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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: Keeping older doctors in the job David Oliver. 355:doi 10.1136/bmj.i6260

Dear Doctor David Oliver,
Recent evidence clearly demonstrates that patients treated by older physicians had higher mortality rates than patients cared for by younger physicians. [1]
So the logical answer to your question is "No, we should not frenetically keep older doctors in the job to counteract NHS shortages."

Competing interests: No competing interests

17 May 2017
Stavros Saripanidis
Consultant in Obstetrics and Gynaecology
Kalamaria, Thessaloniki, Greece
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Re: Measles outbreak in Somali American community follows anti-vaccine talks Owen Dyer. 357:doi 10.1136/bmj.j2378

Author at one place writes:

.....The advice came as Minnesota’s public health department was urging unvaccinated people to take the MMR as soon as possible because, even after infection, it can prevent measles developing if taken within 72 hours.....

Here, let us explain, why.

The incubation period of natural measles (which is spread by respiratory route, viz. droplet infection) is 10-12 days till onset of fever and 14 days till onset of rash. If this route is circumvented by artificially inducing measles, as by injecting a live attenuated vaccine, this incubation period can be shortened to 7 days (i.e. 72 hours or 3 days less). So, if the vaccine is given very early in the incubation period, immunity begins to be induced by the vaccine before natural infection gets established.

Competing interests: No competing interests

17 May 2017
Neeru Gupta
Scientist F
Jugal Kishore , Akshun Jani Neeta Kumar
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029.
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Re: Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data Arja Helin-Salmivaara, Edeltraut Garbe, James M Brophy, et al. 357:doi 10.1136/bmj.j1909

This result should not be at all surprising. Low dose aspirin has a beneficial effect on inhibiting COX-1 which produces prostaglandins, most of which are pro-inflammatory, and thromboxanes, which promote clotting. However in higher doses aspirin loses its anti-clotting activity effect by inhibiting COX-2 in endothelial cells resulting in lower levels of the anti-coagulant, prostacyclin thus increasing the risk of thrombus and associated heart attacks and other circulatory problems. This is why aspirin is given at the low dose of 75mg (or 100mg) as an antiplatelet agent. Aspirin at therapeutic analgesic doses like any other NSAID will have an effect on inhibiting prostacyclin that outweighs any beneficial effect on reducing COX-1. I wonder how many patients continue on 75mg of aspirin while taking therapeutic doses of an NSAID which totally negates its effect?

Competing interests: No competing interests

17 May 2017
David Bareford
Retired consultant haematologist
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Re: Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data Arja Helin-Salmivaara, Edeltraut Garbe, James M Brophy, et al. 357:doi 10.1136/bmj.j1909

While Bailey et al.’s total cohort size (446,763) was relatively large and derived from four observational sources from Canada, Finland, and the UK, they represented only half of the potentially eligible studies identified through their literature search. Data from four studies could not be included for “ethicolegal restrictions placed by health authorities on transfer of (individual patient data) to third parties”. Per Web Appendix 1, if this data were available it would have included 98,370 patients (experiencing 4,850 MI events) from the US Medicare system (1), 716,935 patients (8,852 MI events) from the UK NHS (2), 107,092 patients (8,970 MI events) from the Danish health system (3), and 48,566 patients (3,600 MI events) from a mixed group representing the US, Canada, and the UK. (4)

The authors did not specify the particular nuance of the refusals but these might have included a lack of explicit patient consent to share data, commercial interests, or a lack of resources available to support data transfer agreements. In total, this represents nearly a million patients whose experiences have not contributed to a wider learning health system, including 26,272 people who experienced an MI event. When tragic circumstances assault our daily lives, we try to take some solace from the notion that what has happened to us might inform or warn or protect those that come after us. In a nationally representative sample of US citizens conducted by the Institute of Medicine, 91% of respondents agreed that their health data should be used to improve the care of future patients with the same condition (5).

By contrast, some data-driven consultancies boast that by accessing the personal details of many millions of citizens, harvested through commercial vendors, government agencies, and social media, they were able to effectively “micro-target” political messaging in the 2016 US Presidential election and the Brexit referendum (6). Given the global reach of personal data gathered online it seems plausible that personal data on many of the million patients excluded from Bailey et al.’s study by thoughtful and principled health researchers might be sitting on the hard drives of data scientists supporting political ideologies that seek to remove protections against medical bankruptcy, discrimination, or worse.

While it is important we learn the lessons of Care.Data, it appears a remarkable situation when seekers of truth have one arm tied behind their back while the unscrupulous are given a free rein.


(1) Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S. Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: High-risk subgroups and time course of risk. Arthritis Rheum 2006;54:1378-89.

(2) Garcia Rodriguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol 2008;52:1628-36.

(3) Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med 2009;169:141-9.

(4) Ray WA, Varas-Lorenzo C, Chung CP, et al. Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes 2009;2:155-63.

(5) Grajales F, Clifford D, Loupos P, Okun S, Quattrone S, Simon M, Wicks P, Henderson D. Social networking sites and the continuously learning health system: a survey. Washington (DC): Institute of Medicine of the National Academies. 2014 Jan 23.
(6) Grassegger H, Krogerus M. The data that turned the world upside down., Accessed May 15th, 2017

Competing interests: Full competing interests on

17 May 2017
Paul J Wicks
VP of Innovation
160 2nd Street
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Re: Pharmacists state ambition to expand their role in community health Geoff Watts. 342:doi 10.1136/bmj.d274

Geoff Watts reported in the BMJ that "failure to make full use of the knowledge of pharmacists has long been one of the profession’s recurrent preoccupations, regardless the awareness of the role that pharmacists could have—and in some cases already do—in the management of chronic health problems such as obesity, smoking, and asthma". A recent publication in BMC Health Services1 can offer a concrete example that community pharmacists do hold a pivotal role in asthma care beyond medicine dispensing and their contribution adds value to health service delivery in terms of improved clinical effectiveness, medicines adherence, quality of life, but also cost effectiveness for the NHS and the society overall.

Results from one of the largest trials in pharmacy practice in terms of numbers of pharmacists and asthmatic patients, suggest that the Italian Medicines Use Review (I-MUR) service provided by community pharmacists to asthmatic patients is more effective and cost effective than usual care, supporting its implementation in national practice (see box).

Is the profession allowed to say that pharmacists have a role in community care beyond dispensing and we can make full use of their knowledge and skills? The authors say yes, and believe that pharmacy-based patient-centred and clinically-oriented services like I-MUR could confirm that the pharmacists are important players within the team of healthcare professionals and they score well in health service delivery.

1 Manfrin A, Tinelli M, Thomas T, Krska J. A cluster randomised control trial to evaluate the effectiveness and cost-effectiveness of the Italian Medicines Use Review (I-MUR) for asthma patients. BMC Health Services Research 2017. DOI: 10.1186/s12913-017-2245-9
Box: Key features of the Italian medicines use review (I-MUR)

1- The innovation: the Italian medicines use review (I-MUR) service.

I-MUR service consists of a structured and systematic interview conducted in a private area of the pharmacy that focuses on five different dimensions: asthma symptoms; medicines used; attitude towards medicines; the extent to which patients take medicines as prescribed by their doctor (adherence); and identification of pharmaceutical care issues (PCIs).

2- Its evaluation: the I-MUR trial.

The I-MR trial involved 283 pharmacists and 1263 patients from 15 different regions of Italy. The purpose of the study was to assess whether I-MUR service is:
- Effective - Is it able to improve asthma control (when asthma symptoms are well managed), optimise the number of medicines used, identify and resolve issues related to the use of medicines, and increase the adherence to medicines (compared with usual care provided by the community pharmacist)? Does its effectiveness vary over time? Increase, decrease or remain stable?
- Cost-effective - Is asthma control accompanied by an improvement of quality of life and a decrease in costs (for the health care system and society overall)? What is the probability of being cost- effective? Does the cost -effectiveness vary over time?

3- The I-MUR service is effective and its effectiveness increased over time.

- Patients who received the I-MUR service showed a probability of achieving asthma control almost double (1.8) compared to those who did not receive after only 3 months. In addition, the positive effect of the I-MUR service increased over time; the percentage of increase in controlled patients was overall 42% at 9 months.
- The I-MUR service enabled to optimise the number of medicines used by patients (reduced by 8%). The median number of medicines taken by the patients before I-MUR was 5, and decreased to 4 after 3 months; this value remained constant over time (at six month follow-up).
- In 65% of cases, during the I-MUR consultation the pharmacists were able to identify key issues related to medicines utilisation, including: lack of patient education, lack of monitoring, possible discrepancy between prescribed and real dose taken.
- The patient adherence to therapy increased by 35% after 3 months and increased further reaching 40% at 6 and 9 months after the intervention. The more the patients followed their asthma treatment the more their asthma was controlled. Furthermore, clear link was identified between adherence to treatment and asthma control.

4- The I-MUR service is cost effective and cost saving. Its success increased over time.

The cost effectiveness analysis showed that I-MUR service is more cost-effective compared to usual service and it is accompanied by saving costs for the NHS sector and the society overall (from 3 months onward) and increased quality of life (from 6 months onward). The probability of being cost-effective doubled from 50% at 3 months to 100% at 9 months.

5- Its implementation.

This study demonstrates that the I-MUR service, which is the first cognitive pharmaceutical service to be delivered in Italy, was both effective and cost-effective. The Italian Government and Ministry of Health have since promoted a change of community pharmacy practice, with the I-MUR being the first nationally funded cognitive pharmaceutical service in Italy. The work has supported a significant cultural shift in Italian community pharmacy practice, from a mainly logistic to a more patient-centred and clinically-oriented role of the community pharmacist in delivery of health care.

Competing interests: No competing interests

17 May 2017
Michela Tinelli
Assistant Professorial Research Fellow
Andrea Manfrin (University of Kent, School of Pharmacy)
Personal Social Services Research Unit, the London School of Economics
Houghton Street London WC2A 2AE
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Re: Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data Arja Helin-Salmivaara, Edeltraut Garbe, James M Brophy, et al. 357:doi 10.1136/bmj.j1909

I fully agree with Stephen Evans's response, of course. I would like to add that the clinical trial meta-analyses that serve as the foundation of the reality of the risk has shown risk only for use longer than 90 days and maximal approved dosing of NSAIDs. This represents about 5% of NSAIDs users, at most. For the vast majority of NSAIDs users, no risk has actually been demonstrated, and the present meta-analysis does not change this.

The major risk of the epi studies, as stated by Stephen Evans, is that a user of NSAIDs is not the same as a non user, even if it is the same patient. In addition to the possible protopathic bias (using the drug for early symptoms of coronary disease), there can be indication bias: acute pain itself increases heart rate and blood pressure (myocardial oxygen consumption), so that the indication for the use of NSAIDs may be a cause for MI. This is rarely discussed.

In last week's Bordeaux PharmacoEpi Festival, it was again stated that non-use is the wrong comparator in pharmacoepidemiology and should not be used. It is not the same as placebo. Drugs are always used for a reason, and users are not the same as non-users, and vice versa. Anyone with toothache or sore ("strep") throat can appreciate that. The comparator should be another drug with the same indication and a different mechanism of action, such as paracetamol, ideally, which has exactly the same indications and usage patterns as NSAIDs. Of course lower effectiveness of paracetamol on pain might leave residual confounding (persistence of pain). Eventually celecoxib might be a good comparator since apart from one clinical trial (APC) there is no indication of actual risk in any epidemiological study at this time. Can the study be rerun using celecoxib as reference, to confirm that other NSAIDs are really associated with increased risk of MI?

Incidentally, the decreasing risk with time is in contradiction with clinical trial data, and may be associated with depletion of susceptibles (but then why did it not appear in clinical trials), or with the indication for initiating NSAIDs.

My fear is that many patients or prescribers may be wary of what in the end is probably a very small risk, and shun NSAIDs for common pain in patients above the age of 50, prescribing opiates instead. What is the role of the "MI risk" of NSAIDs on the prescription opiate epidemic that resulted in several thousand yearly documented deaths in the US?


Nicholas Moore

Competing interests: I have been working on NSAIDs and especially low-dose NSAIDs for years, and am still not really convinced by the reality of the risk associated with short-term use of low-dose NSAIDs, or for that matter with any NSAID except high-dose, especially rofecoxib, for at leat 3 months, and preferably one year. Someof my earlier studies have been financed by Pharma companies (e.g., the PAIN study in the '90s), but none within the past 5 years.

17 May 2017
Nicholas Moore
professor of pharmacology
university of Bordeaux
146 rue Leo Saignat
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Re: Montgomery and informed consent: where are we now? Wojtek Wojcik, Jane E Norman, et al. 357:doi 10.1136/bmj.j2224

I find it strange that David A. Stephenson, Q.C., asks (12 May):

‘First, the decision in Montgomery purports to accord with the current (2008) GMC guidance on consent. If this is so, one might then wonder why change to the GMC’s guidance would be required in the light of Montgomery.’

Well, the Mental Capacity Act’s section 3 enshrined Informed Consent in English and Welsh law just before 2008: although the MCA does not use the term, it clearly did that [even if many people failed to notice].

Montgomery has more recently made it clear that Informed Consent is in fact the law for the whole of the UK (and has been since before the year 2000).

The GMC writes guidance which covers all of the UK.

Did I misunderstand why the question was posed [and I could not read the full article] ?

PS Although the above analysis is I think correct, I would point out that I consider the GMC's '2008 interpretation' of parts of the MCA - in particular how the Act applies to family carers - to be flawed, and therefore that it does need alteration.

Mike Stone @MikeStone_EoL

Competing interests: No competing interests

17 May 2017
Michael H Stone
Retired Non Clinical
None Private Individual
Coventry CV2 4HN
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Re: Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline Romina Brignardello-Petersen, Stijn Van de Velde, Rachelle Buchbinder, Martin Englund, et al. 357:doi 10.1136/bmj.j1982

Dr. Coates suggests that some patients with degenerative knee disease benefit from arthroscopic surgery and that expert surgeons can identify such patients. These calls for ‘judicious use’ and ‘personalised medicine’ are not new and while well intentioned are in this case, dangerously misguided. Arthroscopy has been used for degenerative knee disease for decades with clinicians always believing that they could identify the patients likely to derive a benefit from surgery.

The ability of expert surgeons to correctly identify such patients was first seriously questioned in 2002 in a randomised controlled trial (RCT) by Moseley and colleagues, which found that there was no benefit in patients with severe osteoarthritis (1). In response, many experts asserted that several other related groups of patients would benefit – younger patients, patients with pain but without imaging evidence of osteoarthritis, patients with meniscus tears, and patients with mechanical symptoms such as clicking and intermittent locking (2).

There are now 13 published RCTs, which include a substantial proportion of patients with characteristics in whom experts had claimed would benefit from surgery (3). As a whole, the RCTs provide high certainty evidence that arthroscopic surgery does not confer an important symptomatic benefit (4). Importantly, we recognize that most patients experience an improvement after arthroscopic surgery (5). but the effect is no different than conservative management, including sham surgery, suggesting that the benefit is not due to the surgery itself (6).

In the fifteen years since the negative RCT by Moseley in 2002 (1), millions of people have received unjustified surgery. The commonly used argument that this procedure “works in my hands” can no longer be accepted – the burden of proof is on those who posit this argument. If some clinicians believe that they can correctly identify patients who will benefit from surgery despite overwhelming evidence to the contrary, they should prove it with a high quality RCT. Until such time, no patient should be subjected to a procedure that probably has no important benefit.

1. Moseley JB, O'Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002;347:81-8.
2. Ewing W, Ewing JW. Arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002;347:1717-9; author reply 1717-9.
3. Brignardello-Petersen R, Guyatt GH, Buchbinder R, et al. Knee arthroscopy versus conservative management in patients with degenerative knee disease: a systematic review. BMJ Open 2017;7:e016114.
4. Devji T, Guyatt GH, Lytvyn L, et al. Application of minimal important differences in degenerative knee disease outcomes: a systematic review and case study to inform BMJ Rapid Recommendations. BMJ Open 2017;7:e015587.
5. Siemieniuk RA, Harris IA, Agoritsas T, et al. Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline. BMJ 2017;357:j1982.
6. Sihvonen R, Paavola M, Malmivaara A, et al. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med 2013;369:2515-24.

Competing interests: No competing interests

17 May 2017
Reed A.C. Siemieniuk
Reed A.C. Siemieniuk, Martin Englund, Rudolf W. Poolman, Anne Lydiatt, Helen Macdonald, Lyubov Lytvyn, Thomas Agoritsas, Lise Helsingen, Casey Quinlan, Annette Kristiansen, Ian A Harris
McMaster University
1280 Main St West
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Re: Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study Maki Inoue-Choi, Sanford M Dawsey, Christian C Abnet, et al. 357:doi 10.1136/bmj.j1957

Dear Editor,

We were interested to read Etemadi at al’s paper on mortality from different causes associated with meat, heme iron, nitrates, and nitrites1. It is our view that the hazards attributed to nitrate are due to other factors other than nitrate. The estimate of nitrate consumption is based on the processed meat consumption. Meat consumption is an inappropriate way to estimate nitrate exposure from the diet.

It is estimated that in the average Western diet 1-2 mmol/day of nitrate is consumed, the majority of this from vegetable sources2. Further, human beings synthesise around 1 mmol/day from the oxidation of endogenous nitric oxide synthesis3. In the present study, those in the highest category of meat-derived nitrate consumption were ingesting on average approximately 0.035mmol/day from meat sources. In this context it would seem unlikely that nitrate in itself would be associated with harm.

In contrast to the data presented here there is growing evidence that dietary nitrate may offer significant health benefits. There are observational data4 and randomised control trials5 demonstrating lower blood pressure with exposure to inorganic nitrate far in excess of the quantities described as associated with risk in Etemadi’s paper. This would be expected to be associated with lower risk of mortality from the multiple cardiovascular disease states examined in the study. Multiple other benefits have been demonstrated including in host defence, improvements in exercise efficiency and protection against ischaemia-perfusion injury 6.

It is also perhaps salient to note in a wide ranging review the World Health Organisation came to the conclusion ‘‘Overall, the epidemiological studies showed no consistently increased risk for cancer with increasing consumption of nitrate”.7

1. Etemadi A, Sinha R, Ward MH, Graubard BI, Inoue-Choi M, Dawsey SM, Abnet CC. Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ 2017; 357.

2. Bonnell A. Nitrate concentrations in vegetables. Epidemiological studies in humans. Proceedings of the International Workshop on Health aspects of nitrate and its metabolites (particularly nitrite). European Commission: Strasbourg, 1995.

3. Forte P, Kneale BJ, Milne E, Chowienczyk PJ, Johnston A, Benjamin N, Ritter JM. Evidence for a Difference in Nitric Oxide Biosynthesis Between Healthy Women and Men. Hypertension 1998; 32(4): 730-734.

4. Smallwood MJ, Ble A, Melzer D, Winyard PG, Benjamin N, Shore AC, Gilchrist M. Relationship Between Urinary Nitrate Excretion and Blood Pressure in the InChianti Cohort. Am J Hypertens 2017.

5. Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension 2015; 65(2): 320-327.

6. Gilchrist M, Winyard PG, Benjamin N. Dietary nitrate - Good or bad? Nitric Oxide 2010; 22(2): 104-109.

7. Speijers G, Brandt PAvd. Nitrate. Joint FAO/WHO Expert Committee on Food Additives: Geneva, 2003.

Competing interests: MG has previously received financial support from James White Drinks Ltd for the development of a nitrate-depleted form of beetroot juice.

16 May 2017
Mark Gilchrist
Renal Registrar
Amy Riddell, Angela C. Shore
University of Exeter
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Re: Clinical governance and the role of NHS boards: learning lessons from the case of Ian Paterson Kieran Walshe, Naomi Chambers. 357:doi 10.1136/bmj.j2138

The salient aspect in common of Mid-Staffs and Paterson is the prevailing of institutional interests over patients' safety. Of course some NHS managers, and some sociopaths, may be doctors.

The harms here are from decisions that were taken by senior management to persist in cutting staff posts, or to close down potentially damaging complaints in order to protect their institution.

In both cases, patients were put directly at risk as a result of these decisions.
In the case of MidStaffs, even more senior managers then decided to close down NICE's work on the Francis Inquiry's recommendations on safe clinical staffing ratios.

Such decisions are indicative of the culture of management, not a culture of Medicine. It's inaccurate and unhelpful to caption the article as a look at the venality of the "club" of Medicine, when it is clearly management decisions that require scrutiny.

These tensions in the NHS have never been more relevant, particularly as managers in untenable situations seem prone to ape the dissociative behaviour we see so much of from cognitively dissonant Politicians.

Competing interests: No competing interests

16 May 2017
Nick Mann
Well St Surgery E9 7TA
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