New genetic test to decide treatment for difficult childhood asthma

Researchers in Dundee and Brighton have reported in the journal Clinical Science a randomised study using gene testing aimed at improving treatment selection in children with asthma.
The gene variant (Arg16 genotype) they tested has previously been reported to be associated with failure to respond to commonly used beta-2 agonist bronchodilator inhaler treatment.
My comments below on the potential and limitations of the study were included in a briefing by the Science Media Centre.

Prof Donald Singer, Member of the British Pharmacological Society and Professor of Clinical Pharmacology and Therapeutics at the University of Warwick, said:
“This study is important in providing evidence that simple genetic testing can be used to personalize selection of medicine in clinical practice – in this case applied to treatment choice in children with poorly controlled asthma.
“Their main outcome – less time off school because of asthma – is important both for children and their families. The authors were careful to consider poor compliance with asthma treatment as an important alternative explanation for their findings. However this is a small study and needs to be confirmed in larger well-controlled clinical trials.”

Research paper:
Tailored second-line therapy in asthmatic children with the Arg16 genotype.  Lipworth BJ et al., published in Clinical Science on Tuesday 8^th January 2013.

Favourite poems with a medical theme - 2013

To mark the 2013 International Hippocrates Prize for Poetry and Medicine, the organisers invite nominations of your favourite poem with a medical theme.

'Medical' is to be interpreted in the broadest sense. Nominations may be from anyone anywhere in the world and for poems written by a poet from anywhere in the world and in any language. The poem may to be contemporary or from any historical period.

You can see examples at 'favourite poems on a medical theme' of comments received and find links to many of the nominated favourite poems in 2012.

And some recent nominations:

John Betjeman - 'Before Anaesthetic ...'

Nazim Hikmet - 'Angina Pectoris' 

...

The Hippocrates Prize of £5000 for the winning poem in both the Open International and the UK NHS category is one of the highest value awards in the world for an unpublished poem in English on a medical theme.

There is also a new Hippocrate Prize of £500 for Young Poets aged 14 - 18 years, from anywhere in the world.

Awards for the 2013 Hippocrates Prize will be presented by the judges on Saturday 18th May 2012 at the  4th International Symposium on Poetry and Medicine, to be held at the Wellcome Collection in London.

Closing dates for 2013 Hippocrates Prize for Poetry and Medicine
Open International category - 31st January, 2013
NHS UK category - 31st January, 2013
Young Poets category - 1st March, 2013

Key 2013 dates and deadlines for the Hippocrates Initiative for Poetry and Medicine

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The Hippocrates Prize for Poetry and Medicine is an annual international award for an unpublished poem on a medical subject. With a 1st prize for the winning poem in both the Open International and the NHS category of £5,000, the Hippocrates prize is one of the highest value poetry awards in the world for a single poem.

Since its launch in 2009, the Hippocrates Prize has attracted over 4000 entries from 44 countries, from the Americas to Fiji and Finland to Australasia.

Awards are in 3 categories: 

- an Open category, which anyone in the world may enter; 

- an NHS category, which is open to UK National Health Service employees, health students and those working in professional organisations involved in education and training of NHS students and staff.

- a category for Young Poets aged 14 - 18 years

1st Feb 5pm GMT deadline for the Hippocrates Prize for Poetry and Medicine
The 2013 Hippocrates Prize for Poetry and Medicine  has a  £5000 1st prize both in a UK NHS category and an Open International category.  Judges are poet Jo Shapcott, science writer and Science Museums Director Roger Highfield, and medical doctor and writer Theodore Dalrymple.

There have been entries to date for 2013 Hippocrates awards from 16 countries in North America, Europe, Africa, South Asia and Australasia.

The Hippocrates Prize is for unpublished poems in English on a medical theme, up to 50 lines, in addition to the title and lines between verses.
Entries are online.

1st March deadline for the Hippocrates Prize for Young Poets
Also two months until the 1st March 2013 deadline for the new Hippocrates Prize for Young Poets which has a £500 1st prize.

The Hippocrates Prize for Young Poets - judged by poet Claire Pollard - is for unpublished poems in English on a medical theme, up to 50 lines, in addition to the title and lines between verses.

For the Hippocrates Prize for Young Poets  entries are online and poets should be aged 14 to 18 years old on the 1st March 2013 submission deadline. Entries for this new prize may either be made by individual young poets, or on their behalf by parents, schools or colleges.

Palazzo Ca' Pesaro Papafava in the heart of Venice

Saturday 21st - Sunday 22nd September 2013, Venice: Hippocrates workshop on Poetry and Medicine 
The Hippocrates in Venice workshop will consist of lectures, breakout sessions, round table discussions on the interface between poetry and medicine, both from a humanities perspective and from the perspectives of health professionals, patients and poets.
The venue is the 15th Century Palazzo Ca' Pesaro Papafava in the heart of old Venice, Italy.
To express interest in attending, email the organisers.

Saturday 18th May 2013, London: International Symposium on Poetry and Medicine
The Symposium will take place at the Wellcome Collection rooms in London. Abstract submission and registration is currently open for the symposium, which will include poster sessions, lectures, round table discussions and poetry readings by 2013 Hippocrates Awards judge: poet Jo Shapcott. There will be sessions on historical and contemporary themes, illness and poetry, poetry as therapy, poetry in the education of medical students, nurses and doctors, and poetry as an aid to health professionals.

Wellcome Collection, London

The programme of lectures, round table discussions, poetry readings and the Hippocrates Awards Ceremony will be published on the Symposium website. The winners and commended entrants will be announced by the judges at the end of the 4th International Symposium on Poetry and Medicine.

The 2013 Symposium Faculty includes: Theodore Dalrymple (Doctor and writer; 2013 Hippocrates Prize Judging Panel); Michael Hulse (Speaker and Chair; Writing Programme, Warwick):Roger Highfield (Director of External Affairs, Science Museum Group, London: 2013 Hippocrates Prize Judging Panel); Anne Hudson Jones (Speaker: Harris L Kempner Professor in Humanities in Medicine, University of Texas Medical Branch, Galveston); Hugues Marchal (Speaker: Professor of Modern and Contemporary Literature, Basel University, Switzerland); Femi Oyebode (Psychiatrist, University of Birmingham); Jo Shapcott (Poet, Royal Holloway College, London; 2013 Hippocrates Prize Judging Panel); Donald Singer (Speaker and Chair; Warwick Medical School).

L'Amour, carotid and stroke

As cinema, Michael Haneke's l'Amour is a human drama about the effect of illness on family (partner and next generation), the reality of managing a progressively failing spouse at home, challenges of involving carers, perspectives of young protégé, of emergency services, of remote relatives ...
A subtext is personalising the question:why stroke(s) in this slim elderly woman, the mystery of the transient cerebral ischaemic attack - micro-emboli? transient local clot on a narrow artery? ...
And the human impact of the dilemma:what to do about severe carotid disease and minimising risk of surgery?

See recent blog on predicting and suppressing cerebral micro-emboli in patients with carotid disease.

Sleeping pills and risk of pneumonia

Research published in the journal Thorax has suggested that commonly prescribed sleeping tablets - benzodiazepines - are linked to increased risk of pneumonia, and to risk of 30 day and longer term mortality in patients diagnosed as having had community acquired pneumonia.  Reasons are unclear however these medicines may both impair immune responses and reduce the depth of breathing, thus making it more difficult for microbes to be cleared from the lungs. Reported risk of pneumonia was more evident with longer term use of sleeping tablets. 

Of note, this was a case control  study and thus at much greater risk of inadvertent bias as a reason for the findings than more reliable double blind, randomised controlled trials. It would be expected that patients with greater overall disease burden would be at higher risk of pneumonia if the relationship with treatment were due to 'cause and effect'. However the reverse was reported by the study authors. 

This work suggests the need for further studies to explore these potential risks in more detail. 
Meantime, there are risks to stopping these medicines suddenly. Patients with concerns should contact their medical advisor or pharmacist for advice. 

The original study

Expert comment

Media reporting

Progress on Personalized Medicine? Updates from Harvard.

@HealthMed The 8th annual Personalized Medicine Conference took place at Harvard this week - a joint venture of Harvard Medical School, Harvard Business School and Partners Healthcare, lead by Professor Raju Kucherlapati, from the HMS Department of Genetics. Worth checking the excellent archive of past programmes, presentations and podcasts.
Meantime, some of the highlights?
- An excellent narrative on the partnership between Plexxikon (Peter Hirth) and Roche Diagnostics (Suzanne Cheng) to create a companion diagnostic/therapeutic pairing for vemurafenib (Zelboraf), the first FDA approved pairing for BRAF V600E positive metastatic melanoma
- Further case studies illustrating successful drug development using genetic approaches
- Personal case studies on the impact, clinical value and ethical and clinical challenges of genomic screening: from Joe Beery, Life Technologies, on detecting unrecognised treatable serious early childhood disorders, to John Lauerman, Bloomberg News, on consequences of sequencing for asymptomatic adults - questions on penetrance and future screening for onset e.g.  of metabolic disease and cancers

Harvard Medical School: New Research Building - Avenue Pasteur.

- Clinical potential, and regulatory and reimbursement challenges to introducing molecular diagnostics into clinical care pathways
- Leadership award to Randy Scott, In Vitae, whose discussion points included the relevance of Moore's Law (technology advancing) and Metcalfe's Law (people factors: exponential increase in interaction as network expands) to developments in personalized medicine
- Business models and their governance for use of genetic information
- A North Virginia (John Vockley, Inova) pioneering series of projects aiming to assess outcomes of neonatal genomic sequencing: from insight into preterm labour to prospective longitudinal follow-up to adulthood, supported by multi-generation family member sequencing combined with clinical histories
- The US Air Force Programme on Patient-Centered Precision Care (Dr Cecili Sessions), in partnership with the Coriell Institute and Johns Hopkins University,  aims of which include understanding the impact on health-related behaviour of providing personal genetic information on remediable medical disorders and on drug responses.
- A business school case study led by Professor Richard Hamermesh, Director of the HBS HealthCare Initiative, on reactive and proactive responses for development of companion diagnostics (1).
- Pros and cons of liberal vs. restrictive approaches to IP for genetic and other molecular diagnostics
- Engaging the policy community and the public in ethical, clinical, reimbursement and adoption issues for new diagnostics and treatments aimed at personalizing medicine, including case studies from the American Medical Association and the American Assocation for Cancer Research.

Personalized Medicine Conference website 
Companion and coupled diagnostics

Boris Godunov

Boris Godunov

@HealthMed The RSC is currently running a new version by Adrien Mitchell of Pushkin's Boris Godunov - in which Godunov is accused of the murder of the young epileptic son of former Tsar Ivan the Terrible, following which he (Godunov) allows himself to be 'persuaded' to became the new Tsar. 

Tsar of Russia Boris Godunov is said to have died in mid-April 1605 after a lengthy illness, the cause of death attributed to a stroke. 

Hippocrates is considered to have been the earliest to describe stroke - then called apoplexy [for Gk for to strike down/incapacitate]. As insight into Roman views on the cause of apoplexy, the Latin translation (sideratio) indicates a disease caused by a constellation.  It wasn't until several decades after Godunov's death that Swiss pharmacologist and pathologist Johann Jakob Wepfer linked apoplexy both to bleeding within the brain and to blockage of a blood vessel in the brain. His work on strokes was published in 1658 as Historiae apoplecticorum. 

Depicted as well-fed, Godunov by the age of 54 would have been at risk of hypertension, diabetes and hyperlipidaemia. Other causes of apoplexy could have included a primary or secondary cerebral tumour, indolent brain infection/abscess such as tuberculosis, or indeed a ruptured congenital vascular anomaly. Poisoning was of course then an occupational hazard. Slow onset heavy metal or other toxins could have contributed to his reported long terminal illness.

Apoplexy has attracted fascination from historical reports (e.g. from Petrarch to Copernicus and Catherine the Great, surgeon John Hunter's suspected caused of death - reportedly during a meeting with the board of management, and President Woodrow Wilson) to fictional references - often with a hint of retribution (e.g. Villefort's father in the Count of Monte Cristo, Rip van Winkle's wife ... ). 

For more on general aspects of apoplexy, see History of Stroke by Maurizio Paciaroni and Julien Bogousslavsky.

Shakespeare's Medicine Cabinet discussed at the Dana Centre

@HealthMed: Shakespeare’s Medicine Cabinet was the theme of a packed evening session at the Dana Centre on 8^th November. The Dana Centre is funded as joint venture with the Science Museum and Imperial College London, with the aim of bringing together the public with academics and other experts to discuss a wide range of themes.

This evening explored, with the help of the excellent Dana Actors (directed by Silvia Ayguade), facts and fantasy underlying effects of plants as medicines, poisons and aphrodisiacs in Shakespeare’s plays.

Professor Rod Flower FRS selected examples from Macbeth, Midsummer Night’s Dream and Romeo and Juliet, asking the question whether botanical references were ‘merely dramatic license, or was there a scientific basis for the use of drugs in his plays?’ For example Juliet imploring the Friar:

“… Let me have a dram of poison, such soon-speeding gear 

As will disperse itself through all the veins 

That the life-weary taker may fall dead …”

And the Friar’s offer of a specific death-mimicking toxin to last ‘… two and forty hours …’

Love-in-idleness

The interval was spiced with the opportunity provided by the British Pharmacological Society organisers to sample some of the healthier plants mentioned, including an interesting Heartsease floral tea – the plant referred to as ‘love-in-idleness' by King Oberon in Midsummer Night’s Dream.

Dr Randolph Arroo, Head of Research at the School of Pharmacy in Leicester, went on to discuss the interface between plants and medicines in the second Elizebethan Age.

His comments on reliability of plant sources and earlier issues raised by Professor Flower were echoed in the discussion points raised by a very engaged and informed audience.

For more see the Dana Centre website

and the website of co-organiser the British Pharmacological Society.