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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: David Oliver: What GPs told me about how they see the future David Oliver. 358:doi 10.1136/bmj.j3976

Dear David
Thank you for trying to explore how GPs see the future. Something those of us who seek to represent GPs grapple with regularly.
Your question is as useful as asking 'how do hospital doctors see their future'. Not useless but of limited use. A geriatrician and an intensive care doctor may have differing views but they will be valid in the context that they work.. Those providing primary care to different populations need their specific views heard and heeded. Reductionist analysis leads to a number of erroneous over-simplistic conclusions in your piece. You are in good company though - a House of Lords committee managed this too!!
On a positive note you got one thing right - 'a one size fits all model' is pointless. As pointless as it would be to put all surgeons/physicians/anaesthetists/obstetricians/paediatricians/etc in the same basket simply because they typically work in a hospital.

Competing interests: No competing interests

15 September 2017
A. Drummond Begg
Re: Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials Klaas M Huijbregts, Anton J L M van Balkom, et al. 358:doi 10.1136/bmj.j3927

I would like to thank the authors for trying to help clinicians who are responsible for long term prescribing of drugs. Whenever a drug is prescribed both patient and doctor should ask the question what are the long term benefits and harms. Deprescribing is as important as prescribing to reduce the risks of unnecessary polypharmacy.
Unfortunately the meta-analysis doesn't appear to analyse long term all cause harms. People (formerly known as patients) would rather have a single n1000 trial looking at all cause harm vs benefit over a much longer period. Trial should not be performed by a drug company with a vested interest in outcomes. We then need better data on the long term benefits and all cause harms of non-drug treatments to provide people with more meaningful choices. Better primary research rather than more meta-analysis please.

Competing interests: No competing interests

15 September 2017
A. Drummond Begg
Re: No overall increase in all cause mortality with HRT, study finds Jacqui Wise. 358:doi 10.1136/bmj.j4230

Epidemiological studies can seriously mislead if epidemiologists do not have clean never users of hormones for controls. Their resulting data can encourage false claims of benefit or no effect .1

How many deaths would there been if the Women's Health Initiative Studies, of either combined progestogen HRT or estrogen only HRT, had not been terminated prematurely? This was because of unacceptable increases in cancers and vascular diseases? Most women enrolled had previously used progestogens and oestrogens for either contraception or therapy but nevertheless, the WHI epidemiologists randomly divided the women into Takers or Never takers.

In reality, the world-wide fall in hormone use after the early WHI terminations resulted in decreases in breast and ovarian cancer incidence and mortality. 2-5

Use of HRT progestogens and oestrogens quickly increases the main causes of death. It is a shame to encourage use of carcinogenic, vasoactive, psychoactive and immune modulating hormones merely to suppress vasomotor symptoms. As a clinician, I have found avoiding smoking and alcohol, low allergy high protein diets, repletion of essential nutrients to be safe and basic .6,7 There are more details in my lectures at

1 No overall increase in all cause mortality with HRT, study finds. BMJ 2017;358:j4230

2 Grant ECG. Reduction in mortality from breast cancer: fall in use of hormones could have reduced breast cancer mortality. BMJ. 2005 Apr 30;330(7498):1024.

3 Colditz GA. Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin. Breast Cancer Res. 2007;9:108.

4 Ravdin M, Cronin KA, Howlander N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA. The Decrease in Breast Cancer Incidence in 2003 in the United States.NEJM. Vol. 356, No.16. April 19, 2007

5 Grant Ellen C G. Endometrial cancer with progestagen and oestrogen oral contraceptives. The Lancet Oncology, 2015;16: 15,e527

6 Grant ECG. Food allergies and migraine. Lancet 1979;1:966-6.

7 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity , and mineral imbalance .J Nutr Environ Med 1998;8:105-116.

Competing interests: No competing interests

15 September 2017
Ellen C Grant
Physician and medical gynaecologist
Kingston-upon-Thames, UK
Re: Substance misuse in older people Rahul Rao, Ann Roche. 358:doi 10.1136/bmj.j3885

Substance misuse is not simply a risk to the health of older people but a risk factor for elder abuse and neglect. The older person who may be unable to care for him/herself and reliant on others may become increasingly neglectful of their person, their relationships and surroundings, becoming 'easy prey' to those who take advantage of them. But so too can other people's substance misuse negatively affect older people - whether they are family members, care home residents or neighbours. In community and long-term care settings the misuse of substances by a minority of people 'caring' for older people has been shown to impact on their care and treatment, and ultimately on their wellbeing. For care services, the role of taking up references and checking on staff provides some valued monitoring. Health professionals can act as the 'eyes and ears' of safeguarding when meeting with older people who may be at risk of harm from their own or others' substance misuse.

Competing interests: No competing interests

15 September 2017
Jill T Manthorpe
Professor of Social Work
Re: Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study Sana R Mostaghim, Joshua J Gagne, Aaron S Kesselheim. 358:doi 10.1136/bmj.j3837

It is good to read the research article “Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study”.

Expedited approvals for new drugs include, “Accelerated approval pathway”, “Breakthrough therapy”, “Fast track designation”, and “Priority review”. The Food and Drug Administration (FDA) initiated “Accelerated approval regulations” in 1992, and the Federal Food, Drug, and Cosmetic Act (FD&C Act) in 2012 allowed the FDA "Accelerated approval for the drugs for serious conditions" with an unmet medical need, based on a surrogate marker or an intermediate clinical endpoint; it also included “Breakthrough therapy”[1,2]. FDA designed a “Fast track process” to facilitate the development, & a “priority review” for faster review within six months (compared to 10 months under standard review) [3,4].

Drug companies must conduct a “confirmatory trial” once the drug is on the market in an accelerated approval program and the FDA must take appropriate action regarding its approval if the drug’s safety or efficacy results are questionable [5].

Post-approval studies seldom cover the "deficit of knowledge" (orphan drugs) [6]. FDA in their letters generally do not approve applications for new drugs for reasons related to safety and efficacy deficiencies [7]. Fast-track drugs approval by the FDA is harmful and not good for the public at large, the reason being that drug companies are paying huge sums to fast-track FDA approval [8].

Evidence based medicine appears to be broken owing to corruption in clinical research and also to overdiagnosis harming the patients & healthy people [9,10].

Big pharma companies seem to increase the costs of drugs owing to commercial & professional vested interests and health system incentives favouring more tests and treatments [11].

It is not just the responsibility of regulatory bodies at a high level: responsibility starts with "Investgators who are involved in the study" and “Institutional Ethics Committees” /or “Institutional Review Boards”, which have a major role in approving the projects/RCTs. Responsibility also lies with "Sponsors/ Funders" of the projects/RCTs.

The FDA should take appropriate measures to prevent the misuse of "Expedited regulatory pathways" for the safety of patients at large. Thank you for an interesting and a relevant research article.


5. BMJ 2015;351:h5260

Competing interests: No competing interests

15 September 2017
Dr. Rajiv Kumar
Dr. Sangeeta Bhanwra, Dr. Jagjit Singh, Faculty, Dept. of Pharmacology, Government Medical College & Hospital, Chandigarh, India.
Dept. of Pharmacology, Government Medical College & Hospital Chandigarh 160030. India.
Chandigarh, India
Re: Autopsy results confirm 4 year old Italian girl died from malaria Michael Day. 358:doi 10.1136/bmj.j4235

Malaria is re-established in many Regions in neighboring Greece. [1][2]
If this Italian girl had previously been for summer vacations in Greece she could have been infected there.

Competing interests: No competing interests

15 September 2017
Stavros Saripanidis
Consultant in Obstetrics and Gynecology
Re: Should Google offer an online screening test for depression? Ken Duckworth, Simon Gilbody. 358:doi 10.1136/bmj.j4144

If online screening with the PHQ-9 test detects depressive traits, patients should be reminded that CBT or Behavioural Activation effectively treat clinical depression.
A meta-analysis published in the British Journal of Psychiatry has found that even patients with the most severe depression can expect to get as much benefit from cognitive behavioural therapy (CBT) as those with less severe symptoms. [1]
Even junior MHWs, trained for only 5 days, were able to deliver Behavioural Activation sessions against Depression, with equally effective outcomes, compared to CBT or second generation antidepressant pharmacotherapies, without side effects. [2][3]
Google (Alphabet Inc) could subsequently offer free peer-reviewed online computerized CBT AI sessions.

Competing interests: No competing interests

15 September 2017
Stavros Saripanidis
Consultant in Obstetrics and Gynecology
Re: Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies Konstantinos K Tsilidis, John PA Ioannidis, Harry Campbell, Evropi Theodoratou, et al. 357:doi 10.1136/bmj.j2376

Dear Sir,

Very recently Xi and co-workers published a huge review on any possible relationship between serum uric acid and several clinical conditions involving also the cardio-renal and metabolic systems. They conclude that an indisputable causative role for uric acid can be established only for gout while all the other evidence should be considered with caution. I basically agree with this conclusion since there is no doubt that hyper-uricemia and gout are strictly related, but I am not so convinced that the interpretation of the possible effects of uric acid beyond gout can be explained by using the plasma levels as discriminatory tool.

In particular the same serum level of uric acid can be found in patients bearing to a completely different pathophysiological pathway since serum uric acid is the final result of the balance between production and excretion.

Second, those who are affected by a condition of overproduction of uric acid usually have some functional over expression of xanthine-oxidase and associated oxidative strass that can selectively contribute to the cardio-renal and metabolic settings. The identification of these subjects will be a mandatory goal for the near future since they will probably be the target of cardiovascular prevention by xanthine-oxidase inhibitors.

Third, the studies of Mendelian randomisation included in the manuscript are focused exclusively on the importance of SNP involved in renal transport of uric acid, a mechanism that is significantly altered in patients with gout but is probably only minimally involved in cardiovascular, renal and metabolic diseases. The same procedure of spontaneous randomisation applied to genetic polymorphisms involving xanthine-oxidase have given completely different results leading to a possibility that serum uric levels per se are only partially representative of the negative effects of uric acid in some important populations of patients.

Fourth, the many adjustments that have been applied to the observational data should be re-considerd after the demonstration that elevated levels of uric acid can precede some of the adjusting factors (e.g hypertension) leading to an unfair conclusion in therms of causative role.

Finally, the threshold level for the different conditions related to uric acid seems to be largely different ranging from 4-5 mg/dl for cardio-metabolic diseases to 6-5 for gout. Most of the cross-sectional data have been analysed by considering as a threshold for elevated serum uric acid levels those qualifying for the diagnosis of gout (usually > 7 mg/dl) so attributing to the normal range a remarkable proportion of patients with an increased risk of cardio-metabolic disease with a consequent reduction in the discriminatory power of the analysis.

For all these reasons we do not believe the the puzzling interpretation of the role of serum uric acid beyond gout can be inspired by any huge analysis and review of all the available literature; more attention should be paid to the possibility of going beyond the plasma phenotype. Any comprehensive paper that does not consider the heterogeneity of the phenotype will have only the effect of increasing the uncertainty and reducing the probability to find a solution (if any) to a very interesting and unresolved problem.

Competing interests: No competing interests

15 September 2017
Claudio Borghi
Professor of Medicine
A.F.G Cicero
University of Bologna
Bologna, Italy
Re: Do patients at risk of infective endocarditis need antibiotics before dental procedures? Thomas J Cahill, Mark Dayer, Bernard Prendergast, Martin Thornhill. 358:doi 10.1136/bmj.j3942

We read with great interest the review article by Cahill et al (1) on the need for antibiotic prophylaxis prior to dental procedures in patients at risk of oral streptococcal endocarditis. The previous recommendation from NICE to abandon antibiotic prophylaxis (2) has been met with alarm in the cardiac surgical community (3). Cahill et al point out the increase in incidence of endocarditis in the UK since the introduction of the NICE guidelines but also highlight the lack of confirmatory evidence that the increase was due to the occurrence of more streptococcal endocarditis cases. It is lamentable that the official records do not permit subanalysis of the infecting organism, a situation which should be addressed urgently.

One of us (KB) has personally had three patients over a period of 10 years (since the NICE guidelines came into effect) who had conventional risk factors for endocarditis, who were not given antibiotic prophylaxis for invasive dental surgery and who subsequently developed dental streptococcal endocarditis.

It is right that Cahill et al acknowledged the great loss experienced by two families whose relatives died as a direct result of infective endocarditis following dental procedures. They do not mention whether these patients were known to be at high risk for endocarditis or not and we request that, where possible, they clarify this matter. Clearly nothing can be done to prevent dental-acquired endocarditis in patients without risk factors for it.

We commend the BMJ for publishing this article which considers a move back to permitting antibiotic prophylaxis for patients with prosthetic heart valves. This is something that cardiac surgeons have always considered to be mandatory.

1. Cahill T J, Dayer M, Prendergast B, Thornhill M. Do Patients at risk of infective endocarditis need antibiotics before dental procedures? BMJ 2017; 358: 368-371
2. National Institute for Health and Care Excellence (NICE), 2015. Prophylaxis against infective endocarditis. London: NICE (Available at:
3. Dayer M J, Chambers J B, Prendergast B, Sandoe J A, Thornhill M H. NICE guidance on antibiotic prophylaxis to prevent infective endocarditis: a survey of clinicians attitudes. QJM 2013; 106: 237-243.

Competing interests: No competing interests

15 September 2017
Keith G Buchan
Consultant Cardiothoracic Surgeon
Jonathan R Strickland, Shekinah G Chandy, Steven Hor Yong Keen
Aberdeen Royal Infirmary
Re: UK doctors re-examine case for mandatory vaccination Tom Moberly. 358:doi 10.1136/bmj.j3414

Fourteen responses so far. Not even one from those who favour mandatory vaccination.

A debate means arguments from both sides.

Evidence so far is conclusive. "There shall be no debate. Let the opponents talk or write. "

The wise men and women in Downing Street shall pronounce when they feel the time is right.

"It is a national emergency. Obey"

Competing interests: No competing interests

15 September 2017
JK Anand
Retired doctor
Free spirit