy. [5] Rapid confirmation or exclusion of CAD with CTCA allows appropriate reassurance or instigation of primary prevention therapy. Additionally, assessment of the wide-field-of-view dataset on CTCA studies may potentially allow for detection of other non-cardiac pathology mentioned in the CALIBER study, such as hiatus hernia, lung pathology and spinal abnormalities. With modern CT scanners, the average radiation dose from CTCA in the UK is now equivalent to a year or less of background radiation. [6] Its increased use in the assessment of chest pain in primary care may reduce morbidity and mortality as demonstrated already in secondary care based studies such as SCOT-HEART.

References

[1] Jordan KP, Timmis A, Croft P, et al. Prognosis of undiagnosed chest pain: linked electronic health record cohort study. BMJ 2017;357;j1194.

[2] de Bono D. Investigation and management of stable angina: revised guidelines 1998. Joint Working Party of the British Cardiac Society and Royal College of Physicians of London. Heart 1999;81:546-55.

[3] National Institute for Health and Clinical Excellence. Chest pain of recent onset: Assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. CG95. London: National Institute for Health and Clinical Excellence, 2010.

[4] SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary artery disease (SCOT-HEART): an open-label, parallel group multicentre trial. Lancet 2015;285:2383-2391.

[5] Williams MC, Hunter A, Shah AS, et al. Use of coronary computed tomographic angiography to guide management of patients with coronary disease. J Am Coll Cardiol 2016;67:1759-1768.

6. Nicol E, Castellano I, Harden S. A National survey of coronary CT angiography doses in the UK on behalf of the British Society of Cardiovascular CT (BSCCT). J Cardiovasc Comput Tomogr 2016;10:S60.

Alastair J Moss
Clinical research fellow, University of Edinburgh

Jonathan R Weir-McCall
Clinical lecturer and radiology registrar, University of Dundee

Michelle C Williams
Clinical lecturer and radiology registrar, University of Edinburgh

Edward D Nicol
Consultant cardiologist, Royal Brompton Hospital and Harefield NHS Trust, London

Competing interests: No competing interests

13 April 2017
Alastair J Moss
Wellcome Trust clinical research fellow
University of Edinburgh
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh UK
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Re: Coca-Cola’s secret influence on medical and science journalists Paul Thacker. 357:doi 10.1136/bmj.j1638

We are extremely disappointed by the lack of facts and truth in freelance reporter Mr. Thacker’s recent article in The BMJ.
The report relied upon selective use of “evidence” and contained numerous errors of omission to manufacture a conspiracy theory about events that took place many years ago.

The article was correct in that we did accept some funding from Coca-Cola, and others, to put on educational events for reporters. We did so with the understanding that the drink-maker would have absolutely no say in the program content. Funding by Coke or any other private business has never influenced our research or educational activities. We also agree with Mr. Thacker that comprehensive disclosure of funding sources is important. We are now taking even greater steps to be upfront and clear about our funding sources, to ensure that the focus is on quality science and education.

Mr. Thacker introduces his “secret influence” theory by insinuating that we promote physical inactivity as the cause of obesity and downplay diet, which would help minimize any role of sugary beverages. Despite this foundational allegation, he provides no factual evidence of this. We have authored hundreds of peer reviewed research papers, reviews and chapters on obesity and have never promoted such a message. There is clear scientific evidence showing that sugar-sweetened beverages and many other diet factors contribute to obesity. There is also clear evidence that sedentariness, lack of physical activity, and poor sleep patterns contribute to obesity. These workshops addressed a broad range of lifestyle and other factors that contribute to obesity, including diet, exercise, sleep, stress, and the environment.

Mr. Thacker’s carefully constructed story line suggests that Coke initiated this plot to influence journalists to write stories favorable to Coke in order to take pressure off the sugary drink business. In fact, the idea for these conferences came from us. One mission of our NIH-funded Nutrition Obesity Research Center (NORC) is to educate the public about obesity. Because health reporters frequently contact us seeking information and comment about obesity and its many causes, treatments and strategies for prevention, we saw the need to offer journalists a more in depth look at obesity. The National Press Foundation was enthusiastic when we approached them about the concept and, when asked, journalists also said this was a great idea. The idea of engaging journalists in a more in depth forum to talk about a global problem was modeled after the annual journalism events (Age Boom Academy) begun in 2000, hosted by the Robert N. Butler Columbia Aging Center. Their purpose was to educate journalists about how the increase in average lifespan presents a multi-faceted problem with health, social and economic implications. Obesity represents a similar multi-faceted problem.

Mr. Thacker implied that content delivered at the conferences was biased in favor of Coca Cola, yet, he did not provide any support for this contention. He cited a panel including executives from Coke and McDonalds as evidence of bias, although reporters had actually asked to have such company representatives on the program since they normally do not get access to such high-level executives. As evidence that these events worked to influence reporters’ stories he cites an article by a CNN reporter who attended one of the events, titled “Soda makers want to cut calories, but is diet really better?” The article actually emphases the role of sugary sodas in contributing to obesity and discusses whether diet sodas can help with the obesity epidemic, concluding that the jury is still out and there are persistent doubts about their effectiveness.

The CNN report made no mention of physical activity and provided no favorable portrayal of Coke or its products. It is difficult to see how this article is evidence of the alleged conspiracy having its intended effect. Mr. Thacker also suggests there was an article from one of the journalists saying that physical activity was more important than diet in obesity. He did not refer this article because, to our knowledge, there was no such article. More than 40 journalists attended the events we hosted and dozens of stories appeared after each, yet he rests his case on one published article that is actually not favorable to Coke and another for which there is no reference. It would seem that Mr. Thacker’s serious allegations of “secret influence” must somehow be supported by, “secret evidence”.

The one reporter cited by Mr. Thacker as having a concern about the partial funding by Coke actually said in her review of the program: “I would have appreciated some more clarity up front on the funding of the program. I don't know that it would have made a difference for me that it was funded by Coca-Cola, but I think some more transparency on that would have been good.” She added: “Overall, it was also very well organized (not easy!!), and was a great introduction for me to the current science on obesity and the policy debates. It gave me good ideas for stories, and lots of avenues for follow-up.”

Also not mentioned in Mr. Thacker’s article is the fact that all three conferences were highly rated by journalists based on evaluations administered by the National Press Foundation. The report of the 2014 meeting was released through a Freedom of Information Act request and can be seen here (1). Reports of the earlier meetings are available by request (2), so anyone can judge whether they paint a picture of scientific bias aimed at convincing journalists that sugary soda is not a problem for obesity, or if the evidence is more consistent with the National Press Foundation delivering outstanding workshops that helped journalists better understand the multi-faceted problem of obesity.

It seems that articles like this are no longer investigative journalism at its best and are truly story-telling for the purpose of supporting a personal point of view, or the point of view by advocates pushing a specific cause. I would only hope that readers and editors of BMJ would look at this with a critical eye, especially as medical professionals and scientists, and challenge the “evidence” used to support the author’s opinion.

(1) https://drjameshill.files.wordpress.com/2017/04/final-report-obesity-201...
(2) James.hill@ucdenver.edu

Competing interests: Drs. Peters and Hill worked with the National Press Foundation to host the journalist conferences referenced in the article. Funding for these conferences came from unrestricted educational gifts from a variety of donors, including the Coca-Cola Company.

13 April 2017
John C. Peters
Professor of Medicine
James O. Hill, Professor of Pediatrics
University of Colorado
12348 E. Montview Blvd., Aurora, CO 80045 USA
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Re: Rosamund Snow David Payne. 346:doi 10.1136/bmj.j850

Pathway was lucky to work with Rosamund on a WYPIT article last year, written by one of our volunteers, a formerly homeless man.

Homeless patients often feel unwanted or unreached by the healthcare profession. Being given a chance to write for a publication as well regarded at the BMJ was an incredibly proud moment for our team, and Rosamund supported our writer Ian through every step of the journey, building his confidence. He has since gone on to address medical conferences, and write for other news outlets, taking flight in a new career.

This tiny piece of work with Rosamund seems to encapsulate everything I knew about her. She championed an unheard voice, emphasised the importance of patient engagement and was not afraid to help us raise an opinion which might be controversial. Her compassion and dedication were immutable, and the articles she helped to produce are a fitting legacy to those qualities.

At a personal level, when I met Rosamund she was instantly someone I wanted to know better, on a human level as well as a professional one. I am sad that we will never have that chance, and I hope that all of those who did know her will cherish their memories together.

Competing interests: No competing interests

13 April 2017
Cat Whitehouse
Communication and Administration Officer
Pathway, the Homeless Healthcare Charity
5th Floor East, 250 Euston Road, London, NW1 2PG
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Re: Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study Henrik Toft Sørensen, Liam Smeeth, Laurie A Tomlinson, et al. 356:doi 10.1136/bmj.j791

REFERENCES:
1. Journal of the American College of Cardiology
Volume 66, Issue 11, September 2015
DOI: 10.1016/j.jacc.2015.07.021
PDF Article
Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks Versus Whites
Gbenga Ogedegbe, Nirav R. Shah, Christopher Phillips, Keith Goldfeld, Jason Roy, Yu Guo, Joyce Gyamfi, Christopher Torgersen, Louis Capponi, Sripal Bangalore

Competing interests: No competing interests

13 April 2017
Jose Mario de Oliveira
Associate Profressor of Medicine
Department of Medicine-Universidade Federal Fluminense
Rua Senador Vergueiro # 2 Apt. 202. Flamengo. Rio de Janeiro, RJ, Brazil.
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Re: Cost effective but unaffordable: an emerging challenge for health systems Benedict Rumbold, Albert Weale, James Wilson, Annette Rid, et al. 356:doi 10.1136/bmj.j1402

NICE’s Carole Longson suggests that our recent editorial on NICE’s new affordability test indicates that we “have misunderstood its primary purpose” [1]. We beg to differ. We are acutely aware of the need to minimise costs to the NHS, as the recent update to the Five Year Forward View underlined [2]. The crisis facing the NHS requires more—not less—debate about how NICE and NHS England (NHSE) should address the challenge of drug cost inflation.

In its response, NICE seeks to downplay the significance of the new budget impact test [1]. In addition to affecting only a “minority of drugs”, the test will apparently lead to only minimal delays, as price negotiations will begin “well before” appraisals and “be completed by the time NICE publishes its guidance” [1]. If this is the case, why is the new budget impact test needed at all? NICE can already waive the 90-day funding requirement if it considers that the recommended technology “cannot be appropriately administered until other appropriate health services resources […] are in place” [1].

NICE argues that the new test does not seek to delay access to cost-effective technologies, but aims to trigger price negotiations with industry [1]. Stephen Duckett rightly points out that if this frees up money to be spent gainfully elsewhere, it may be ethically justified [3]. However, the ethical imperative to minimise costs exists for all technologies, not just those costing more than £20 million a year. In addition, the Pharmaceutical Price Regulation Scheme (PPRS) already guarantees the Government a rebate when its annual cap for drug spending has been reached—a routine event in recent years [4]. It would be a shame if upfront price discounts simply replace the existing PPRS repayment, leading to a small cash flow advantage but no actual cost reduction.

Greg Fell questions the fairness of how NICE and NHSE currently judge value for money for health services [5]. We believe that NICE’s “ethics of opportunity costs” framework is generally fair [6]. However, the new budget impact test increases rather than reduces unfairness, particularly if access to some technologies is “phased in” gradually as NICE suggests [1], raising the prospect of inequities arising not just between patient groups but also within them. It is important that this debate on affordability continues to ensure that the NHS achieves maximum value for the money it spends on drugs [7].

Acknowledgments:
With thanks to Catherine Max for her contributions to both the original article and this response.

References:
1. Longson, C. Re: Cost effective but unaffordable: an emerging challenge for health systems. BMJ 2017;356:j1402.
2. NHS England. Next steps on the NHS five year forward view: NHS England, March 2017. https://www.england.nhs.uk/wp-content/uploads/2017/03/NEXT-STEPS-ON-THE-...
3. Duckett, S. Re: Cost effective but unaffordable: an emerging challenge for health systems. BMJ 2017;356:j1402.
4. Ward A and Neville S. ‘Pharma groups to pay NHS £550m ‘rebate’’. Financial Times, December 23 2015. https://www.ft.com/content/6c34f7de-a966-11e5-843e-626928909745
5. Fell G. Re: Cost effective but unaffordable: an emerging challenge for health systems. BMJ 2017;356:j1402.
6. Rid A, Littlejohns P, Wilson J, et al. The importance of being NICE. Journal of the Royal Society of Medicine 2015;108(10):385-89. doi: 10.1177/0141076815598877
7. Charlton V, Littlejohns P, Rid A, et al. Cost effective but unaffordable: an emerging challenge for health systems. BMJ 2017;356:j1402.

Competing interests: No competing interests

13 April 2017
Victoria Charlton
PhD student
Peter Littlejohns, Katharina Kieslich, Polly Mitchell, Benedict Rumbold, Albert Weale, James Wilson and Annette Rid (corresponding author)
Department of Global Health and Social Medicine, King's College London
Room 2.11, East Wing, Strand Campus King's College, London Strand London WC2R 2LS
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