Views of No Man's Land

Ian McKellen as Spooner (L), and Patrick Stewart as Hirst in No Man’s Land.

Photo: Johan Persson

On 15th December, a remarkable live broadcast of the National Theatre's production of Pinter's play. The close-ups showed fine acting business beyond the experience of all but the front rows at Wyndhams' Theatre - and the occasional well-disguised mishap.
Read no more if you plan to see the play and wish to form your own view.

A stark first half was followed by fine comic display by the cast of four, the play closing with a return to themes implied by the title of the play. The Guardian's Michael Billington notes that the "beauty of Pinter’s play is that it is open to many interpretations and concludes that No Man's Land is "both desolate and funny and conveys, without peddling any message, the never-ending contrast between the exuberance of memory and the imminence of extinction." His earlier view was that play may give insight into dark professional fears of Pinter: the successful but lonely Hirst (played by Sir Patrick Stewart) the mirror image of failed poet Spooner (played by shabbily dressed Sir Ian McKellan). It less clear whether there is any autobiographical - or biographical - relevance to wealthy Hirst's two manservants, played with alternating menace, humour and compassion by Damien Molony as Foster and Owen Teale as Briggs.

A further obvious reading is that Hirst's distress is exacerbated by just-preserved insight into advancing disintegration of his mind - this evolving dementia perhaps accelerated by intensive use of a well-stocked drinks cabinet. Worth contrasting Pinter's reading with the formal portrayal of dementia by Florian Zeller in "The Father".

As shown in this production, No Man's Land, particularly given the historical setting of the play (mid-1970s), could refer to many taboo or inaccessible areas, ranging from the unwanted realms of dementia, dying and death, and to sexual politics, from homosexuality to (at least for these characters) the inscrutable minds of women.

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.

New UK initiative from 2nd March on driving and legal or illegal drugs

2nd March 2015: 
It was previously an offence to drive whilst impaired through drink or drugs.

New regulations in England and Wales, in place from 2nd March 2015, aim to reduce risk of RTAs caused by drivers who are taking illegal drugs while driving, or legal drugs which impair their ability to drive. 

It is now an offence, as it has been for alcohol, to drive with certain drugs above a specified level in the blood. Sixteen legal (see Table below) and illegal drugs are covered by the law, including cannabis, cocaine, ecstasy and ketamine. 

There is now a zero tolerance approach to 8 drugs most associated with illegal use. There will also be a 'road safety risk based approach' to 8 prescribed drugs most associated with RTA risk. It remains the "driver’s responsibility to decide whether they consider their driving is, or they believe might be, impaired on any given occasion." (page 7)

Recreational drugs are well-established as causes of road traffic accidents (RTAs). DrinkAware lists several important reasons why alcohol leads to accidents. Alcohol

• affects judgement and reasoning
• slows down reactions
• upsets sense of balance and coordination
• impairs vision and hearing
• makes users lose concentration and feel drowsy.

DrinkAware note legal limits for alcohol in the breath as 35 microgram/100 
mL for England and Wales (80 milligram/100 ml in blood) and lower at 22 microgram/100 mL in breath for Scotland (50 milligram/100 ml in blood).

Cannabis use also increases driving risk in several ways and has, for example, been implicated in 1 in 4 RTAs in France.  Furthermore alcohol and cannabis are often used together and in combination can increase risk of a road traffic accident.

For recreational drugs, safety when driving may be impaired both during use and during drug withdrawal.  

Several commonly prescribed drugs are also expected to reduce alertness and lead to increased risk of road traffic accidents.

People who are having difficulty sleeping may already when awake have reduced ability to concentrate on key tasks, including driving. Poor quality of sleep combined with night sedation may  together reduce alertness further.

Other drugs may have sedative effects as a less obvious action – for example opiate like drugs used to treat pain.

Patients who are concerned about the effects of their prescribed drugs on their safety while driving should consult their pharmacist of medical adviser.

The Government's website notes that:
 'the new law provides a medical defence if you’re taking your medicine in accordance with instructions – either from a healthcare professional or printed in the accompanying leaflet – provided, of course, you’re not impaired.'

It also notes that:
'If you’re driving and you’re on prescription medicine, it may therefore be helpful for you to keep some evidence of this with you in case you’re stopped by the police.'

The following blood level limits for prescription drugs are noted to be:

‘Medicinal’ drugs (risk based approach)	Threshold limit in blood
amphetamine	250µg/L
clonazepam	50µg/L
diazepam	550µg/L
flunitrazepam	300µg/L
lorazepam	100µg/L
methadone	500µg/L
morphine	80µg/L
oxazepam	300µg/L
temazepam	1,000µg/L

UK Government's drug driving website

Drug Driving: Guidance for Healthcare Professionals

DrinkAware website

Methylphenidate (Ritalin) – does use by ‘healthy’ students matter?

In their report in the Telegraph, @Josiensor and Rosa Silverman discuss implications of a survey from Cambridge which notes that so-called 'smart' drugs continue to be used by students to try to improve their academic performance, with methylphenidate (Ritalin) a common choice.

Why should this be of public interest?

Methylphenidate has been in use since 1960 for treating ADHD, with effects mainly considered to be improvement in attention and concentration. It is used to treat a number of rare syndromes involving abnormalities in chemical transmission in the brain. The drug is also reported to be in widespread use by students in the UK, the US and elsewhere in the hope that it will improve studying, learning and exam performance.
 

1.    Does it work? Studies of possible effects on studying and learning are typically short-term and usually based on artificial tests – ie not usually test possible benefits of the drug what students may be trying to learn, or effects on the types of exams students may be sitting. Evidence compared to placebo of benefits or risks appears limited to studies lasting 4 weeks or less.

The evidence of benefits from methylphenidate in apparently healthy students is disappointing. For example, in a study in health young volunteers there was a reported benefit from the 1^st dose for a spatial (3D) task and for planning, but not for attention or fluency. However even these effects were not sustained: with a second dose, spatial task performance was less good; ie there was little evidence of sustained benefit on repeat use of the drug and possible evidence that performance might be worse. And one of the side effects is insomnia – fatigue could also therefore be an indirect reason why performance might be impaired by the drug. There are also reports by users that with the drug, too much focus on details may make it difficult both to complete an assessment and to consider a broad enough range of issues to give a complete answer.

2.    Is use of methylphenidate any different from using caffeine? Because of the lack of convincing evidence of benefit from methylphenidate and concerns about serious risks, methylphenidate is not approved for use in the absence of specified medical conditions – e.g. ADHD. As for other drugs, the balance between risk and benefit must be considered by prescriber and user. In the event of any benefit for studying from the drug, others not using it are put at a disadvantage. In contrast caffeine is widely available for those who chose to use it. Too much caffeine, or sensitivity to caffeine can cause troublesome symptoms, including anxiety, tremor, sleep disturbance and palpitations. 

3.    Risks of methylphenidate Potential risks may be serious and include serious cardiac and psychiatric disorders. This has lead to important restrictions by regulatory authorities such as the FDA on use of the drug, even when the drug is medically indicated. 

Withdrawal symptoms of methylphenidate can include psychosis, depression and irritability.

Risks of the drug may be greater if there are medical problems, in particular if the user has a medical history of cardiovascular or psychiatric problems. Use without clinical advice may mean that important underlying conditions are not identified, for example high blood pressure, disorders of heart rhythm, and psychiatric risk; and potential important interactions with other drugs (including other stimulants) may not be considered. For example: 

-      alcohol can delay clearance of the drug from the body, increasing risk of adverse effects; 

-      concurrent use of stimulants such as caffeine would be expected to increase risk from methylphenidate of serious disorders of heart rhythm.

4.    What about access to the drug from internet pharmacies? For the above reasons, licensed pharmacies would not supply methylphenidate in the absence of specified medical conditions. Unlicensed internet pharmacies should be avoided. The quality of medicines is not reliable, with serious risk of being supplied poorly active or counterfeit or contaminated medicines. And medical contra-indications need to be identified and discussed to minimize the risk of preventable serious adverse effects.

5.    Fairness and coercion There are also a number of ethical concerns including:

a)    the need to protect students and others from using so-called ‘smart drugs’ in response to pressure to compete, both in exams and in professional life; 

b)    being fair to other students who do not have access to the drug, or do not wish to use what may be a medically harmful pharmacological aid to improving performance in examinations or to meeting challenges at work.

See also
June 2009: Opposing opinions in the British Medical Journal from John Harris and Anjan Chatterjee

September 2011: Methylphenidate and delayed puberty
July 2012: Methylphenidate for Parkinson's disease
November 2012: Commentary in the Guardian by William Leith: Ritalin before an exam fails the test of common sense 
June 2013: Cautionary report in from Canada on methylphenidate use and learning in  ADHD

What's new on health matters from Australia?

@HealthMed Recent news concerns infection alerts, raising awareness of the risks of overweight, and ethics of using social networking to undermine efforts to combat drinking and driving.

'Grabbable gut' as clue to being overweight.

How do you engage the public in long-term interest in benefits of keeping weight in check? The recent ‘LiveLighter’ Australian anti-obesity campaign campaign, supported by the The Heart Foundation, aims to improve recognition of overweight as a personal problem. The campaign includes dramatic pictures of internal excess fat, accompanied by images of a man who does not appear realise he has a weight problem - with the reminder that if you can 'grab your gut' ie have enough spare loose abdominal flesh to grasp by the handful, there is a problem.  In other cultures, 'spare tyre', or the advice 'if you jump up and down and it bounces you're overweight' ... have similar resonance. 

Some critics have complained that the campaign further lowers self-esteem in those who already feel under psychological threat - or simply claim that these messages won't work. This overlooks the obvious - increasing failure to perceive that a given build is excessive, with overweight becoming the norm, both in developed and less developed countries.

  Key challenges are more about how to raise awareness that weight is even a problem, why that matters, and what initial and long term sustainable measures will help to keep weight in check and avoid preventable long-term cardiovascular and non-cardiovascular serious health risks.

Raising public awareness is all the more pressing with recognition, for example from recent data from the US NHANESIII study presented at the European Society of Cardiology Congress in Munich, that relative overweight [based on increased waist-hip ratio] is more important than raised weight based on body mass index, for predicting increased risk of serious heart disease and other causes of premature death.

Random roadside alcohol checks

In parallel with public health messages about the risk of drinking with any alcohol in the blood, random alcohol tests are being used in Western Australia to discourage drivers from drinking.

Several different initiatives have been used in other countries. In France, by a new 2012 law breathalyzer kits are compulsory for all cars. In Sweden and the USA, alcohol ignition interlocks have been used for drink drinking offenders, and several other countries have piloted these schemes involving a breathalyzer coupled to the ignition – if any alcohol is detected, the car’s ignition is inactivated. Elsewhere, a timed arithmetic test is used as barrier to starting the car, based on the adverse effects of alcohol on brain function of even modest alcohol intake. Rather than accepting help not to drive when potentially a danger to pedestrians and other road user, some drunk drivers have been reported to use a friend or even pay a sober contact to beat the tests.

In Australia, booze bus spotters have been posting messages on social networking sites to warn drivers of its location. Worrying not least from the question how and when drivers are accessing these messages.

Rise in ’Ross River cases’

RossRiver virus, an RNA alpha virus and member of the togaviridae family of viruses, is spread by mosquito  bites and is endemic in Australia and several South Pacific islands. The illness was first reported in 1928. The main reservoir animals appear to be kangaroos and wallabies.

The features include rash and flu-like syndrome, the acute features usually settling within 12 months, with however some of those infected by the virus reporting subsequent long-term ME like debility.

Why now provide an update on the virus? Public health reports indicate a rapid ~5-fold increase in numbers of cases of Ross River disease in Western Australia over the past 3 years from, 332 in 2009-2010 up to 1570 in 2011-2012. This rapid increase has been attributed to increased numbers of the vector - mosquitos - due to a series of La Niña events [coupling of Pacific Ocean currents with weather patterns].  This has lead to an increase in rainfall in parts of Australia, the resulting humid conditions and increase in ground-water favouring greater breeding by mosquitos. 

Romeo's 'Sick health'

@HealthMed One of Romeo's string of oxymorons [Romeo and Juliet Act 1, Scene 1: reflecting on his heart sickness for fair Rosalind], 'sick health' illustrates the challenge of preventing more conventional heart disease - with its long prodrome of apparent health masking the development of sub-clinical disease from unrecognized risk factors, which may however be reversible if identified and addressed.

Why don't more people engage? Many reasons, including fear of finding a problem if tested, difficulty accessing advice/health checks, lack of interest or knowledge of outcomes of 'treatment', lack of confidence in self-efficacy to achieve supporting or first-line life-style changes, in diet, exercise, weight, smoking cessation, alcohol intake ...

To find out more on challenges and solutions for success in behaviour change, look for sources on Theory of Planned Behaviour e.g. this referenced link from the University of Twente.

See my previous blogs on smoking and alcohol.

Stopping smoking: why and how?

Hip fracture risk and smoking

Smoking: literary warnings

Alcohol: literary warnings

Alcohol and the French paradox

Alcohol and risk: surprising early warning from F Scott Fitzgerald.

F Scott Fitzgerald

@HealthMed More early 20th Century discussion in literary fiction of risks of over-indulgent lifestyle.
F Scott Fitzgerald addresses lifestyle risk twice in his 1922 novel 'The beautiful and damned': smoking as a risk for a young woman's complexion, and later in the book, risks of alcohol.
Usher girlfriend Georgina challenges Harvard man Anthony Patch on his drinking - both for the amount and as a daily habit, predicting serious disease. She comments: 'you and your friends keep on drinking all the time. I should think you'll ruin your health'. She then adds: 'Think what you'll be at 40'.
Anthony is dismissive, replying that 'I only get really tight once a week'. He is neither concerned about weekly binges nor about the long term. For him 40 is beyond his horizon.
Apparent insight, but not for him - for Fitzgerald - take heed of what he says, not as he does.
The book is remarkably prophetic in that the author himself did not live much beyond 40, dying aged ~44 after what was considered a second heart attack, with excessive alcohol considered a major health problem,  oesophageal varices suggested as the cause of a major illness. Retrospective risk factor ascertainment is of course problematic, however it is likely that his smoking contributed to his early demise, assuming the heart attack diagnoses are correct.

Notes on why and how to stop smoking. 

Smoking warnings in literary fiction

Smoking and hip fracture risk

Ideas for losing weight

French paradox

Toll-like receptor on brain glial cells - a new target to reduce acute toxic effects of alcohol?

@HealthMed Researchers in Adelaide, Australia led by Mark Hutchinson have attracted international media interest with headlines heralding a new treatment to protect from hazards of alcohol. How close is the research to human treatment? And is there a risk this could be a drug of abuse for people over-indulging in alcohol and hoping to avoid harmful effects? My discussion below complements two radio interviews, one with a Californian station, the other with BBC Radio Ulster. To listen to the interviews, use the podcast links at the foot of this blog.

This was an experimental study looking in mice at ways to prevent some of the harmful effects of a single large dose of alcohol. The authors were following up previous research suggesting a link between alcohol and the immune system. The Toll-like Receptor 4 is a member of a family of inflammation-inducing receptors, first described in the fruit fly. TLR-4 is present on immune defence white blood cells in the circulation. TLR-4 is also present on glial cells in the brain. Glial cells make up around 90% of cells in the brain and have an important defence role against brain infection.

The scientists used two approaches to find out whether TLR-4 is involved in unwanted effects of a large single intake of alcohol: animals with genetic absence of TLR-4 and its pro-inflammatory signalling pathway partner MyD88; and the drug (+)-naloxone.  This is the mirror-image version of the (-)-naloxone in clinical use to treat an overdose of an opiate such as diamorphine (heroin) or morphine. (+)-naloxone blocks TLR-4 without blocking the enkephalin receptor through which opiates act.

Hutchinson and colleagues studied two adverse effects of alcohol overdose: sedation and unsteadiness. Their model of sedation was the time taken to regain normal posture (loss of righting reflex). Their model of unsteadiness was the mouse equivalent of keeping balance on a rolling log.

What did they find? The drug (+)-naloxone halved the duration of sedation after acute alcohol and shortened the recovery time for loss of balance.  These effects could have been due to 'off-target' effects of the naloxone, however findings were similar in animals genetically deficient in TLR-4 and MyD88 - reduction in severity and duration of sedation and unsteadiness. The authors also showed that alcohol switched on inflammatory protein production by cells from the hippocampal part of the brain; and they ruled out differences in alcohol metabolism between models.

What do these results mean for people?

Firstly, they are important in raising the question whether genetic variation in activity of TLR-4 inflammatory pathways plays a role in explaining major differences in tolerance of alcohol.

These results provide an interesting complementary mechanism for protective effects of naloxone on alcohol-toxicity to those reported by Badawy and Evans 30 years ago using different experimental methods.

Secondly, these findings suggest that targeting TLR-4 in the brain may be a new way to reverse some of the serious adverse effects of major alcohol overdose in patients attending emergency departments.

What about (+)-naloxone as the drug to use? Studies would be needed to confirm that TLR-4 is also important in alcohol-mediated toxicity in humans, and if so to understand more about the wider range of adverse effects of alcohol which may be prevented or reduced.

What about cautions? 

- This is experimental research which would need to be repeated in human subjects with TLR-4 blocking strategies which pose minimal toxic risk.

- Naloxone has to be given by injection - it is not sufficiently absorbed by mouth to be clinically active.

- Use (+)-naloxone is no exception to the rule that all drugs can have harmful effects. There is concern that risks of harmful effects from (+)- naloxone mean that is unlikely to be safe to use in general alcohol users.

-  (+)-naloxone may block some of the wanted mood-altering effects of more moderate alcohol intake. For example, it is known to affect other brain pathways e.g. blocking stimulant effects of cocaine and amphetamines. This may well lead to loss with this drug of the wanted effects of alcohol.

- The published study showed reduction in severity and duration of alcohol's effects not their prevention: if confirmed in people, general hazards of alcohol, for example when driving, would remain.

- (+)- naloxone is unlikely to prevent the 'hangover' from alcohol, which is recognized to be due to many factors, including dehydration (alcohol is a diuretic), low blood sugar, and other chemicals (congeners) present in alcoholic drinks and contributing to colour and taste.

The most interesting aspects of this study are that:

- if confirmed in further research in humans, assessment of TLR-4 variability may be developed as a test for susceptibility to alcohol;

- safe, effective TLR-4 inhibitors for use in humans could be a treatment for some of the physical effects of a severe overdose of alcohol in people presenting to hospital.

See the article

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Podcasts of radio interviews with Professor Donald Singer about research on alcohol, the immune system and new potential treatment:

Interview with Jon Bristow on San Francisco KGO Radio     12.17 PDT 29th Sep, 2011.

Interview with Seamus McKee on BBC Radio Ulster  16.15 GMT 28th Sep 2011. 

San Francisco KGO Radio
BBC Radio Ulster 

© DRJ Singer