Search all rapid responses

All rapid responses

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: Prehabilitation: preparing patients for surgery Venetia Wynter-Blyth, Krishna Moorthy. 358:doi 10.1136/bmj.j3702

It is encouraging to read the realistic and balanced view of the role of prehabilitation in preparing patients for major surgery presented by Winter-Blyth and Moorthy (BMJ 2017;358:j3702). The case for preoperative optimisation of the patient as a route to improved postoperative outcomes is, as described, now gaining more widespread acceptance. We agree that the prescription of exercise within the healthcare setting is complex, ultimately requiring buy-in from the myriad of professionals involved in a patient’s journey to surgery: the GP, specialist nurse, surgeon, anaesthetist and oncologist to name but a few. This alone represents a significant but achievable challenge requiring education and clear communication within the multidisciplinary team1.

Change in attitude and indeed change in policy is required on a nationwide level2,3. Within the current politically-driven time to treatment framework, there is limited opportunity for vital risk-reduction strategies such as prehabilitation. Public perception focuses on undergoing surgery as soon as possible with limited understanding of the effect this can have on outcome4. This is particularly pertinent in cancer surgery, where an arbitrary 31 days is allocated from time of diagnosis to date of surgery. High risk patients comprise approximately 12% of the population undergoing major surgical procedures, but account for 80% of all mortality5. Adequately preparing such patients for the marathon of surgery within this time frame is optimistic at best.

As prehabilitation makes the deserved transition from research modality to key clinical process, we must continue to gather evidence for its benefit and use this to lobby those in power to acknowledge that time to treatment is a poor indicator of the quality of our surgical services. The impact of postoperative complications on quality of life is well documented6,7, with a subsequent domino effect of decreased long-term survival8. Concentrating investment in preoperative strategies to improve patients’ ability to cope with the stress of surgery rather than publicising artificial performance indicators represents far better use of tax-payers money, and a much safer method of marathon-proofing our patients.

1. Anderson AS, Caswell S, Wells M, Steele RJ. Obesity and lifestyle advice in colorectal cancer survivors - how well are clinicians prepared? Colorectal Dis. 2013 Aug;15(8):949-57.
2. Carli F, Gillis C, Scheede-Bergdahl C. Promoting a culture of prehabilitation for the surgical cancer patient. Acta Oncol. 2017 Feb;56(2):128-133.
3. Grocott MPW, Plumb JOM, Edwards M, Fecher-Jones I, Levett DZH. Re-designing the pathway to surgery: better care and added value. Perioper Med (Lond). 2017 Jun 20;6:9.
4. Alexander D, Allardice GM, Moug SJ, Morrison DS. A retrospective cohort study of the influence of lifestyle factors on the survival of patients undergoing surgery for colorectal cancer. Colorectal Dis. 2017 Jun;19(6):544-550.
5. Pearse RM, Harrison DA, James P et al. Identification and characterisation of the high-risk surgical population in the United Kingdom. Crit Care 2006, 10(3):R81.
6. Brown SR, Mathew R, Keding A et al. The impact of postoperative complications on long-term quality of life after curative colorectal cancer surgery. Ann Surg. 2014;259(5):916-923.
7. Derogar M, Orsini N, Sadr-Azodi O, Lagergren P. Influence of major postoperative complications on health-related quality of life among long-term survivors of esophageal cancer surgery. J Clin Oncol. 2012 May 10;30(14):1615-9.
8. Straatman J, Cuesta MA, de Lange-de Klerk ES, van der Peet DL. Long-Term Survival After Complications Following Major Abdominal Surgery. J Gastrointest Surg. 2016 May;20(5):1034-41.

Competing interests: No competing interests

21 September 2017
Katrina Anne Knight
Surgical Research Fellow in Perioperative Care
Professor Nanette Mutrie, Director of Physical Activity for Health Centre, University of Edinburgh, Professor Annie Anderson, Professor of Public Health Nutrition, University of Dundee, Professor Robert J C Steele, Division of Cancer Research, University of Dundee, Miss Susan J Moug, Consultant Colorectal Surgeon, Honorary Clincal Associate Professor, University of Glasgow.
Department of Surgery, Royal Alexandra Hospital and Academic Unit of Surgery, Glasgow Royal Infirmary
Royal Alexandra Hospital, Corsebar Road, Paisley, PA2 9PN
Re: Put more trust in the trustworthy and less in the untrustworthy to improve judgement of medicines Mary Madden. 358:doi 10.1136/bmj.j4202

As a bear of small brain, may I say that long words and long phrases of experts can be hard to understand in all their nuances.

Therefore, some of us seek answers from the experts, to very simple, brief questions.

Please look at my Rapid Response to Prof Cave.

Prof Cave called for a debate. I raised a few queries.

No answers yet from the experts in public health, in immunology, in pharmacology, in general practice.

Perhaps I am just one in a tiny minority who seek information, before reposing TRUST.

Competing interests: No competing interests

21 September 2017
JK Anand
Retired doctor
Free spirit
Peterborough
Re: State educated children do better at medical school Adrian O’Dowd. 358:doi 10.1136/bmj.j4239

Having graduated from a state school myself I find this article interesting but also somewhat unsurprising. State schools vary on a huge scale. Some have teachers who are genuinely interested in making a difference to the life and future of their students. A number of others are completely dissociated and just want to get by each day working with children that they feel are incapable of achieving any university or even college level career. The one thing that is true for all state schools I would have to say, is that interest and motivation has to come from within self. Finding someone to help you and show genuine interest in your thoughts involves you having that initial passion yourself and actively searching for assistance and opportunities.

Interestingly enough, I have also been to private schools at a younger age. The general difference is the expectation of you from your peers and teachers, hence spoon feeding is the general method of teaching. You are meant to achieve. You are believed in. This does teach you a lot subject matter wise however does it really ignite interest and self motivation? Why would you ever need that if someone is teaching you everything you need to know to do well in the future?

Don't get me wrong though- numerous students coming from private schools have genuine passion and interest for medicine. However it is possible that they did not have to fight as many obstacles to achieve their place. That in itself is a feat. A majority of state schools have students with a poorer self esteem and having the confidence that you can do a course like medicine can be rarer than in private schools. Nevertheless the students who manage to push through this- regardless of whether their parents or teachers helped them- have that initial task of developing an interest in medicine themselves. This I feel is the key difference between the two.

University is always different to high school. No-one will spoon feed you. You will be advised of where help is available and the staff are enthusiastic to do so, but you must identify this need and utilise the tools available. State school students presumably have done this for years anyway and will continue in their efforts to find opportunities even in medicine. Perhaps identifying the need for assistance is the struggle that privately educated students struggle with once in medical school? Perhaps if this was addressed the rates would be somewhat more even.

Competing interests: No competing interests

20 September 2017
Amritha Sastry
Medical Student
University of Aberdeen
Aberdeen
Re: Debating the future of mandatory vaccination Emma Cave. 358:doi 10.1136/bmj.j4100

Thanks to Dr Thomas for his shrewd and measured comments. I wonder whether the British government considered going down the path of the US Vaccine Injury Act in the 1980s and rejected it? This at least in theory took the legal decision to vaccinate out of the hands of the parents and placed it with the state. And while we have a very tardy and modest vaccine damage payment scheme in this country it remains the parent who is responsible for the decision - though the issue of whether consent is properly informed in many cases has been raised. It is an interesting question, apart from anything else, whether the state needs to take on this serious liability at such an awkward juncture in our history.

I suspect another difficulty is whether going down the route of other countries with financial sanctions and denial of services against refusers - leaving the wealthy and powerful to make their choice while being coercive for lesser citizens - would be acceptable in the United Kingdom. It sounds to me like humbug.

Competing interests: No competing interests

20 September 2017
John Stone
UK Editor
AgeofAutism.com
London N22
Re: Major report backs overhaul of US dietary guideline process Jacqui Wise. 358:doi 10.1136/bmj.j4340

Diets are a riot. There are many popular diets, but none of them seem to work. They all leave us hungry and weak, not satisfied or strong. What is a healthy diet?

A healthy diet is nutritious food without toxins or addictions. Despite their popularity, trusted toxins and addictions in our diet are common, covert causes of conflict and sickness. So we should avoid toxins like pesticides, herbicides, and fungicides; and we should avoid addictions like sugar, honey, chocolate, vanilla, cola, coffee, tea, alcohol, tobacco, and drugs. What should we eat?

We should eat organic food and follow a lacto-ovo-vegetarian diet. Organic food (which excludes chemicals) minimizes toxins, and a lacto-ovo-vegetarian diet (which excludes meat, chicken, and fish) minimizes our cravings for addictions. The result is an organic, addiction-free Lacto-Ovo-VEgetarian diet, which I call the “LOVE Diet," my acronymic recipe for health, which combines tasty vegetarian cuisine with whole dairy and eggs.

Contrary to popular opinion, we don't need meat, chicken, or fish. They lack balanced nutrition and cause addiction. The LOVE Diet replaces meat, chicken, and fish with beans, nuts, seeds, and whole grains, which offer more nutrition and less hunger or addiction. Delicious and nutritious, with satiety and sanity, the LOVE Diet is a recipe for peace and health, our most crucial but elusive goals.

The opposite of the LOVE Diet (nutrition) is the “HATE Diet” (addiction). The HATE Diet (Honey, Alcohol, Tobacco, Espresso) is a non-organic diet that includes meat, chicken, fish, and addictions. Addicting and afflicting, with cravings and ravings, the HATE Diet is a recipe for conflict and sickness, our everyday reality. So delete meat, and pledge veggies. Choose LOVE, not HATE.

Competing interests: No competing interests

20 September 2017
Hugh Mann
Physician
Retired
Re: Put more trust in the trustworthy and less in the untrustworthy to improve judgement of medicines Mary Madden. 358:doi 10.1136/bmj.j4202

The editing of the last paragraph of my letter has changed the sense of what I wrote.

Original
It is unhelpful that discussions on the placement and refusal of trust in health research continue to be infused with a pervasive 'deficit model' which implies that all public and professional scepticism of science is unfounded and that there is a need for corrective communication by experts, rather than a need to encourage broader debate that attends to those concerns

Published
Pervasive discussion of the “deficit model,” which implies that all public and professional scepticism of science is unfounded and that corrective communication by experts is necessary, is unhelpful. We need to encourage broader debate that attends to those concerns

The latter implies a criticism of the discussion rather than of the deficit model which pervades it. Discussion of the model is not pervasive, its use is. I think such a discussion would be useful. A corrected version incorporating your edits would read:

Pervasive use of a “deficit model,” which implies that all public and professional scepticism of science is unfounded and that corrective communication by experts is necessary, is unhelpful. We need to encourage broader debate that attends to those concerns

Competing interests: No competing interests

20 September 2017
Mary Madden
Lecturer in Applied Health Research
University of Leeds
Leeds
Re: A smoke-free generation? John Britton. 358:doi 10.1136/bmj.j3944

I have already pointed out the uselessness of the government’s July 2017 ‘A Tobacco Control Plan for England’ proposals [1].

Dr Britton may well lament that ‘There are many reasons why countries, rich or poor, fail to take adequate measures to prevent smoking.’ But no country – except Bhutan where the sale and distribution of cigarettes are prohibited – effectively prevents smoking.

There is only one measure that will produce a smoke-free society, but it is hardly ever mentioned, let alone seriously considered: banning the sale of all tobacco products.

symonds@tokyobritishclinic.com

1. http://nicotinemonkey.com/?p=1767

Competing interests: No competing interests

20 September 2017
Gabriel Symonds
General practitioner
Tokyo
Re: Pharmaceutical companies’ policies on access to trial data, results, and methods: audit study Igho Onakpoya, Ian Bushfield, Liam Smeeth, et al. 358:doi 10.1136/bmj.j3334

We read with interest the recent article by Goldacre and colleagues auditing clinical trial data sharing 1. One point we have noticed, however, is that whilst there are a number of articles calling for the sharing of clinical trial data 1 2, the access to and sharing of real-world/observational data receives little and arguably insufficient attention. This is despite the important uses of these data, as exemplified by the recent ‘weekend effect’ issue in the UK 3 4, as well as their application to National clinical guidelines 5.

The BMJ does not enforce a commitment to data sharing for observational studies 6, but all research articles are required to contain a data sharing statement 7. A review of the data sharing statements of 237 observational studies published in the BMJ between January 2015 and August 2017 revealed that 63% of studies had a statement implying that the data underlying the study could not be shared 8. Whilst there are likely many reasons for this, including patient confidentiality concerns, the result is generally reflective of the current state of observational research where many data sources across the world are not readily accessible, and nor is the data shared after a study is completed 9 10.

As noted by Davey-Smith in the BMJ over 20 years ago 11, shared data can be used to answer new questions about disease as well as validating the initial analyses. The former has been evidenced recently with trial data sharing 12 13 14. Policy and privacy issues to increase real-world data access and sharing need to be addressed as this is a potential barrier to scientific advancement. Improved, responsible data access and sharing could in turn allow for more effective use of limited healthcare resources and offers significant potential for improvements in healthcare.

References
1. Goldacre, B. et al. Pharmaceutical companies’ policies on access to trial data, results, and methods: audit study. BMJ 358, j3334 (2017).
2. Krumholz, H. M. & Peterson, E. D. Open Access to Clinical Trials Data. JAMA 312, 1002–1003 (2014).
3. Replies to A national health care data network is overdue. Available at: http://www.cmaj.ca/content/189/29/E951/reply#cmaj_el_733383. (Accessed: 2nd September 2017)
4. McKee, M. The weekend effect: now you see it, now you don’t. BMJ 353, i2750 (2016).
5. Oyinlola, J. O., Campbell, J. & Kousoulis, A. A. Is real world evidence influencing practice? A systematic review of CPRD research in NICE guidances. BMC Health Serv. Res. 16, 299 (2016).
6. Research | The BMJ. Available at: http://www.bmj.com/about-bmj/resources-authors/article-types/research. (Accessed: 2nd September 2017)
7. Groves, T. Managing UK research data for future use. BMJ 338, b1252 (2009).
8. McDonald, L. et al. A review of data sharing statements in observational studies published in the BMJ: A cross-sectional study. F1000Research 6, 1708 (2017).
9. García Álvarez, L. et al. Data linkage between existing healthcare databases to support hospital epidemiology. J. Hosp. Infect. 79, 231–235 (2011).
10. Moulis, G. et al. French health insurance databases: What interest for medical research? Rev. Médecine Interne 36, 411–417 (2015).
11. Smith, G. D. Increasing the accessibility of data. BMJ 308, 1519–1520 (1994).
12. Burns, N. S. & Miller, P. W. Learning What We Didn’t Know — The SPRINT Data Analysis Challenge. N. Engl. J. Med. 376, 2205–2207 (2017).
13. Guinney, J. et al. Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data. Lancet Oncol. 18, 132–142 (2017).
14. Wilkerson, J. et al. Estimation of tumour regression and growth rates during treatment in patients with advanced prostate cancer: a retrospective analysis. Lancet Oncol. 18, 143–154 (2017).

Competing interests: SR and LM are employees of Bristol-Myers Squibb. AS, AS, SG and RW are employees of Evidera.

20 September 2017
Sreeram Ramagopalan
Epidemiologist
Laura McDonald, Anna Schultze, Alex Simpson, Sophie Graham, Radek Wasiak
Bristol-Myers Squibb
Uxbridge
Re: Misdirected care in a misdirected world Kamran Abbasi. 358:doi 10.1136/bmj.j4256

BY WRITING THIS I DON'T WANT TO HURT ANYONE FEELINGS AND IT IS REFERENCE BASED .

Well said "Misdirected care in a Misdirected world".

the present era is Kali Yuga; Lord Krishna's departure marks the start of Kali Yuga and is associated with the demon Kali (not to goddess Kālī). There are four Yugas: they are called Satya Yuga, Treta Yuga, Dwapara Yuga and Kali Yuga. Human civilization degenerates spiritually during Kali Yuga, which is referred to as the Dark Age. People will be addicted to intoxicating drinks & drugs, and sin will increase (1,2).
According to Aryabhatta the mathematician and astronomer, Kali Yuga started in 3102 BCE (3).

The Crisis of the Modern World: A misdirected population leads to a "misdirected world". The best way to handle it is to "Educate the people" and change the "Attitude towards the right path" by promoting and accepting the value of Yoga, meditation and prayers (4).

Believe in nature & the green revolution, avoid global warming, maintain daily routine, which helps in curbing lifestyle related diseases.

Regards,

References:

1. The Bhagavata Purana (1.18.6), Vishnu Purana (5.38.8), and Brahma Purana (212.8), the day Krishna left the earth was the day that the Dvapara Yuga ended and the Kali Yuga began.

2. S.V Gupta. Units of Measurement: Past, Present and Future. International System of Units. Springer. p. 3

3. H.D. Dharm Chakravarty Swami Prakashanand Saraswati. Encyclopedia Of Authentic Hinduism The True History and the Religion of India, Hardbound, 2nd Edition, 2003 ,ISBN 0967382319

4. Lings, Martin. The Eleventh Hour: The Spiritual Crisis of the Modern World in the Light of Tradition and Prophecy. Cambridge, UK: Archetype, 2002

Competing interests: No competing interests

20 September 2017
Dr.Rajiv Kumar
Faculty
Dept. of Pharmacology, Government Medical College & Hospital
Chandigarh 160030. India.
Re: Non-specific effects of measles, mumps, and rubella (MMR) vaccination in high income setting: population based cohort study in the Netherlands Fiona R M van der Klis, Elisabeth A M Sanders, Marianne A B van der Sande, Mirjam J Knol, et al. 358:doi 10.1136/bmj.j3862

Beneficial non-specific reduction in hospital admissions for respiratory infections following MMR and MenC vaccinations in the Netherlands

We appreciate that Tielemans et al.(1), using Dutch population data on vaccinations and hospital admission for infectious diseases, tested our findings of non-specific effects (NSEs) of the live attenuated measles-mumps-rubella (MMR) vaccine in Denmark(2). We found the transition from the third DTaP-IPV-Hib (DTP3) to MMR to be associated with a hazards ratio (HR) of 0.86 (95%CI=0.84-0.88). The Dutch study finds much stronger beneficial effect estimates for the transition from the fourth DTaP-IPV-Hib-PCV (DTP4) to MMR+MenC (HR for all admissions of 0.40 (0.38-0.41); for >1 day admissions 0.62 (0.57-0.67)), but also strong beneficial effect estimates for the previous transition from DTP3-to-DTP4 (HR all admissions 0.48 (0.46-0.51); >1 day 0.69 (0.63-0.76)). The authors conclude that healthy vaccinee bias at least partly explains the lower rates of admission after MMR and add that though NSEs cannot be excluded, NSEs cannot be distinguished from bias. The authors therefore emphasise the importance of caution in the interpretation of observational studies on the NSEs of vaccines.

There are several important contextual differences between the Danish and the Dutch studies. For instance, Denmark provides MMR at 15 months, whereas the Netherlands provides MMR+MenC vaccines at 14 months, and the NSEs of a live vaccine vs. co-administration of a live vaccine and a non-live vaccine have been shown to differ(3).

Most important in relation to healthy vaccinee bias is the difference in the organisation of vaccination. In the Netherlands, all children have pre-scheduled vaccination appointments, so 99.6% of all children had received MMR+MenC vaccine by 24 months of age. Judged by Figure 2(1), it was the sick children, who were delayed, since the admission rate increased in the unvaccinated children after 14 months. If almost all are vaccinated except sick children, this creates a strong healthy vaccinee bias, or maybe rather “unhealthy non-vaccinee bias”. In Denmark, parents have to schedule the vaccination appointments themselves; less than 90% had received MMR by 24 months; therefore the group of delayed children is more diverse and the admission rate did not increase in the unvaccinated children after 15 months(2).

It could be discussed whether it is meaningful to compare vaccinated versus unvaccinated children in settings like the Dutch, with severe healthy vaccinee bias. Tielemans et al. propose one way to control for healthy vaccinee bias: if we assume that the HR associated with the transition from DTP3–to-DTP4 is due to healthy vaccinee bias, then the relative difference in the HRs for DTP3-to-DTP4 and DTP4-to-MMR+MenC could be ascribed to the NSEs of MMR+MenC(1). The authors do not present the calculation, but if we use the HR for all admissions for the transition from DTP3-to-DTP4 as an indication of the “baseline” healthy vaccinee bias, then an adjusted HR for all admissions for the transition from DTP4-to-MMR+MenC can be estimated as 0.40/0.48=0.83 (95% CI=0.78-0.89). The correction of a HR for a vaccine by adjustment for the HR of another vaccine represents one way to deal with healthy vaccinee bias. It cannot be excluded that healthy vaccinee bias could be different in different age groups and the true estimate of the NSEs of MMR+MenC might well be larger or smaller than 17% (11-22%).

Are there other ways to control for healthy vaccinee biases? We have previously used triangulation methods to examine whether NSEs are the most logical explanation for all the data available. In the Danish study, we showed that DTP administered after MMR was associated with increased risk of admission, a tendency which cannot be explained by healthy vaccinee bias. Furthermore, both observational studies and RCTs(4) from low-income countries have suggested that measles vaccine is associated particularly with lower risk of respiratory infections. We therefore tested whether the reduction in admissions differed by disease category, or was similar for all categories as would be expected if healthy vaccinee bias were the main explanation. Corroborating the findings from low-income countries, the effect of MMR was smallest for gastrointestinal infection admissions (HR=0.93 (0.87-1.00)), being stronger for lower respiratory infections (HR=0.80 (0.76-0.84); p=0.001 for same effect as for gastrointestinal infections) and for upper respiratory infections (HR=0.86 (0.82-0.89); p=0.058).

In the Dutch study, MMR+MenC was likewise associated with the smallest reduction in gastrointestinal infection admissions (0.69 (0.61-0.78)) whereas the reductions were significantly stronger for lower respiratory infections (HR=0.57 (0.49-0.65); p<0.046) and for upper respiratory infections (HR=0.36 (0.34-0.37); p<0.001). In contrast, DTP4 was associated with the same reductions in gastrointestinal (HR=0.70 (0.61-0.79)), lower respiratory (HR=0.79 (0.67-0.82)) and upper respiratory infection admissions (HR=0.72 (0.62-0.82)) (p=0.299 for same effect; estimates for >1 day admissions, as no estimates for all admissions were reported)). Thus, relative to the reduction for gastrointestinal infections, MMR+MenC was associated with stronger reductions in admissions for lower respiratory infections (HR=0.80 (0.65-0.98)) and upper respiratory infections (HR=0.77 (0.64-0.93)), and the effect on lower respiratory infections and upper respiratory infections differed significantly between MMR+MenC vaccination and DTP4 vaccination.

Thus, there are two observations from this triangulation analysis, which cannot be explained by healthy vaccinee bias: First, the pattern of stronger reductions for respiratory infections than for gastrointestinal infections after MMR(+/-MenC) vaccinations seen in both the Netherlands and Denmark. Second, the effect of MMR(+MenC) and DTP3/4 on respiratory infections differed significantly in both the Netherlands and Denmark, with beneficial effect estimates of MMR(+MenC) but the opposite tendency for DTP4. Thus, in spite of severe healthy vaccinee bias, there was still important information supporting beneficial NSEs of MMR+MenC on respiratory infections in the Dutch study. Reassuringly, a beneficial effect of MMR on respiratory infections has also recently been reported by studies from USA(5) and Italy(6).

There is increasing epidemiological and immunological evidence that NSEs of vaccines are important(2-7). The number of RCTs testing NSEs is going to be limited for ethical and financial reasons. Hence, we rely largely on observational studies to assess NSEs. As shown here, using triangulation methods it is possible to distinguish NSEs from bias, even in settings with severe healthy vaccinee bias. Hence, we hope the Dutch call for caution is not interpreted as a call for caution against observational studies of the NSEs of vaccines.

Christine S Benn, Signe Sørup, Peter Aaby

Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S; OPEN, Department of Clinical Research, and Danish Institute for Advanced Study, University of Southern Denmark/Odense University Hospital, Denmark

References
1. Tielemans SMAJ, de Melker HE, Hahné SJM, Boef AGC, van der Klis FRM, Sanders EAM, van der Sande MAB, Knol MJ. Non-specific effects of measles, mumps, and rubella (MMR) vaccination in high income setting: population based cohort study in the Netherlands. BMJ 2017;358:j3862
2. Sørup S, Benn CS, Poulsen A, Krause TG, Aaby P, Ravn H. Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections. JAMA 2014;311:826-35
3. Higgins JPT, Soares-Weiser K, López-López JA, Kakourou A, Chaplin K, Christensen H, Martin NK, Sterne JAC, Reingold AL. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 2016;355:i5170
4. Martins CL, Benn CS, Andersen A, Balé C, Schaltz-Buchholzer F, Do VA, Rodrigues A, Aaby P, Ravn H, Whittle H, Garly ML. A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions. J Inf Dis 2014;209;1731-8
5. Bardenheier BH, McNeil MM, Wodi AP, McNicholl J, DeStefano F. Risk of nontargeted infectious disease hospitalizations among U.S. children following inactivated and live vaccines, 2005-2014. Clin Inf Dis 2017;epub
6. La Torre G, Saulle R, Unim B, Meggiolaro A, Barbato A, Mannocci A, Spadea A. The effectiveness of measles-mumps-rubella (MMR) vaccination in the prevention of pediatric hospitalizations for targeted and untargeted infections: a retrospective cohort study. Human Vaccines & Immunotherapeutics 2017; 13: 1879-83
7. Benn CS, Netea MG, Selin LK, Aaby P. A small jab - a big effect: nonspecific immunomodulation by vaccines. Trends Immunol. 2013 Sep;34(9):431-9.

Competing interests: No competing interests

20 September 2017
Christine S Benn
Center Leader, Professor
Signe Sorup, Peter Aaby
Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S; OPEN, Department of Clinical Research, and Danish Institute for Advanced Study, University of Southern Denmark/Odense University Hospital, Denmark

Pages