Tag Archives: Director’s Choice – From the Journals

Two Hundred and Two Ex-(American) Footballers’ Brains Analysed After Death – This You Must Read

Who would have thought that American football could be so damaging to the brain? Boxing yes. Here force is targeted at the container for the brain. However, it turns out that other contact sports may also damage the brain according to a recent study of 202 ex-footballers who donated their brains before death.[1] The clinical condition of the patients was recorded and correlated with histopathological finding. The mean age at death is rather young at 66. Hold on to your seat and read on to learn that fully 87% of football players’ brains fulfilled the histopathological criteria for chronic traumatic encephalopathy (a progressive neurodegenerative disorder associated with repetitive head trauma). In fact it was present in 110 of the subsample of 111 footballers who were lucky (unlucky) enough to make the National Football League (NFL). Further, 86% of these NFL players had severe pathology. Yes, brains may be more willingly donated when cognitive deterioration is present than when it is not, leading to inclusion bias. A prospective study is needed. But should we wait the 20-40 years needed for the results? Even if this study has overestimated the effect, the bias could not create so large an association if there were none. Would you encourage your grandchildren to play? If your heart packs up, your lungs fail or your pancreas turns cancerous, you die as yourself. But if your cerebral cortex is damaged you live as someone else.

— Richard Lilford, CLAHRC WM Director


  1. Mez J, Daneshvar DH, Kiernan PT, et al. Clinopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA. 2017; 318(4): 360-70.

Vaccination Savings

We know that vaccination is one of the most cost-effective interventions in terms of improving public health, but it can only be at its most effective if it is encouraged and supported by policy-makers and government officials. A recent paper in the Bulletin of the World Health Organization looked at the potential economic benefits of providing ten different vaccinations in 73 low- and middle-income countries.[1] These included vaccinations against hepatitis B, measles, rubella, and yellow fever. The authors found that if vaccinations were given routinely between 2001 and 2020, not only would 20 million children avoid death, but there would also be an estimated saving of $347 billion. This figure is predominantly made up of lifelong productivity gains from deaths avoided ($330 billion), but also from disabilities avoided ($9.4 billion), treatment costs ($4.5 billion), transport costs ($0.5 billion), and lost caregiver wages ($0.9 billion). Further they estimate that $820 billion would be saved from the broader economic and social value of vaccinations. The biggest contributor to these estimates was vaccination against measles, followed by H. influenza type b, S. pneumoniae, and hepatitis B.

— Peter Chilton, Research Fellow


  1. Ozawa S, Clark S, Portnoy A, et al. Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001–2020. Bull World Health Organ. 2017

Researchers – Beware of Predators

A recent column in Nature draws attention to ‘predatory journals’ – journals that charge open access publication fees without editorial or publishing services (such as peer-review) that are usually seen with legitimate journals.[1] Anecdotally, researchers have found that, after submitting a manuscript, they are presented with a hitherto unmentioned charge for publishing, and then when refusing to pay find that the paper is still ‘published’, making it much more difficult for it to published in another, legitimate, journal. Further, they were then invoiced for a retraction fee to remove the paper. Others have found that they have been listed on a journal’s editorial board without their explicit consent.

Although many researchers may feel that they would not fall for a predatory journal, it is still possible, especially for those who are early career researchers, those who have had a string of rejections and are feeling pressurised to publish, or those who are distracted by other concerns. Fortunately Shamseer and colleagues conducted a cross-sectional comparison study of nearly 300 journals to discern if there were any characteristics more strongly associated with predatory journals.[2] They identified 13 such characteristics that are more likely to be seen:

  1. Including biomedical and non-biomedical subjects in their scope of interest, and in particular subjects with little overlap.
  2. Having spelling and grammar errors.
  3. Using unauthorised and/or low-resolution images.
  4. Using language on the website that targets authors as opposed to readers. For example, focusing on inviting submissions, promoting metrics, etc. as opposed to highlighting recent publications.
  5. Promoting the Index Copernicus Value as a metric.
  6. Lacking description of the manuscript handling process.
  7. Requesting that manuscripts are submitted through email, as opposed to through a submission system. This often ignores requirements such as conflicts of interest declarations, funding statements, etc.
  8. Promising rapid publication.
  9. Having no retraction policy.
  10. Having no detail on digital preservation.
  11. Having low publishing fee (e.g. <$150, as opposed to >$2000 in legitimate journals).
  12. If the journal claims to be open access, either retains copyright, or fails to mention it.
  13. Having a non-professional or non-journal affiliated email address as a point of contact.

Of course, having one or some of these characteristics does not mean the journal is predatory, but should indicate that you take a closer look.

— Peter Chilton, Research Fellow


  1. Cobey K. Illegitimate journals scam even senior scientists. Nature. 6 September 2017.
  2. Shamseer L, Moher D, Maduekwe O, et al. Potential predatory and legitimate biomedical journals: can you tell the difference? A cross-sectional comparison. BMC Medicine. 2017; 15: 28.

Class Lectures in Medical School – Nearly Obsolete?

The University of Vermont’s College of Medicine advertises “no lectures required.” And empirical enquires show that context heavy, PowerPoint loaded, lectures are ineffective. But a thoughtful article in the New England Journal of Medicine [1] suggests that the class lecture should change rather than go. In fact, the classroom is well suited to active learning, with students who have already assimilated the core material at their own pace through private study. The lecturer interacts with the students who sit around tables and are provided with opportunities to discuss issues in small groups as the need arises. I learned that this is called the ‘flipped-classroom’ approach. Such an approach resulted in better outcomes when compared to traditional problem-based learning approaches in a randomised trial.[2] So a little bit of this and a little bit of that. And there is still a place for a little theatre. As to problem-based learning as a method to propel a new topic – forget it. It is sub-optimal, as discussed in a previous News Blog.[3]

— Richard Lilford, CLAHRC WM Director


  1. Schwartztein RM & Roberts DH. Saying Goodbye to Lectures in Medical School – Paradigm Shift or Passing Fad? N Engl J Med. 2017; 377(7): 605-7.
  2. Krupat E, Richards JB, Sullivan AM, Fleenor TJ Jr, Schwartzstein RM. Assessing the effectiveness of case-based collaborative learning via randomized controlled trial. Acad Med. 2016; 91: 723-9.
  3. Lilford RJ. Bring Back the University Lecture: More on Evidence-Based Teaching. NIHR CLAHRC West Midlands News Blog. 26 September 2016.

Update on Ratios of Patients to Qualified Nurses

News Blog readers may know that there is a considerable literature on nursing skill mix and patient outcomes in hospital. One of the most important studies is Paul Shekelle’s masterful systematic review from 2013.[1] Taken in the round, the literature shows a consistent association between the ratio of skilled nurses to patients and improved outcomes. A recent large cross-sectional study from a number of European countries reaches similar conclusions [2]; many outcomes of hospital care (including death rates) were improved in association with high levels of qualified nurses. Mortality reduction in hospitals with a favourable ratio of qualified nurses to patients were about 10% lower than in those with a less favourable ratio. An interesting question relates to what nurses do that could make such a large difference. An obvious mediating factor would be vigilance in recording vital signs and responding appropriately to signs of deteriorating physiology. Managing new technology, such as infusion equipment, may also be important. Getting the right medicine into the right patient at the right time is yet a further way good nursing could improve outcomes. Improved ratios are also strongly associated with patient satisfaction. Reassurance and tender care may mediate better physical outcomes given the close interplay between the nervous and immune systems.[3] These, and other, causal pathways are represented in the figure.

086 DCi - Update on Patient to Qualified Nurse Ratios

The above study did not look at process variables that might mediate a beneficial impact on nursing time. However, given  plausible mechanisms by which nurses may improve outcomes and consistent, albeit non-experimental, evidence it is not unreasonable to conclude that improving the ratio of qualified nurses to patients will improve care. Saving money by skill substitution is therefore likely to be a false economy since health economic models are sensitive to quite modest reductions in adverse events.[4]

 — Richard Lilford, CLAHRC WM Director


  1. Shekelle PG. Nurse-patient ratios as a patient safety strategy: a systematic review. Ann Intern Med. 2013; 158(5 Pt 2): 404-9.
  2. Aiken LH, Sloane D, Griffiths P, et al. Nursing skill mix in European hospitals: cross-sectional study of the association with mortality, patient ratings, and quality of care. BMJ Qual Saf. 2017; 26(7): 559-68.
  3. Lilford RJ. Brain Activity and Heart Disease – a New Mechanism. NIHR CLAHRC West Midlands News Blog. 9 June 2017.
  4. Lilford RJ, Chilton PJ, Hemming K, Girling AJ, Taylor CA, Barach P. Evaluating policy and service interventions: framework to guide selection and interpretation of study end points. BMJ. 2010; 341: c4413.

Discontinuities in Data – a Neat Statistical Method to Detect Distorted Reporting in Response to Incentives

Discontinuities can be very revealing in Service Delivery and Policy Research – they provide a statistical method to detect the distorting effects of incentives. For example, the statistical test for p-hacking reported previously in your News Blog,[1] is based around the p<0.05 threshold for statistical significance. While the p-value is easily ‘hacked’ by selectively reporting ‘significant’ results, other data may be harder – death rates for example.

The great American economist Raymond Fisman (he of the New York traffic violations fame)[2] and Yongxiang Wang examined industrial deaths in China.[3] A threshold for such deaths was set at national level, with a penalty for Provincial administrations who failed to reach the target threshold. The distribution of deaths across provinces looked like this before the incentives went live:

085 DCii Discontinuities in Data Fig 1

After the incentive, it looked like this:

085 DCii Discontinuities in Data Fig 2

Not only that, but this discontinuity is found exclusively in reports from the fourth quarter of the year. This makes a compelling case – if you provide a target and managers do not think it is fair, then they will manipulate it, even if it is something that, on the face of it, is hard to manipulate. You would not succumb to such a temptation, do I hear you say? But you would, oh yes, you would!

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Look out for ‘p-hacking’. NIHR CLAHRC West Midlands News Blog. 11 September 2015.
  2. Fisman R, Miguel E. Cultures of Corruption: Evidence from Diplomatic Parking Tickets. NBER Working Paper No. 12312. 2006.
  3. Fisman R & Wang Y. The Distortionary Effects of Incentives in Government: Evidence from China’s “Death Ceiling” Program. Am Econ J Appl Econ. 2017; 9(2): 202-18.

NICE Goes to the USA After All

Someone once said that you could always trust America to do the right thing – after they have tried everything else.[1] So at last, legislation has been passed in New York to implement value-based pricing for their States’ Medicaid programme (6m beneficiaries!). For the details, read an interesting article in JAMA.[2]

— Richard Lilford, CLAHRC WM Director


  1. Quote Investigator. Americans Will Always Do the Right Thing — After Exhausting All the Alternatives. 11 November 2012.
  2. Hwang TJ, Kesselheim AS, Sarpatwari A. Value-Based Pricing and State Reform of Prescription Drug Costs. JAMA. 2017; 318(7): 609-10.

“A Canary in the Coal Mine for Male Health”

For the past two decades, at least, there have been concerns over declining sperm count. This is an important public health issue for a number of reasons. While low sperm count is only loosely correlated with male infertility, it has also been shown to be associated with all-cause mortality, morbidity, testicular cancer and various other disorders.

Levine and colleagues conducted a meta-analysis of 185 studies covering 38 years, which looked at the semen of 42,935 men in total.[1] Adjusted meta-regression analysis showed that the sperm concentration of semen had declined significantly between 1973 and 2011 (slope of -0.64, 95% CI -1.06 to -0.22, p=0.003). On average, the mean sperm concentration had declined by 0.75% per year, with an overall drop of 28.4% since 1973. Sub-group analysis found significant decline among both unselected men (who were not selected by whether they were fertile or not, such as in screening for military service) and fertile men (who were known to have conceived a pregnancy) from Western countries (North America, Europe, Australia and New Zealand). The drop was most pronounced in unselected Western men who had declined by 1.5% per year, with an overall drop of 52.4%.

The results for all men, as well as the sub-groups, were similar when the analysis was repeated using studies conducted post-1995, suggesting that the decline was not ‘levelling off’.

Numerous factors have been suggested for contributing to such a decline, with studies showing plausible associations between sperm count and environmental oestrogens, pesticides, heat, and lifestyle factors, such as diet, stress, smoking and BMI. The authors suggest that a declining sperm count may be “a canary in the coal mine” for male health – and there is a pressing need for further research into its causes.

085 DCv A Canary in the Coalmine for Male Health Figure 1

— Peter Chilton, Research Fellow


  1. Levine H, Jørgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017; 1-14.

How Much Fruit and Veg is Enough?

We are often told that we should be eating five (or is it now ten?) portions of fruit and vegetables each day to protect against, amongst other things, cardiovascular disease (CVD).[1] However, such recommendations are generally based on research conducted in people from Europe, the USA, Japan and China. There is little data from countries in the Middle East, South America, Africa or South Asia.

The PURE study (Prospective Urban Rural Epidemiology) set out to rectify this, recruiting 135,000 participants from 18 countries, ranging from high-income countries, such as Sweden, to low-income countries, such as India.[2] The research team documented the diet of these individuals at baseline (using questionnaires specific to each country), then followed them up for a median of 7.4 years, looking at cardiovascular-related clinical outcomes. As expected higher intakes of fruit, vegetables and legumes were associated with lower incidences of major CVD, myocardial infarction, and mortality (cardiovascular-related and all-cause). However, the hazard ratio for all-cause mortality was lowest for three to four servings (375-400g) per day (0.78, 95%CI 0.69-0.88), with no significant decrease with higher consumption.

It is more likely that consuming around 375g of fruit/vegetables/legumes per day will be within the financial reach of people living in poorer countries, compared to the various recommendations of 400-800g that are often seen in Europe and North America. Before we ditch that extra snack of carrot sticks, however, it is important to note that factors such as food type, nutritional quality, cultivation and preparation are likely to vary between countries, while other clinical outcomes, such as cancer, were not looked at in this study.

The authors are continuing to enrol more participants, and are hoping to re-examine their results in the future.

— Peter Chilton, Research Fellow


  1. Oyebode O, Gordon-Dseagu V, Walker A, Mindell JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health. 2014; 68(9): 856-62.
  2. Miller V, Mente A, Dehghen M, et al. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study. Lancet. 2017.

Should You Keep Drinking Coffee?

It is nice, at last, to find something that is it is really enjoyable and that is good for us. Recent News Blogs have carried articles on the harmful effects of red meat,[1] milk,[2] and alcohol.[3] But what about coffee? A recent article, based on over 500,000 people in ten European countries confirmed the already extensive literature showing that coffee is beneficial for health.[4] In fact, overall death rates were reduced by over 10%. There was a massive (over 50%) reduction in diseases of the digestive system, confirming the well-known beneficial effect of coffee on the liver. The trend was also favourable for heart disease and stroke. Many biochemical markers also moved in a favourable direction, including glycated haemoglobin, and C-reactive protein. The only bit of bad news pertained to ovarian cancer, where a 30% increased risk of death was noted. Reverse causality is always a possibility in non-experimental studies, even if, like this one, they are prospective. However, this is unlikely since the hazard ratios were unaltered if patients who died within eight years of recruitment were excluded.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. An Issue of BMJ with Multiple Studies on Diet. NIHR CLAHRC West Midlands News Blog. 4 August 2017.
  2. Lilford RJ. Two Provocative Papers on Diet and Health. NIHR CLAHRC West Midlands News Blog. 12 December 2014.
  3. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August 2017.
  4. Gunter MJ, Murphy N, Cross AJ, et al. Coffee Drinking and Mortality in 10 European Countries. Ann Intern Med. 2017; 167: 236-47.