Trachea transplants and awful articulation: doing the BMJ podcast

Last week my colleague Sally Carter and I had a go at doing the news roundup for the BMJ podcast.

First, Sally spoke about the passing of the health reform bill in the US and all the BMJ‘s coverage of the legislation itself and the bill’s rocky passage. Then I covered a remarkable news story about a British boy who received fledgling trachea transplant built with his own stem cells that then grew into a fully functioning organ within his body.

I’ve always had trouble with public speaking and being articulate during presentations, so I was very nervous about doing my first podcast.  Despite our countless rehearsals, Sally and I both found it quite hard to simultaneously speak fluently and get all the facts into our segments.  The experience was a lot of fun though and I think the finished product turned out OK.  Have a listen and let me know what you think.

BMJ Podcast 26 March 2010: Variolae Vaccina

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Keep your eyes on your kids in the laundry room – for the sake of theirs

Liquid detergent tabDon’t leave your young kids unsupervised with your laundry. Not just because they might start mixing with your carefully separated piles of whites and darks, but because they might injure their eyes playing with the brightly coloured liquid detergent capsules.

A letter to the BMJ, ophthalmologists at the Western Eye Hospital in London have highlighted a “wave of paediatric eye injuries” from liquid capsules for fabric detergents. These capsules were responsible for 40% of chemical eye injuries in children under the age of 5 last year at the hospital.

The majority of the 13 children who presented to the hospital with such injuries were girls. In 12 cases the kids were fine after treatment, but one child only had their eyes washed on arrival and sustained permanent burns on both their eyes.

Furthermore, the Poisons Unit at Guy’s and St Thomas’ hospital, also in London, received 192 enquires related to the capsules during 2007-8 and 225 calls during 2006-7, a fifth of which related to ocular exposure.

Liquid detergent capsules, also known as liquitabs, were first introduced in 2001 and are composed of an alkaline solution contained in a water soluble membrane that dissolves when in contact with moist hands or the mouth. Alkali injuries are the most severe form of chemical eye injury and can cause irreversible damage.

The authors advise that concentrated cleaning products like liquitabs should be kept out of the reach of children. If an accident occurs, parents should immediately wash their child’s eyes to reduce the chance that their child will suffer permanent eye damage.

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Medical school entrance exam favours white public school boys

Exam hallNew research has found that the UK Clinical Aptitude Test (UKCAT), introduced to level the playing field in selection for medical and dental schools, favours male applicants, white people, and students from a higher socioeconomic class or who attended an independent or grammar school.

In the UK, students take advanced level (A level) exams aged 18, and it is the grades they get in these exams that primarily determine whether they can secure a place at university. A levels are affected by socioeconomic bias though – students who are academically able but whose education has been compromised by attending a bad school can end up performing badly and miss out on a place.

The UKCAT, however, doesn’t examine acquired knowledge and candidates can’t be “coached” to pass, so in theory it should provide a more fair assessment of aptitude than A level grades.

In addition, medical school selectors aren’t just interested in academic ability – they want to pick out students who have the personality attributes that will make them a good doctor, like excellent interpersonal skills and professional integrity.

The various components of the UKCAT – verbal reasoning, quantitative reasoning, abstract reasoning, and decision making – are supposed to be best measures to pick out such traits, so the test should also help determine the students who have the personality attributes to make a great doctor.

Unfortunately, the research by James et al, published in the BMJ, suggests that the UKCAT doesn’t really provide a more “equitable assessment of aptitude” than A levels.

The authors looked at data from applicants to 23 UK medical schools who took the UKCAT in 2006, the year it was first introduced. People who sat the test were asked to supply demographic and socioeconomic data such as their parents’ or carers’ occupation. The UKCAT data was then compared with A level results, the current “gold standard” in selection.

From the 18,582 individuals who took the UKCAT in 2006, the authors identified a subgroup of 9884 (53%) students who lived in the UK and for whom they had results data on at least three recent A levels. There was a modest correlation between A level grades and UKCAT scores, which indicates that the test could be used as an alternative to A level grades in the selection process

As far as bias in A level results went, sex didn’t have much of an effect on whether a student scored AAA or AAB – the minimum requirement for medical school admission. However, white students and those whose parents had a managerial or professional job were more likely to get top scores.

Startlingly, applicants who went to an independent or grammar school were more than twice as likely to get top A level grades than those who went to a comprehensive school, sixth form college, or some other sort of higher education institution.

The UKCAT was slightly less subject to socioeconomic bias than A level results. However, male applicants were more likely to get a high score (i.e. a score within the top 30% out of all applicants) than were females. White students were twice as likely to get a high score than students in other ethnic groups, and “professional or managerial background” and “independent or grammar schooling” were likewise independent predictors of a top score.

So although the test is less biased than A levels, the UKCAT still has “an inherent favourable bias to male applicants and those from a higher socioeconomic class or from independent or grammar schools,” conclude the authors.

One major limitation of the study is that about 30% of participants did not provide socioeconomic data when they sat the UKCAT, so a considerable proportion of applicants covered in the A levels calculations were excluded from the UKCAT analyses. Those who withheld socioeconomic status data were more likely to be male, non-white, and from non-selective schools, and were less likely to have top A levels grades and high UKCAT scores. “Arguably, this group contained those candidates who were more likely to benefit from widening participation,” say the authors.

In a rapid response to the research, Rachel Greatrix, chief operating officer of UKCAT, rather unexpectedly welcomes the findings. “It is reassuring that medical and dental schools can use the test as a reasonable proxy for A levels given the on-going debate regarding the speculative nature of predicted grades and discussions regarding post-qualification admissions,” she says. “However, the fact that UKCAT scores are less subject to bias than A level results alone, potentially indicates that if combined with A level achievement, they may offer a fairer tool for selection.”

James D, Yates J, & Nicholson S (2010) Comparison of A level and UKCAT performance in students applying to UK medical and dental schools in 2006: cohort study. BMJ 340 (feb16 1). DOI: 10.1136/bmj.c478

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Tamiflu isn’t much good and Roche tried to stop us showing so, says the BMJ

The BMJ has just published a whole slew of papers about Tamiflu (oseltamivir) – a key drug in the public health response against swine flu (influenza A/H1N1).

The linchpin is a Cochrane review on the efficacy of neuraminidase inhibitors – namely zanamivir (Relenza; Glaxo Wellcome) and oseltamivir (Tamiflu; Roche) – for preventing and treating influenza in healthy adults.  The review found that these two drugs were only partly effective against laboratory confirmed symptomatic influenza (oseltamivir 61% effective; zanamivir 62% effective), and no good at all against asymptomatic flu or flu-like illness.

In addition, Tamiflu did not reduce the risk of influenza-related lower respiratory tract complications – bad news for the Department of Health, which recommends using the drug to prevent secondary complications in healthy adults.  The authors conclude: “Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza.”

In an accompanying feature, Deborah Cohen retraces the steps leading to the publication of the Cochrane review and highlights all the difficulties the authors had extracting data from Roche, the makers of Tamiflu.  The review “exposed a complex interplay between politics, public health planning, availability of trial data, publishing, and drug regulation.”

Turns out that Roche’s claims that Tamiflu reduces hospital admissions and secondary complications of influenza were based on a 2003 meta-analysis that only included two proper randomised controlled trials and was authored by several Roche employees.  When the authors of the Cochrane review tried to get their hands on the data in this paper to include them in their own analysis, they came up against all sorts of obstacles thrown up by Roche.

Peter Doshi, an author of the new Cochrane review, writes in the BMJ of his struggle to get hold of the elusive data and offers a damning verdict on the use of the drug in the swine flu epidemic. “Since August 2009, our Cochrane review team has tried to obtain the data needed to verify claims that oseltamivir (Tamiflu) lowers serious complications of influenza such as pneumonia. We failed, but in failing discovered that the public evidence base for this global public health drug is fragmented, inconsistent, and contradictory. We are no longer sure that oseltamivir offers a therapeutic and public health policy advantage over cheap, over the counter drugs such as aspirin.”

In an analysis article, Nick Freemantle and Mel Calvert look over the observational studies of Tamiflu that Roche cited in defense of their claims for the drug and found that they also do not support the use of Tamiflu to treat influenza in healthy adults. In their discussion they write: “oseltamivir may reduce the risk of pneumonia in otherwise healthy people who contract flu. However, the absolute benefit is small, and side effects and safety should also be considered. None of the studies examined the role of oseltamivir in patients with H1N1 influenza, which may be associated with higher rates of pneumonitis than seasonal influenza.”

Finally, in a linked editorial, Fiona Godlee, editor of the BMJ, and Mike Clarke, director of the UK Cochrane Centre in Oxford, rail against the obstructive techniques used by Roche and call for full data from clinical trials to be made available to the scientific community.  “Why should the public have to rely on detective work by academics and journalists to patch together the evidence on such a potentially important drug?” they ask.

All this is bad news for public health planning against swine flu – the Department of Health has already stockpiled more than 30 million doses of potentially useless Tamiflu – and even worse news for Roche.

Jefferson T, Jones M, Doshi P, & Del Mar C (2009) Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ 339 DOI: 10.1136/bmj.b5106

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Festive funnies in the BMJ Christmas issue

Christmas treeEvery year the British Medical Journal team get in the festive spirit with their Christmas issue, publishing zany or amusing research.  This year is no exception, with a host of genuine research papers and rigorous scientific analyses guaranteed to make you giggle.

Research articles in this week’s issue of BMJ include:

  • Head bangers: stuck between rock and a hard bass
  • Head banging to heavy metal is a popular dance form, but it increases the risk of head and neck injury. The effects may be lessened with reduced head and neck motion, head banging to lower tempo songs or to every second beat, and using protective equipment such as neck braces, say Australian researchers Declan Patton and Andrew McIntosh.

  • Rugby (the religion of Wales) and its influence on the Catholic church: should Pope Benedict XVI be worried?
  • Researcher Gareth Payne and his two colleagues from Cardiff investigate whether there is any substance to the intriguing urban legend that has arisen in Wales in recent times: “Every time Wales win the rugby grand slam, a Pope dies, except for 1978 when Wales were really good, and two Popes died.” Wales won the Grand Slam in 2008 – so should Pope Benedict XVI be worried?

  • Frankincense: systematic review
  • Edzard Ernst, the UK’s only professor of complementary medicine, systematically reviews the evidence on frankincense – a tree resin that was one of the first ever Christmas presents and is now a popular complementary remedy. He concludes that, although frankincense does not bestow supernatural instant youth or eternal life as many claims would have it, it has encouraging anti-inflammatory properties.

In the comment section, Deborah J Anderson, an author of the IgNobel-winning research on the use of coca cola as a spermicide, advises against this approach to contraception, while MA Buchanan and colleagues discuss whether modern golf clubs can cause hearing damage.

The Christmas issue also traditionally subjects prevalent medical myths to critical appraisal.  Last year Rachel Vreeman and Aaron Carroll showed that reading in low light does not damage eyesight and that turkey is not to blame for drowsiness after Christmas dinner.  This year they turn their attention to whether sugar causes hyperactivity in children and if wearing a hat reduces heat loss in cold weather, thoroughly debunking these popular beliefs.

The whole BMJ Christmas issue can be found online at  I hope you enjoy it as much as I did!

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Are researchers fudging clinical trial statistics?

Before a clinical trial can commence a protocol – a plan of exactly how a trial will be conducted – will be formulated.  As part of the planning, the individuals undertaking the trial will calculate approximately how many patients need to take part for the results to be meaningful (the ‘sample size’) and prespecify which statistical tests they will perform on the data once the trial is complete.

A new study of published clinical trials, however, has found that many do not report these crucial sample-size calculations and that authors often do not mention if they have changed their mind as to which statistical test they are going to use.  About half of the trials studied by Chan et al. did not include sample-size calculations or mention whether the statistical tests actually used on the data differed from those provided in the trial protocol.

It is important that people conducting clinical trials stick to the statistical methods outlined in their protocol, as different types of statistical test can produce different outcomes for the same set of raw data.  If trial authors plan to use a particular test then change their mind and use a different test once they have seen the data, the results can be inadvertently biased – or directly manipulated – so they appear much more positive.

In the recent BMJ study, Chan et al. compared the published papers of 70 Danish randomized clinical trials with the corresponding protocols, which had been submitted to the local ethics committees for approval before the trials commenced.

Only 11 trials fully and consistently described sample-size calculations in both the protocol and the published paper. There were unacknowledged discrepancies between the calculations in the protocol and those in the published paper in 53% of cases.

Most protocols and publications specified which statistical tests would be used on the trial data; however, in 60-100% of cases the tests listed in the published paper differed from those in the protocol.

So it seems that in many cases sample size calculations and statistical methods are not prespecified in trial protocols or are poorly reported.  If they are prespecified, authors don’t tend to acknowledge instances when the statistical methods used differ from those in the protocol.  These two practices can easily introduce bias into the analysis of clinical trials and, ultimately, lead to misinterpretation of study results.

All this is bad news for everyone – if trial results aren’t reported honestly and transparently then it will be impossible to tell which trials, and therefore treatments, will genuinely help patients.  Hopefully initiatives such as SPIRIT (Standard Protocol Items for Randomised Trials), launched by Chan et al., and CONSORT (Consolidated Standards of Reporting Trials) will improve the accuracy of clinical trial reporting, but always remember: “There are three kinds of lies: lies, damned lies, and statistics”.

Chan AW et al. (2008) Discrepancies in sample size calculations and data analyses reported in randomised trials: comparison of publications with protocols BMJ 337 (4 Dec 2008) DOI: 10.1136/bmj.a2299

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