The Mitochondria is the Powerhouse of the Cell.

According to several headlines the house of commons has today voted to allow three parents to collude in sharing their DNA to create an unnatural and experimental GM baby. The embryos created under the new mitochondrial donation law will indeed technically contain DNA of three parents, but the term is unhelpful and misleading in the extreme.

"The biggest problem is that this has been described as three-parent IVF. In fact it is 2.001-parent IVF," 

Dr Gillian Lockwood, reproductive ethicist

As anyone who did Biology at school knows, the mitochondria are vital bits of cell equipment that use oxygen to generate chemical energy from glucose. They are descendants of ancient bacteria-like cells that were engulfed very early on in life’s evolution. They each retain a tiny genome consisting of a handful of genes that are essential for the fundamental process of respiration.

Mitochondrial DNA	Nuclear DNA
Approx. 16,600 base pairs  Approx. 37 genes All from Mother Needed to produce energy for cells to function.	Approx. 3,300,000,000 base pairs  Approx. 25,000 genes 46 chromosomes – 23 each from Mother and Father. Codes for all other processes. Determines appearance and characteristics.

Mitochondrial DNA mutates more quickly than nuclear DNA as it isn't subject to the same proof-reading mechanisms. In common with nuclear DNA, small changes in the sequence can cause dysfunction and disease, such as Leigh’s disease. Babies born with Leigh’s (which causes profound physiological disruption including diarrhoea, vomiting, developmental delay, and failure of the muscles, eyes, heart and lungs) survive for only a few years. A human egg cell contains about 10,000 mitochondria, of which any number may be faulty any other children the mother of an affected baby has may well suffer with the disease too. Replacing these faulty mitochondria with working ones is a bit like replacing a faulty heart, or transfusing blood.

http://gentle-interventions.org/what_are_mitochondrial_diseases.htm

MPs have backed the mitochondrial donation regulations by 382 votes to 128 - a majority of 254.

If passed through the House of Lords, doctors will be able to apply for a license from the human fertilisation and embryology authority that allows them to implant a patient’s healthynuclear DNA into a cell that contains healthy mitochondria, thereby eliminating the transmission of disease caused by mitochondrial DNA errors, and preventing its transmission to all subsequent generations too. 

This law allows the UK to continue advancing medical science and has the potential to reduce disease burden and improve the lives of many people.

There is still quite a lot of opposition to this for some reason. Some people, including the pro-life groups, believe that human life begins at conception. A harder position to defend, or articulate, is that using this technology to eliminate mitochondrial disease is “playing God” and that this is a bad thing (and presumably using medical technology to fight cancer and infections and organ failure isn’t playing God and is fine). Still others (such as cartoon Tory Jacob Rees-Mogg) argue that we take a step onto a slippery slope that ends in parents dictating more and more details about their children until they are selecting them out of a catalogue. To be clear mitochondrial DNA doesn’t code for any characteristic of a person, and in any case the HFEA already have clear rules about only excluding embryos with clear genetic disorders (over 250 on their list) that would significantly adversely affect their lives.

As far as I can there is no significant difference in any of these arguments from those that were used to oppose “test-tube” babies born using IVF, where several embryos are created and healthy embryos are selected to be implanted into the mother. There are legitimate concerns as to whether IVF or mitochondrial donation is necessary when adoption and egg donation is available, and it remains controversial whether this type of treatment should be available on the NHS.  However, IVF technology has been shown to be very effective and quite acceptable to most people too. I see no reason why mitochondrial donation is different.

Judging the SJT

It has come to my attention that I am coming to the end of my last proper Christmas vacation. Friends and relatives are keen to remind me that next year, all being well, I probably won’t have two straight weeks off to binge on crisps and mince pies because I might have a job and responsibilities and other such nonsense. I take this realisation with great sadness as the student sloth has been my annual routine and identity for the last 24 years. But in order for this seismic transition from scrounger to “professional” to occur later this year (Happy New Year by the way), I need to first sit and pass the notorious SJT. This is the Situational Judgement Test, a confusing but essential hurdle to clear to be allocated a job.I wrote a bit about it here a few months ago when I summarised the application process and complained about having to apply for a job.

My exam is next Friday and so I figured it's about time to find out what the fuss is about. I soon realised that I was unable to adequately explain the SJT to various people that asked me, and this was a bit alarming since it is the main measure that decides whether I get to be a doctor in the NHS in August or not, and if so where.

What are SJTs and Why are they used? – according to the medical schools council. 

"Situational judgement tests are increasingly popular recruitment tools, a measurement method to assess judgement in work-relevant situations. They present challenging situations likely to be encountered at work, focusing on non-academic/professional attributes (e.g. integrity, empathy, resilience, teamwork)"

Questions go through a long process of piloting and amendment and are reviewed by psychologists and clinicians. Predictive validity for junior doctors has not been shown yet – the study will track the progress of the 2013 cohort.

SJTs are cost-effective methods to administer and score applicants compared to interviews, and are arguably fairer than essay-based application forms that can be filled out by candidate’s relatives, for example.An SJT has been used to select candidates for GP specialist training since 2007, and here they have been shown to be superior to both knowledge tests and high fidelity selection centres.

I don't really know what the arrows are for either

SJTs are also used in the FBI selection process.

The SJT also allows the system to find candidates that have severely deficient personal or professional attitudes; I will be embarrassed if I get revealed as a psychopath or a moron through taking this test. It is important to recognise the importance of practical intelligence in addition to academic intelligence in being a useful doctor. Book smarts are in books, and even morons and psychopaths can buy books and pass exams.

The SJT Practice Paper*

So I found the official practice paper online and spent a morning reading about it and then doing the test. Sitting the practice test kindled some strong emotions in me (frustration only) and I considered writing a tedious blow by blow account of my mood and thoughts. Mercifully I decided against this. So I’ll just make some sweeping statements about the questions in general to make excuses as to why I do so badly in it next week. I realise that my time will certainly have been better spent practising questions or reading GMC guidelines but I’ve started writing this now so oh well.

The test consists of 70 questions to be completed in 140mins. If my calculations are correct that’s about 2 minutes per question. My first thought was how unpleasantly the SJT scenarios portray working life. It seems that every other day I can expect to be undermined by various colleagues, or be bullied or shouted at. I also need to deal with the dangerous F1s, the infection spreading nurse, the fraudulent doctor, the shouting consultants, the drunk F1, the rude nurse, the various weeping junior doctors and the angry locum. Seven separate questions involve dealing with other F1s who refuses to do their job properly and dump extra work on me.

 The first 47 questions (about two thirds, about 94 minutes, using maths) consist of a paragraph describing a one ranks five statements in order of how appropriate they are for a given scenario. Each question is marked out of 20. Full marks are awarded if you get the order exactly “correct”, and marks are gained for getting it nearly right. For example you only lose two points if two adjacent options are switched. I think these questions are more subjective than the remaining 23 questions (choose three best options). 

The scoring system for the rank 5 in order questions

It seems to me that because the exam format is already quite artificial, the questions can never be completely unambiguous or completely fair. For some questions the order matters a great deal more than for others i.e. you could lose six marks when you risk patients dying on one question and lose six marks for finishing late on the next.

On the front of exam you can find the words “you may sometimes feel you would like more information before answering, but please answer each question based on the information provided”. Indeed in almost every single question I want more information. Without more information a candidate need to fill in the gaps sometimes, and so will be penalised if they do not make the same assumptions as the examiner. I need to correctly guess that a patients “breathing difficulty” is not an emergency and is best seen by a nurse, guess that the “Urdu speaking doctor” exists and is nearby and is free to help out when I could use his services, guess that my fictional F1 colleague would value the support of another when talking to a senior about his work-life balance, rather than find this embarrassing, patronising or an invasion of privacy. Usually guessing wrong will not have a large effect on the mark but it is still unfair that for some questions this will arbitrarily reduce the mark for some candidates.

For example one of the question calls for a candidate to choose to attend theatre for personal learning and experience ahead of checking a colleague’s prescriptions when a nurse has raised concerns about them because “Ensuring that the nurse’s concerns about errors are addressed is very important, but not immediate". I think this would be inappropriate if there were concerns that these errors endangered patients (100mg potassium cyanide PO STAT), but this important information is absent from both the question and mark scheme so one is supposed to err on the other side to caution and must assume that patient safety is not compromised to score 20/20.

Other questions do not clearly discern by what measure an option is deemed best: is it the gold standard time-consuming or expensive option that is most likely to result in a satisfactory outcome or the option that is easiest and quickest to do first? Is it the option that will definitively solve a problem long term or the option that will contribute most to patient care in the short term? For example there is a question asking what a junior doctor should do in the unlikely event that there is not enough work or training opportunities in his or her post. I think prompt discussion with the consultant and programme director is important to allow time to rectify this before the next rotation. The mark scheme suggests that one should first assist on other wards (and so this option comes before talking to the programme director), to me this is clearly what should occur to fill free time after the problem has been raised with seniors.

Some of the questions use the stem: “Rank in order the extent to which you agree with the following statements in this situation”. Honesty is apparently a desirable quality in junior doctors and I feel aggrieved that this question may require me to lie about how much I agree to get the best mark.

In over half of the practice paper questions I think it is possible to make a sensible and defendable case for an order other than that given in the mark-scheme. I therefore think it is false to have a definite single best order. In the practice paper there is usually a good option and a terrible option but sometimes options are equally good or bad. One shouldn’t lose marks if they rank the two terrible options (is it more wrong to stab the kitten or the puppy?) in the bottom slots but in an apparently incorrect order. In these cases it doesn’t make sense to order them if either order is arguably consistent with the ambiguities of the question and known best practice guidance (stab both simultaneously).

So finally to my conclusion: It is perhaps impossible to create a completely clear, cost-effective, perfect system for assessing 7000 candidates and suitably assigning them positions. It is important to show the importance of professional “soft” skills – in having an SJT test at all forces medical students to think about difficult situations and read the best practice guidance online. However, there is not enough precision in the SJT to use it to fairly stratify candidates with sufficient resolution to allocate jobs nationally.

*By all accounts the practice paper bears little to no resemblance to the actual SJT test so please continue to ignore everything I have said

Alcohol

I spent the whole of last weekend at a long and tiring pre-hospital trauma course. The medicine was relatively basic as we were mostly taught what simple life-saving procedures to do if we were to find an emergency as a passer-by, and there’s not much complicated stuff one can do without any medical kit. The main lesson for me was to avoid trauma in the first place, the presentations were crammed with excruciatingly graphic images and tragic stories. If victims of traumatic road accidents survive, and they often do with prompt emergency service attention and transfer to hospital, they are likely to be left with life-changing disability including brain injuries, paralysis, or amputations. Alcohol is commonly implicated in serious road accidents. It is a chemical close to my heart, so I decided to spend some time organising my thoughts on drinking and driving, and hypocritically lecture against alcohol use.

A tragic result from driving the morning after

In my experience, it seems that medical students as a group drink more alcohol than the average person. I briefly tried to find some data to back up or refute this stereotype but I didn’t find any numbers. Perhaps students are unlikely to admit actual alcohol consumption for articles or studies, or perhaps this information is not interesting enough to be gathered and published. This assumed culture of drinking at medical school might set the scene for unhealthy alcohol usage after qualifying; the old joke goes, the definition of an alcoholic is the patient who drinks more than his doctor. This is unfortunately seen in the levels of addiction and liver disease seen in doctors when compared with the general population. 

Now some fair disclosures before I begin preaching. I am a medical student and (therefore?) I enjoy a drink from time to time. I have drunk irresponsibly and excessively on occasions and have suffered some apocalyptic hangovers that are oddly still insufficient to condition me to stop drinking. Sometimes I drive after a pint, and worse, it seems likely that I have driven whilst over the limit in my youth – ignorantly having driven the morning after the night before. I should also make it clear that my fondness for alcohol is sometimes opposed by a personal dislike for road traffic accidents. It is a dilemma faced by all drinkers who also drive.

As of this morning (5th December 2014) the drink-drive limit in Scotland has become stricter, the maximum permissible alcohol level in the blood is now 50mg/100ml, down from 80, which remains the limit for the rest of the UK (the highest level in Europe, joint with Malta) . 50mg/100ml is a blood alcohol level of 0.05% and is the same as most European countries.  The intention is to reduce the number of drink-driving related deaths (over 200/year in the UK), not to mention the huge numbers of injured but surviving people, psychological harms and healthcare costs – particularly at this boozy festive time of year. A blood alcohol level between 0.05 and 0.08% is associated with a six-fold increase in the likelihood of dying in a car crash compared with 0.00% (and this doesn’t even take into account the harms to pedestrians unlucky enough to get struck by drink-drivers).

Graph from wikipedia

The blood alcohol numbers, while clearly stated and scientific-sounding, are nonetheless not very helpful in deciding how much one can drink before legally driving, which is what people actually care about.  Frustratingly, there are no clear guidelines on what is legal because individuals metabolise alcohol at varying rates, and the blood alcohol level will also depend on your: weight, age, build, gender, type of drink, time since drinking, amount drank, whether you’ve eaten recently and current stress levels.  Apparently, and according to popular belief, all of this taken together means that usually a man can legally drive after one pint of beer (2 units = 20ml or 16g pure alcohol) , and women can drink about half that. This should usually be ok under the stricter Scottish rules too.

Since the legal amount is so vague and variable in real terms (i.e. number of drinks) the advice is always the same:  avoid drinking if driving and avoid driving if drinking. It is too risky to guess what is legal and in any case it is safest to avoid alcohol completely. Which leads to an obvious and unpopular conclusion, why have a legal limit at all? Shouldn’t the law be consistent with the advice that no level of alcohol is acceptable? Driving with a blood alcohol between 0.02 and 0.05% is still associated with a 3x higher risk of dying.

Reaction speeds are undoubtedly slowed by alcohol consumption. It is sometimes argued that for some drivers the reduction in reaction speed from a pint, or two, will still result in “normal/legal” reaction speeds, i.e. possibly as fast or faster than distracted drivers, elderly drivers, over-tired drivers (junior doctor car insurance premiums are higher due to increased accidents following night shifts). This might well be true but misses the point that any impairment in driving ability is bad for all road users, especially avoidable impairment such as alcohol use.

The alcohol and pub lobby often claim that country pubs will suffer if people cannot drive to them or if people cannot have a drink with a meal. In my opinion if a pub is far enough away to warrant driving than it’s probably not worth making the effort to have one pint there anyway. Walking, taxis, and designated drivers seem like pretty reasonable solutions. It is also argued that lowering the legal limit criminalises the group of responsible people that drank alcohol the night before and have not completely cleared it by the time they drive. This situation is already the case, and I think its important that people are made to consider how long it takes alcohol to be metabolised (approximately one unit/hour). Further, the effect of alcohol on safe driving may be exacerbated by tiredness following a late night.

So I stand alongside nearly 80% of the Scottish population in supporting the reduction in the legal limit and would welcome the change being followed in England and Wales too. I haven’t done all of the research but at the moment I see some benefits of it being reduced further, say to 20mg/100ml.  As a medical student I am broadly opposed to unnecessary deaths, and there’s loads of evidence that control of alcohol use in drivers reduces death.

http://www.nice.org.uk/media/default/About/what-we-do/NICE-guidance/NICE-guidelines/Public-health-guidelines/Additional-publications/Blood-alcohol-content-effectiveness-review.pdf

Stoic Week

Today, Monday 24^th November 2014, is the first day of Stoic Week – an annual event started by the Stoicism Today team at the University of Exeter. The team at Exeter are some academics, philosophers and psychotherapists who run a blog that offers resources to explain Stoic philosophy and show how it can be useful in people’s lives.

I’ve taken a casual interest in philosophy since my school days, through until now this has been limited to a few popular philosophy books and internet comics, like this one. 

Superficially at least, I’ve always admired the Stoics, maybe because they feature early on in most popular histories of philosophy so I actually get to their chapter before giving up on the book. My understanding of stoicism is mostly limited to the word as it is commonly used; a stoic person is noble and uncomplaining, carrying themselves with a dignified and stereotypically British stiff-upper lip “mustn’t grumble” attitude. This ideal is basically the opposite of my usual snivelling, moaning personality and so I am quite keen to find out more about Stoicism and how it might improve my attitude to life.

To shoehorn some relevance to medicine in here, participants in last year’s stoic course reported a 14% increase in life satisfaction and a decrease in negative emotion. Like mindfulness and cognitive behavioural therapy (which are proven to be effective in treating depression), it seems likely that courses in Stoic resilience might have similar benefits in improving mental health.

Stoic Week is an event that invites people all over the world to spend a week thinking about the basic ideas of stoicism, on each day there is a different theme and some exercises to practise. The impact of stoic thinking on attitudes, behaviours and wellbeing is also assessed using online wellbeing surveys taken before and after the week. The website has loads of information about stoicism in general and includes a downloadable copy of the stoic week handbook and information on how to take part in the week.

So I signed up to the course at www.modernstoicism.com. After completing 4 brief questionnaires designed to reveal my levels of contentment (or otherwise) I was given a quick summary of Stoicism from Epictetus’ handbook. I’ll try and summarise the summary as I understand it here:

Stoicism is an ancient school of philosophy founded in Athens about 301BC, by Zeno of Citium. Other important Stoics include Epictetus, Marcus Aurelius and Seneca. The core view of stoicism is that the highest authority is reason, and Nature, life and death exist as they appear to. Nature is governed by rational principles that we cannot change nor should desire to. In contrast, emotional responses are not subject to reason; they are falsehoods. So we can control our judgements through rational thought use this to inform our actions, and our voluntary actions are the only important thing; they are our true self.

Our body, health, possessions or status are often not due to our voluntary actions, we have no control and so it is not rational to be distressed with these things. By remembering this a person can meets hardship and even their own mortality with dignified acceptance; harm cannot reach one’s true self.

A much better summary can be found on the Exeter blog: http://blogs.exeter.ac.uk/stoicismtoday/what-is-stoicism/

The first day of the course suggests spending time thinking about the level of control a person has over there situation. Stoics think that confusion between what you can control (your thoughts and actions) with what you can’t (everything else) leads to unhappiness. Broadly speaking this is good advice; I try not to get annoyed when I get caught in traffic on the way to placement or when the teaching session I drove in for is inevitably cancelled. And the reverse is true too, it doesn’t make sense to feel too smug when things go well; the fact that I don’t have any real concerns regarding my shelter, health, safety, finances, education or future are not due to my thoughts or actions, they are lucky by-products of the accident of my birth.

But overall I’m not entirely sure I can get completely on board with the stoic thinking. There're far too many unwell, unhappy, or dying people in hospitals, and most of them do indeed meet their challenges with dignity and grace. I don’t see how a person with a terminal illness (and there are plenty of them) can choose to be not pissed off even if they have no control over their situation. I guess they are supposed to realign their thoughts with their reality, and accept their fate without emotion, but this seems to me a heartless and impossible expectation. Good stoics would argue that virtue is all that is needed for happiness but I think that an absence of terrible circumstance is important too. Maybe I've not fully understood the stoic attitude here, I suppose it is only day one.

Ebola and homeopathy

A few months ago I wrote a fairly patronising summary of the ebola situation as was, and optimistically opined that perhaps the problem had been exaggerated by the media. Annoyingly, the disease has yet to burn itself out and the most current data from the WHO reports that there have now been at least 13,700 cases and 4,900 deaths.

In the UK there has been only one, imported, case of ebola. This was William Pooley, who contracted the disease in Sierra Leone and was transferred to London in August. He was treated with the new drug ZMapp, made a full recovery and has returned to Sierra Leone to continue his help.

The vast majority of cases remain in the West African countries Guinea, Liberia and Sierra Leone, and so it remains quite unlikely that infected people from these areas will reach the UK and transmit the virus here. The risk is certainly not zero however, and so Britain is currently continuing with preparations for this possibility. Most trusts have published protocols and guidance for dealing with suspected ebola cases.

Spotted in a Birmingham Hospital's ITU

I attended a lecture at my hospital on the subject, and learnt about the procedures to reduce the risk of infection, such as extra PPE and keeping such patients isolated in negative pressure rooms. Importantly, the staff were warned not to transfer suspected blood samples to the lab via the pneumatic tube system we would usually use, in case the blood vials were to break and effectively aerosol the blood and virus all around the hospital.

Ebola not welcome: A sign on the entrance to an Edgbaston GP Practice

Perhaps the most important intervention will be the use of homeopathy to combat the epidemic. Resources should clearly be diverted to the development and distribution of a homeopathic cure, you can help by signing a petition to urge the WHO to do just this. Sign it HERE*.

The good news is that a team of homeopaths have been mobilised to frontline West Africa to begin this important work.

A cynical person might suggest that sending homeopaths to ebola zones is evidence of natural selection at work. This is a cruel joke, and meaningless too because evolution doesn't exist.

Some homeopathic pills to treat Malaria

Anyway, you can already easily buy homeopathic treatment for most diseases online, including pills for dengue, meningitis and tuberculosis.

And of course mercifully there are several homeopathic clinics in Africa many of which offer cures for HIV and AIDS. Not sure if I've mentioned on this blog but I went to Tanzania earlier this year. I’ve seen a little of how devastating HIV can be to communities and individuals, but luckily charities exist that aim to help reduce this suffering. This is one of them, http://www.homeopathyforhealthinafrica.org/ and it has characteristically virtuous aims:

- To relieve the suffering of HIV/AIDS patients using classical homoeopathy
- To identify the homoeopathic remedies most successful in treating HIV/AIDS
- To spread this knowledge throughout Tanzania and Africa
- To produce formal, ethical research
- To prove to the world what homoeopathy can do

For the unenlightened, homeopathy involves taking an ingredient that causes harm and diluting it significantly, thereby releasing its healing power. The standard dilution (such as for the linked cures for dengue and meningitis above) is “30C”, meaning the original drop has been diluted by 1 drop in 100, 30 times. So 30C means one part in 1060.
This level of dilution, such that there are zero molecules of ingredient left in the treatment, is vital for the homeopathy to work.

Regrettably however, the benefits of homeopathy are denied by some groups – for example educated people and "scientists". For example, some of these “scientists” published a paper in the Lancet that compared 110 studies of homeopathy with 110 conventional medicine studies and concluded that the effects of homeopathic interventions are merely placebo effects. (1)

The 2009 official WHO statement is similarly closed minded:

“There is no place for homeopathy in treating serious illness such as HIV, TB, malaria and infant diarrhoea in developing countries.”

Quite clearly a needlessly obstructive and unhelpfully negative attitude.

In all seriousness I wish the homeopathy team in Africa the very best and sincerely hope that they manage to avoid infection,  and especially so to prevent the spread of the disease further.



*Please do not sign this stupid petition


The reference for the paper I mentioned is:
1. Shang A, Huwiler-Müntener K, NarteyL, Jüni P, Dörig S, Sterne JA, et al. Are the clinical effects of homoeopathyplacebo effects? Comparative study of placebo-controlled trials of homoeopathyand allopathy. Lancet. 2005;366(9487):726-32.