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Saturday, 10 December 2016

Adaptive pathways for evaluating medicines for serious unmet medical need: the access v. evidence dilemma

The European Medicines Agency hosted a stakeholder workshop on 8th December 2016 on adaptive pathways at its Canary Wharf London headquarters: a hot topic with around 150 delegates from healthcare, patient and consumer organisations, academia, industry and regulatory bodies.
The European Medicines Agency organised this workshop in collaboration with the European Commission to gather views and proposals from stakeholders on the adaptive pathways approach, in light of the practical experience gained during the pilot project EMA ran between March 2014 and August 2016, and to plan the next steps in the exploration of this concept. 


The basis for considering adaptive pathways for evaluating medicines is to meet the challenges underlying how to resolve high unmet medical need with then aim of licensing products likely to have a major impact on patient morbidity and/or life expectancy.
The desire is to find ways to reduce unavoidable uncertainties as rapidly as possible for serious/rare debilitating and life-shortening illnesses. There are clear ethical and scientific challenges in using novel approaches to evaluate medicines without a decline in the quality of evidence on the effectiveness and safety of new treatments. 

Products which might be considered for use of adaptive evaluation pathways include both conventional medicines and advanced therapy medicinal products (ATMPs). ATMPs are medicinal product which involve either a gene therapy medicinal, a somatic cell therapy or a tissue engineered product [see more on ATMPs at Directive 2001/83/EC as amended by the ATMP Regulation 1394/2007].

Adaptive pathways contribute to an expanded  toolbox for evidence generation where conventional randomized controlled trials are not-appropriate or practical. Principles include using processes to allow rapid reaction to uncertainty by iterative development based on ongoing analysis of  pathway data [“rapid cycle analysis”]. As secondary end-points are welcomed, these pathways require pre-planning across the entire product life-span, including the post-marketing paths ie active monitoring and management of on-market use.

The adaptive pathway approach is dependent on earliest stage and ongoing multi-stakeholder networking, underpinned by risk management plans. 

Critical issues include
- resolving scientific trust in real world data and the need to develop mature, robust registries
- defining and prioritising unmet medical needs
- agreement on acceptable risks and benefits early access worth it (vs.
- maintaining safety standards
- ensuring that benefits outweigh risks
- avoiding unrealistic expectations
- establishing practical criteria for reimbursement, especially when secondary outcome measures form the basis for market authorization  

Tuesday, 15 November 2016

Safer Big Data for safer medicines?

14-15 November, 2016: The European Medicines Agency has invited experts from the European Union and the USA to discuss 5 key perspectives to speak on Big Data at a workshop in London aimed at identifying opportunities from 'Real World and other "Big Data" to improve development of new medicines and surveillance of licensed medicines for safety, risk and effectiveness.

The 5 key 'stakeholder' perspectives? Patients and the public, health professionals, academia, regulators and policy makers, industry (both health sector and software/hardware) and payers (considering a change in strategy to payment for health impact rather than sales, as exemplified by the Health Impact Fund).

A pragmatic definition from Lu and his colleagues states that "Big data analytics (BDA) applications are a new category of software applications that process large amounts of data using scalable parallel processing infrastructure to obtain hidden value." There are many potential applications from planning for public transport flows to using large health record datasets to improve patient safety such as in the US FDA-Harvard Sentinel partnership.

The FAIR principles for Big Data, Finding, Accessing, Interoperability and Reuse of Big Data, have both general and special challenges and potential benefits when applied to healthcare.

For example, in a recent issue of Nature Reviews Cardiology, Rumsfeld and colleagues from Colorado and Boston outline 8 potential applications of big data analytics to improve cardiovascular care, including "predictive modelling for risk and resource use, population management, drug and medical device safety surveillance, disease and treatment heterogeneity, precision medicine and clinical decision support, quality of care and performance measurement, and public health and research applications".

The EMA note: "Rapid developments in technology have led to the generation of vast volumes of data, which have the capability to transform the way the benefit-risk of medicinal products is assessed over their entire life cycle. However, it is recognised there are multiple challenges in the exploitation of these data.

"These range from the fundamental need to establish methods to enable the access to, integration and analysis of heterogeneous datasets to understanding the limitations in its use. Importantly, robust and transparent mechanisms to protect patient confidentiality are key to secure patient trust. It is important for the European Medicines Agency and the European Union medicines regulatory network to gather information on the latest developments in big data from the perspective of all stakeholders in order to identity how and when the multitude of data sources may contribute to medicinal product development, authorisation and post-marketing surveillance."

Some key themes:
- Patrick Ryan on which patients chose which treatments
- Sophie Louveaux discussing new EU regulation of data, meaningful consent and processing sensitive health data
- David Martin addressing challenges in Big Data analytics from FDA and PPP perspectives
- Julian Isla from the Dravet patient charity on making the patient the centre in digital health
- Baroness Helene Hayman on ethics, governance and public confidence
- Ronald Brand from the University of Leiden on informed consent v. opt out
- Nicolas Tatonetti from Columbia University, NY on data mining for medical discovery
- Nico Gaviola from Google on cloud data for safer medicines

See more on key threads and discussion points including on the European Open Science Cloud, new EU General Data Protection Regulations - from May 2018, replacing Directive 95/46, machine-learning for chemogenomics, challenges to implementing applications to precision medicines, access to the OHDSI community, social media to find new adverse drug event signals, FDA case studies using then Sentinel-HMO-Harvard collaboration,  opening access to the 28 EU independent national health care systems and more in due course when talks are made available on the EMA website for public access.

Tuesday, 8 November 2016

Antimicrobial resistance - a global public health threat

"Proper infection control practices and antimicrobial stewardship will be important to address this emerging threat" is the conclusion of a new publication from Sub-Saharan Africa on trends and reasons why resistance to antibiotics is becoming an increasing international problem.

The study, just published in the latest issue of the American Journal of Tropical Medicine and Hygiene, looked at data collected over a 5 year period on sensitivity of bacterial cultures to a wide range of WHO essential list as well as newer antibiotic medicines.

The data were collected in Kigali, Rwanda, at King Faisal Hospital, a major teaching and referral hospital for patients from throughout
Rwanda and from neighbouring countries.

The research team comprised international researchers from the USA (Yale AIDS Programme and the Department of Public Health, Philadelphia), the UK (Fellowship of Postgraduate Medicine, London) and SMBT Institute of Medical Science and Research Center in Nashik, India, in collaboration with clinicians from the King Faisal Hospital in Kigali, Rwanda.

"Differences in antimicrobial susceptibility between the first and fifth year of the study for each bacterial species was assessed using 2 test. Of 5,296 isolates collected, 46.7% were Escherichia coli, 18.4% were Klebsiella spp., 5.9% were Acinetobacter spp., 7.1% were Pseudomonas spp.,
11.7% were Staphylococcus aureus, and 10.3% were Enterococcus spp. Colistin and imipenem had greatest activity against gram-negative bacteria. 

Acinetobacter spp. showed the greatest resistance profile to antimicrobials tested, relative to other gram-negative bacteria. Vancomycin retained excellent activity against S. aureus and Enterococcus species (average susceptibility was 100% and 99.4%, respectively). 
Trend analysis determined that resistance to imipenem increased significantly among Klebsiella, E. coli, Pseudomonas, and Acinetobacter isolates; there was also rising resistance to colistin among E. coli and Pseudomonas species. 
Only E. coli demonstrated increased resistance to gentamicin. For gram-positive pathogens, vancomycin susceptibility increased over time for Enterococcus species, but was unchanged for S. aureus. Our data suggest that resistance to imipenem and colistin are rising among gram-negative bacteria in Rwanda."

Read the full article


Thursday, 27 October 2016

Safer medicines in children and adults: video discussions from the international 2016 EACPT Focus Meeting in Opatija



In these videos, Donald Singer discusses with speaker Suzana Mimica Matanovic evaluation of drugs in the pediatric population with an update on the impact of recent initiatives from the European Medicines Agency and discusses with Janne Backman from Helsinki how to identify and minimise risk of drug-drug interactions.


 

Discussants
- Suzana Matanovic: Assistant Professor of Clinical Pharmacology, School of Medicine, University of Osijek, Croatia and PCO alternate delegate at the European Medicines Agency
- Janne Tapio Backman: Professor in Clinical Pharmacology and Individual Medicine, University of Helsinki, Finland
- Professor Donald Singer: member of the Executive Committee of the European Association for Clinical Pharmacology and Therapeutics and EACPT delegate on the European Medicines Agency Health Professionals Working Party. 

Here is a summary of the key points from Professor Backman's  talk at the EACPT Focus Meeting in Opatija: 

Drug-drug interactions can either markedly reduce or enhance the therapeutic or adverse effects of drugs by causing alterations in the pharmacokinetics or pharmacodynamics of drugs. If such interactions are not understood or accounted for in patient care, they can have harmful, even hazardous clinical consequences. 

Drug-drug interactions have been a major cause of drug withdrawals from the market. Regulatory agencies, including the European Medicines Agency (EMA) have therefore published guidance documents that are designed for the industry to guide their DDI studies during drug development. In particular, detailed scientific recommendations can be given concerning pharmacokinetic interactions, because such interactions can be mediated via mechanistic changes in absorption, distribution, metabolism and excretion of drugs. 

Specific approaches are suggested concerning cytochrome P450 enzymes (CYPs), non-CYP enzymes and membrane transporters. In addition, current guidance also recommends use of modelling approaches, such as physiologically based pharmacokinetic (PBPK) models to design and extend the interpretation of preclinical and clinical drug-drug interaction studies. For designing clinical drug-drug interactions studies, detailed preclinical in vitro and early clinical pharmacokinetic information is necessary. 

Despite detailed guidelines, there are many challenges in characterization of the interaction potential of a drug, both as a perpetrator and as a victim of the interaction. Such challenges arise from complex interaction mechanisms, eg, simultaneous involvement of transporters and drug metabolizing enzymes, autoinhibition and autoinduction of metabolism, time-dependent inhibition and involvement of major drug metabolites. 

Understanding the challenges and pitfalls of drug-drug interaction studies is thus necessary in interpretation of the results of studies. In this lecture, basic methods of clinical drug-drug interaction studies will be reviewed, with examples of potential pitfalls and basic principles of interpretation.

The next EACPT biennial congress will be held in Prague Congress from 24th - 27th June 2017. The programme will provide an international scientific and educational forum for discussion of clinical pharmacology and therapeutics, including personalised pharmacotherapy. See more on our website. 

Anyone from anywhere in the world with a professional interest in clinical pharmacology and therapeutics can now join the EACPT as an Individual Associate member.

Membership benefits include
* Access to videos of talks from EACPT Meetings
* Discounted registration fees for EACPT meetings
* Online access to the Official EACPT Journal - Clinical Therapeutics
* Access to the EACPT’s worldwide network of Individual Associate Members
* Active involvement in EACPT 

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.


Incubation - an ancient Egyptian sleep cure for medical ills

The British Museum is hosting until 27 November an outstanding exhibition on underwater
From the Ebers papyrus: US NLM/NIH
archaeology from sunken ancient cities on the Nile Delta (
the lost cities of Thonis-Heracleion and Canopus).

The exhibition highlighted trade, cultural and religious exchange among old Mediterranean civilizations and in particular interchange between ancient Greece and ancient Egypt.  Examples  were featured of a major Hellenised Egyptian deities.
A fascinating element of the exhibition was discussion of a Temple for Incubation as a way to cure ills, the granite building long submerged in soft sands, its disappearance accelerated with the sands became liquid due to seismic activity. It is intriguing to note the siting of an important temple for incubation on the Nile delta, as the name for ancient Egypt was Kemet (‘km.t’) after black earth of the Nile Delta.
The aim of sleeping the night in the temple was to allow incubi - bad dreams - to carry away toxic humours as causes of illness and so heal the sufferers - in return for generous donations.
This practice reflected widespread tradition linking dreams to temples, and the release of dreams as a way to cure disease: the ancient culture of visits to oracular shrines (oracles) where a god could be consulted through an inspired priest – the most famous perhaps the Oracle at Delphi in Western mainland Greece. A common further method to consult a god was incubation: the inquirer would sleep in the temple holy place and be rewarded with an answer in a dream. This would then be interpreted by the priest with an often ambiguous answer.
Cures might also be delivered through a dream: for example at the oracle to Amphiaraus at Oropus in Attica, the temple to the god of medicine Asclepius at Epidaurus, the oracle of Dionysus at Amphicleia, and the oracle of Trophonius in Levadhia.
Ancient Egyptian medicine is considered to date at least to the 27th century B.C.E. to the time when the Old Kingdom physician and architect Imhotep was the Vizier of Djoser. Imhotep was later deified. A key belief was that disease could be caused by an angry god or an evil spirit. However the Egyptians of the time were pragmatic in formulated effective treatments.
Sources for ancient Egyptian scientific medical practices include the Papyrus on surgical trauma bought by Edwin Smith in 1862 and dating to ~1600 B.C.E and credited to the much earlier Imhotep; and the Papyrus dating to 1500 B.C bought by Georg Ebers in 1873 at Luxor. The latter papyrus includes more than 700 remedies and spells to be used to ward off disease-causing spirits.The ancient texts also describe dreams and how to interpret them.
Priests played a key role in prescription of how to live as a way to avoid disease.  There were healing sanctuaries affiliated to temples where physician-priests could prescribe for the healthy and treat patients.
Purification included special diets, ritualized bathing and removal of all body hair. The patient could also be required to maintain a specific diet including what were considered to be unclear fish and animals. Perhaps via or influencing Hippocratic sources, diet might include involving fava beans (now recognized now as a precipitate for anaemia in people deficient in the enzyme glucose-6-phosphate dehydrogenase, a genetic disorder common in the Eastern Mediterranean and in Sub-Saharan Africa).

Tuesday, 30 August 2016

Register for Updates on Cancer and Lifestyle on 29th September in London



Medical charity the FPM is organising a one-day meeting on Updates on Cancer on 29th September at the Royal Society of Medicine, 1 Wimpole Street, London. 

Register online

Abstract submission online

Consultant Oncologist Professor Robert Thomas will discuss the evidence on benefits of lifestyle and nutrition after cancer, at a one-day meeting on Updates on Cancer on 29th September at the Royal Society of Medicine, 1 Wimpole Street, London organised by the FPM.

He said: “With 1:3 getting cancer and 3 million people living with the consequences of this disease at any one time in the UK, and the cost of care increasing, the case for developing effective, self-help initiatives has never been stronger.”

His talk “summarises the international evidence, which shows that physical activity, nutrition and other lifestyle strategies can substantially reduce the risk of relapse and minimise numerous late effects ranging from fatigue, weight gain, anxiety, hot flushes, arthralgia.”

He added that his talk will “highlight the biological processes that take place in the body after a healthy lifestyle, which can have direct and indirect anti-cancer effects. By looking only at the scientific evidence, it breaks down the myths behind which foods to avoid and which to eat more of. It discusses the risks the benefits, of mineral and vitamin supplements and highlights the potential benefits of boosting the anti-cancer polyphenols in our diet. It summarises the results of the world’s largest double blind randomised study of a polyphenol rich food supplement Pomi-T, developed and tested with the help of the UK government’s National Cancer Research Network (NCRN).”

Professor Robert Thomas is a Consultant Oncologist at Bedford and Addenbrooke’s Hospitals, a Professor of applied biology and exercise science Coventry University, a senior clinical tutor at Cambridge University. He is editor of the lifestyle and cancer website (Cancernet.co.uk) and designed the 1st UK approved qualification in cancer rehabilitation. He wrote the evidence review for the UK’s National Cancer Survivorship Initiative, chairs the Macmillan Cancer Support Exercise advisory committee and directs an dynamic research unit, which has designed numerous studies which been published across the world. For these, and other, efforts to improve the long term wellbeing of patients he was awarded the British Oncology Association Oncologist of the Year, the Hospital Doctor Magazine UK Doctor of the Year and the Royal College, Frank Ellis Medal.

Southampton researcher Dr Lisa Loughney will discuss the benefits of exercise for people undergoing cancer treatment. 


Neoadjuvant treatment is treatment given as a first step to shrink a tumor before the main treatment e.g. surgery or radiotherapy.

In her 2016 paper on this theme she noted that neoadjuvant cancer treatment decreases physical fitness and low levels of physical fitness are associated with poor surgical outcome. She added that exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity that may contribute to improving physical fitness. She has therefore evaluated the evidence in support of exercise training in people with cancer undergoing the “dual hit” of neoadjuvant cancer treatment and surgery.

Dr Loughney works in the National Institute of Health Research’s Respiratory Biomedical Research Unit at the University Hospital of Southampton’s  NHS Foundation Trust.

Wendy French will discuss her Poet-in-Residency year at the UCLH MacMillan Cancer Centre.

Working with patients, sharing in their hopes and fears, tracking the everyday endeavours of a vital medical hub, Wendy French found herself drawn into lives in which blood tests, diagnosis, chemotherapy and hope become as much part of the human experience as cappuccino and Vivaldi on the radio.

Her residency resulted in publication of ‘Thinks itself a Hawk’. In the collection, one life, that of Zipora, a Jewish woman whose origins lay in the darkest days of the twentieth century, is chosen for particular attention for its power to place everyday experience in large frames, but also for the brightness with which it reminds us that everyday life is unique and important.

Wendy French was Poet in Residence at the Macmillan Centre UCLH from April 2014-2015. Her collaboration with Jane Kirwan resulted in the book Born in the NHS, published in 2013. She won the inaugural 2010 Hippocrates Poetry and Medicine prize for the NHS section in 2010 and was awarded the Hippocrates NHS second prize in 2011. She has two chapbooks and two further collections of poetry published, Splintering the Dark (2005), and surely you know this (2009). She previously worked twenty years with children and adults with mental health problems and was head of the Maudsley and Bethlem Hospital School. She has also worked with people with aphasia/dysphasia, helping them to recover their use of language through poetry.

This one day symposium will include further sessions on:
  • risk factors for cancer
  • evidence for effective strategies aimed at preventing cancer
  • medical humanities to support patients undergoing treatment for cancer

Thursday, 7 July 2016

3rd annual charity concert evening for children’s cancer charity CLIC Sargent

The distinguished University of Warwick Chamber Choir are to perform Spiritual and Shakespeare Song Cycles and A Child of our Time on Wednesday 20th July, 2016 at the Packington Estate in North Warwickshire in support of the children’s cancer charity CLIC Sargent.

Order tickets for concert and reception

Contact the organisers

This is the third in an annual series of charity musical evenings organised by the Worsted Weavers Guild of Coventry in support of this national charity, which supports children and their families in the Coventry and Warwickshire area.

The musical performance will be in the St James’ Church on the Packington Estate in
Warwickshire (~ 20 minutes north of Kenilworth).

The performance will be followed by a reception in the Pompeiian Room at Packington Hall, with wine/soft drinks and canapés. TIckets for the concert and the reception are £35 per person.

St James’ Church and Packington Hall are not normally open to the public. The neo-classical St James’ Church was inspired by the Baths of Diocletian in Rome and has an organ designed by Handel for his librettist, who was a cousin of the Earl of Aylesbury of the time, owner of the church and the Packington Estate.


Programme
Leigh arr. Woods: Don’t It Make My Brown Eyes Blue
Trad. arr. Erb: Shenandoah
Tallis: If Ye Love Me
Mantyjarvi: Shakespeare Songs
Morley: It Was A Lover And His Lass
Bennett: Weep O Mine Eyes
Passereau: Il est bel et bon
Bruckner: Locus Iste
Tippett: Spirituals from A Child of Our Time
Shearing arr. Carter: Lullaby of Birdland
Porter arr. Blackwell: Let’s Do It

Map of Packington Hall
The children’s cancer charity CLIC Sargent is the UK’s leading cancer charity for children and young people, and their families. CLIC Sargent provides clinical, practical, financial and emotional support to help them cope with cancer and get the most out of life. CLIC Sargent aims to help the whole family deal with the impact of cancer and its treatment. CLIC Sargent is active nationally, and locally in the Warwickshire and Coventry area.


Weavers church
St James’ Church, Packington Estate
The University of Warwick Chamber Choir performs in Warwickshire and further afield, with annual tour destinations including Spain, Germany, the Republic of Ireland, Belgium and Switzerland, as well as regular performances in London. UWCC have appeared on BBC national television in the Sainsbury’s Choir of the Year competition, live television in Greece, and on Central Television with Caliche with whom a CD of Ariel Ramirez’ Latin American Misa Criolla and Navidad Nuestra was recorded (the British première recording). UWCC’s wide ranging repertoire spans sacred, secular and folk music. The UWCC have premiered works by Howard Skempton and Michael Nyman and have commissioned new works from Joe Cutler and Jonathan Dove for 2015/16.

UWCCThe choir’s conductor Lucy Griffiths is the Assistant Director of Music at the University of Warwick. She studied for her undergraduate degree in Music at the University of Bristol, where she first discovered her passion for conducting. She went on to work as a lecturer in Music at Portsmouth University before being awarded the prestigious sinfonia ViVA conducting scholarship. This allowed her to complete her masters in conducting at Birmingham Conservatoire, where she was twice awarded the Sir Michael Beech conducting prize.

Sunday, 29 May 2016

Traumspiel - Martinů's French surrealism-inspired Juliette premiered by Staatsoper in Berlin

The Berlin Staatsoper have just premiered a new production of Julietta on Saturday May 28th, 2016.
Schillertheater - Berlin

The performance was held at the Schillertheater, the Staatsoper's temporary home while its main house is being renovated.

Daniel Barenboim conducted, Claus Guth directed, Magdalena Kožená sang Juliette and Rolando Villazón was on stage throughout singing, acting and miming as Michel, the forelorn Parisian bookseller.

This dream play appears inspired by Martinů's exposure to French surrealism while he was in exile in Paris. Overt themes include the fickleness of memory and desire for forgetfulness.  References to violence, loss of memory and wish for forgetfulness are especially poignant in the light of the date and place of the first performance: 16th March 1938 at the National Theatre in Prague.

At the start, Michel is seen as a source of hope of memory regained for other characters in his dream. Later Michel appears to wish to seek refuge in the world of dreams both to capture his ideal woman - Juliette - and to escape from a violent crime he may have committed.

Juliette as temptress through her songs provides a further theme, alluding to Homer, Odysseus and the Sirens, and to the old German Lorelei water spirit myth. 

The dreamworld is also portrayed as a source of fear of a vaguely recalled transgression from within the dream itself or from the real world.

How good was it? The orchestra brilliant under Barenboim's baton. The leads were outstanding, especially Magdalena Kožená for her voice and Rolando Villazón for both voice and stamina. His prolonged indecision at the end of the third Act lost him a few audience members - would he return to real life or hide in his dreams? The brass and percussion struggled with the unremitting cascade from the smoke machine into the pit – making it difficult for them to see the conductor, though not obvious from the playing.

A fine touch, at the end of multiple lively curtain calls, the entire pit orchestra on stage with Daniel Barenboim.

For the music, plot and action - you should judge for yourself if you have the chance to go.

Saturday, 28 May 2016

Berlin: encouraging the healthy lifestyle - from exercise to wildlife

In Berlin for the 5th Forum on Companion Diagnostics, organised by the rapidly expanding Brandenburg-Berlin DiagnostikNet of biotech companies and affiliates.

The event has been hosted in the CoLaborator startup building on the former Schering, now Bayer campus. Outside, a volleyball court and all weather table-tennis tables - and a giant chessboard for those wishing to divert the mind.

In the city centre, tremendous buzz around the Brandenburg Gate with an international field
Kestrel with prey in the Tempelhofer Garten in Berlin
of runners, part of the international city move to encourage exercise through amateur runs. The latest field numbers I could find were 25,500 in Berlin for a recent Spring half-Marathon.


In the South of Berlin, an inspiring example of local democracy, Berlin citizens having voted to preserve the former Tempelhof airfield as a vast wild urban common land - the former site of the Berlin Airlift (or air bridge as locally known - Die Luftbrücke: 1948-1949).

This huge space is well worth enjoying while still protected wild city green land.
 
When I visited, the runways were in use by cyclists of all speeds, stylish rollerbladers, families with pushchairs, and general strollers.

There are numerous copses and tall grasslands rich in birdlife. Within 100 yards of the entrance, a kestrel catching an unlucky field rodent (above the old parachute drop training wires), sparrows nesting in an abandoned cargo plane, pied wagtail, goldfinch, wood warbler, swifts and skylarks, common nightingale, chiffchaff ...

Many good examples of making it as easy as possible at work and in leisure time to
Common Redstart in Berlin's Tiergarten
maintain a healthy active lifestyle. This is not only of course a key part of general wellbeing, but well-established to prevent serious diseases. Cardiovascular disease is the most obvious example. 

Healthy lifestyle is also well-evidenced as good for preventing cancers, and for providing clinical benefit in patients with cancer,  the focus of a one day Updates on Cancer Meeting being organised by the Fellowship of Postgraduate Medicine in London on Thursday 29th September, 2016.

Friday, 27 May 2016

Donizetti in Berlin: playful operatic approach to placebo and quacks

Donizetti's 1832 opera 'L'Elisir d'Amore' is a multi-level satire on reverence for quacks and their
placebos, gullibility of rural communities [set in France, to spare hostility from Donizetti's native Italian audience] and the transformative effect of wealth on desire. In an engaging production [Der Liebestrank],

Berlin's Deutsche Oper makes the most of humour and farce in the opera, cheerful choruses belying the critical content of the libretto.

Berlin-based American soprano Heidi Stober is a fine Adina - the heroine of the story.

Italian tenor Enea Scala as Nemorino is almost undone in his wooing of Adina by the intoxicating effects of an Elixir bought from travelling quack Dolcamara. Nemorino expects the potion to make him irrestible to women - it is in fact wine, rather than the magical potion ascribed by Dolcamara [a showman's performance by Seth Carico] to a recipe from Tristan's Isolde - queen of the Irish. Dolcamara's non-singing assistant at times steals the show with his magician stage-effects.

The quack (from the medieval quacksalver - hawker of salves) came to prominence from the 17th century, with surprisingly not until 1881 the first organisation formed (in the Netherlands) aimed at protecting the public from quacks.    

Donizetti was inspired by the plot of Tristan and Isolde. This idea in fiction of the effective magic potion dates from ancient mythology e.g. Circe bewitching Odysseus' men and through to Oberon's 'love-in-idleness' in Shakespeare's Midsummer Night's Dream - a different kind of magic, with origins in the Roman Cupid and the viola.

To her credit, Adina rescues Nemorino from his rival, recruiting officer Becorino [Simon Pauly], and she is not deterred by erratic alcohol/placebo induced dalliances of her man [excellent Elbenita Kajtazi as Giannetta leading the inheritance-inspired female interest in newly wealthy Nemorino].

Adina eventually rescues and accepts Nemorino, not realising and therefore not influenced the fact that he has progressed from no prospects to wealthy heir during the action of the opera. The chorus is large and at best excellent, though esp. in the first act often struggling to keep up with the orchestra and to fine unposed ways to occupy the stage. 

The word placebo appears not to have been used in a health context until the late 18th Century, not long before the 1832 premiere of Donizetti's opera. However the concept of the triad of properties of a potion – medicine, poison and magic charm – dates to Ancient Greek meanings of the word φάρμακον ‎(phármakon), as used for example in Homer's Odyssey. Nemorino suffers both the perceived magical effects and actual toxic effects of his alcoholic treatment. 

As an aside, Chaucer in his Canterbury Tales, uses Placebo as name and code for the behaviour of a character in The Merchant's Tale: pleasing by flattery to obtain advantage, an interesting parallel to the behaviour of the Dolcamara in the opera. 

In medical use, although provision of a placebo may be  well-intentioned within 'do no harm' as a precept, double-blind trials in the modern era show that a placebo may have powerful unintended adverse effects.