Seeing is not necessarily believing

Cartoon RatI had a post half-written, and then life got in the way (as it does). Then this happened…

The Independent and the Telegraph (among others) report that a giant rat has been found near a children’s playground in Hackney. The article has a picture of the monster rodent being held up by the chap who found it. The Telegraph speculates that this might be a cane rat – which apparently do grow to huge size – and that they might be breeding in London’s sewers. [Scream!]

And then, the Guardian also reports on the giant rat, which, it seems, is not as giant as all that. It’s all to do with your perspective, according to the chap the Guardian journalists spoke to. The Guardian article also features a “giant orange fox”, photographed in their very own offices, in case of doubt. Basically, if you hold out an object such as a rat (to take an example totally not at random) in front of you on a stick and get your mate to take a photo from the right angle, it looks as though the common-or-garden rat you’ve got is actually a huge monster rat.

As the Guardian (rather smugly) says, this is why you shouldn’t believe everything you read on the internet.

Journalistic standards have obviously sunk; one expects this kind of thing from red-top tabloids, but not from the Independent and the Telegraph (as far as I can tell, The Times has preserved a dignified – or lucky – silence). One might speculate that the growth of web 2.0, and the ability of everyone and his brother to stick news up on the internet has meant that real journalists have to make sure they get their news in quick while it’s still news, and before they get scooped by some bloke on Facebook. More expert people than I have written about this problem – journalists, even from ‘reputable’ news sources, leap on a rumour and report it as fact, or with minor hedging-words like ‘reportedly’ or ‘claiming’ – and thus people are deceived.

And that’s being charitable, and putting the misinformation down to carelessness, and not self-interest and malice. The overall standard of reporting on certain hot-button topics like immigration, Europe and human rights can’t be put down to just journalistic ignorance. If it was ignorance, surely there ought to be a few reasonably intelligent journalists out there who would learn from prior mistakes and get better at it. But reporting standards have been awful for years, so it must be on purpose. Adam Wagner, a human rights barrister, got so fed up with the poor standard of human rights reporting by journalists that he founded Rightsinfo, which exists to give people the real facts. With pretty graphics.

I find it depressing, personally. Journalists are very keen to jump up and down about their journalistic privileges being infringed – but they seem to forget that their privileges as regards information gathering and dissemination are in exchange for being the source of information the public relies on. If they are not doing their job properly by giving us reliable information, why should they have privileges?

Of course, I might be wrong. The Independent and the Telegraph might have it right: after all, Sherlock Holmes knew about this stuff. The Giant Rats of Sumatra are obviously alive and well and living in Hackney…

Multilingualism in the dispensary

In 2014, there was an incident – which seems to have been blown out of all proportion by the media – in which the dispensing of a prescription written in Welsh was delayed because the pharmacist, evidently not a Welsh-speaker, could not understand it.

Language is not specified as a requirement for a valid prescription, but as a pharmacist, one should never, ever, dispense or check a prescription that one does not fully understand. It’s a pharmacist’s duty to protect the patient by making sure that the prescription is correct – which one can’t do if one can’t understand it. A pharmacist is also held legally responsible for their part in making sure that what the patient gets is the right thing (and that’s the right thing clinically, not just whatever the prescriber ordered), so dispensing without understanding is a bad idea on all fronts.

The Royal Pharmaceutical Society therefore advises that pharmacists either use translation services, or “informal networks” – presumably the latter means the technician who speaks Welsh. Development of a “Welsh Toolkit” with useful phrases for healthcare has been suggested, but as far as I can tell, this hasn’t happened yet.

Of course, if you encounter Welsh prescriptions, presumably your patients also speak Welsh. Being able to speak even a few words of Welsh is probably a good idea – even if your language skills are limited to bore da and diolch. Most people appreciate it when someone attempts to speak their language – even if they’re bad at it. It’s not even about communicating useful information: it’s about being polite. If you live or work in Wales, especially in an area where there are a lot of Welsh speakers, learning some of the language is a way to show that your patients matter to you enough for you to make that extra effort to speak their language, instead of expecting them to speak yours. If you do acquire enough of a language to be useful, rather than simply polite, that’s even better.

Fortunately for the English-speaker in Wales who wishes to learn some basic Welsh, there is now a free internet-based course. Duolingo has just released its Welsh for English Speakers course in beta. Anyone can register for a free Duolingo account and start learning. I shouldn’t think they have the translation for “Your prescription is completely illegible in any language” or “Your doctor has prescribed a medicine that was discontinued in 1972” but by the end of it, you’ll have learned enough Welsh to make a good stab at it.

Of course, since we’re a multicultural, multilingual society, Welsh isn’t the only non-English language a healthcare professional might find it useful to learn: there are nearly as many Polish-speakers in the UK as there are Welsh-speakers. Fortunately, Duolingo has a Polish for English-Speakers course too.

New Year, sucralose and an Apple Watch

CakeSo, now we have started 2016. I distinctly remember thinking that in the year 2000, I would be really old.


I’ve had a lazy summer and autumn (at least as regards physical exercise), and now it’s time to reverse the trend of gradually putting on weight. I’ve also caved in and bought myself an Apple Watch (second hand). I got it a couple of days ago, and so far, it’s pretty good fun. It’s also nice not to have to dig my phone out of my pocket every time I want to stop or start music, knock things off my to-do list, or set a timer. It’s also going to be a better activity tracker than the iPhone – especially since my work clothes have no pockets so I end up leaving my phone on my desk at work whenever I go to the loo.  I have to admit, the challenge of getting the little coloured activity circles to close is a spur to keep moving – which is, of course, pretty much the point.

Another development this month is that I’ve started to use Splenda (sucralose) for cooking, after coming across it at work (see Rubinstein E. et al, Comparison of 2 delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr. 2014 Sep;59(3):317-20). My husband and I tend to have chocolate-chip muffins for lunch, made with a Madeira cake recipe. Obviously, that’s pretty calorie-intense, and since one really good way of burning off calories is running up and down the Hill That Shall Not Be Described in the local park, I’m quite motivated to not consume the calories in the first place.

My first idea was to swap the chocolate chips for currants. After all, they look the same…

The second idea was to reduce the amount of sugar by a third – which, surprisingly, doesn’t seem to affect the taste much as long as you put in a good slug of vanilla essence.

Idea number 3 was to use Splenda to replace some more of the sugar, and the change wasn’t noticeable.

So the recipe for Madeira cake muffins is now:

  • 175g margarine
  • 60g golden caster sugar
  • 5g Splenda (sucralose)
  • 3 eggs
  • A slug of vanilla essence
  • 200g self-raising flour
  • 50g ground almonds
  • 100g currants

Mix it all up in the usual way for cake mix, put into muffin cases and bake at Gas Mark 3 (150 degrees C) for about an hour.

Next week’s bake, I’ll see if I can reduce the sugar content even further…

It’s official. My Facebook feed is being filled by idiots.

This article :

Pennycook G et al. On the reception and detection of pseudo-profound bullshitJudgment and Decision Making, Vol. 10, No. 6, November 2015, pp. 549–563.

Read, mark, learn, and inwardly digest.

It explains a lot about Facebook.

I don’t know about anybody else, but my Facebook feed tends to sprout irritating memes and “motivational quotes”. Personally, the only thing they motivate me to do is go and find who posted it and beat them to death.

This particular type of meme-thingy tends to fall into two categories:

  1. The “uplifting” type, which basically says that the universe owes you success, so if you just wish hard enough, the universe will deliver – complete with a picture of a woman on a beach; and
  2. The “self-pitying” type, which implies that you, the reader, are the only really sensitive, wonderful, loving person in the world, and everyone else is a selfish bastard who doesn’t care and doesn’t deserve your time and attention. This type usually comes with a picture of a minion.

I found myself wondering why people post this dross, and why other people pass it on – it’s like some form communicable disease of the Facebook wall. “Hmmm… I see you have a florid outbreak of pseudoprofundity. You’d better log out for at least a week until it dies down.”

This article explains why: it’s not a communicable disease – it’s congenital.

And here’s a real profound quote:

“If you trust in yourself. . .and believe in your dreams. . .and follow your star. . . you’ll still get beaten by people who spent their time working hard and learning things and weren’t so lazy.”

By the late, great, Terry Pratchett.

Thank you, Digital Cinema Media


Digital Cinema Media, which manages advertising for Odeon, has refused to show an advertisement which was basically Christian proselytising, as people may find it offensive. The Archbishop of Canterbury, who features in it, says (as quoted in The Times) that its “about as offensive as a carol service on Christmas Day… I think people need to watch the film and come to their own conclusions as to whether it is offensive or upsetting.”

Thus demonstrating that the Archbishop of Canterbury has completely missed the point. What’s offensive is subjecting people who’ve paid good money to go and see Star Wars to religious proselytising. I don’t go to my local church and stand up at the front and say “OK guys, before you do all the god stuff, I’d just like to tell you a bit about atheism.” I respect religious people’s right to be religious on their own time and in their own chosen place. Religious people should do the same and respect my right not to have their beliefs shoved down my throat when all I want is a good lightsabre fight and some cool spaceships.

People do not need to watch an advertisement for a prayer website telling them how to pray, and then decide whether or not they were offended by having their viewing pleasure interrupted. They do not need to be subjected to proselytising without their consent, when it gives them a choice between sitting through it and walking out of the cinema.

I suppose one might think I’m getting rather exercised over what is, (in my opinion!) basically, someone wanting to talk about their imaginary friend. I suppose I should smile nicely, and say “Yes, dear, whatever you say, that’s lovely.” Or just doze through the whole thing, like any other boring advert for a product that I’m slightly less interested in than a penis enlargement. But since these people use their imaginary friend to get free seats in the House of Lords, and to force people with serious diseases to live in pain and misery, I’m slightly less sympathetic to them than to less dangerous people with imaginary friends.

Not for nothing are religion and politics no-go areas at polite dinner parties (or so I hear). What the Archbishop of Canterbury fails to realise is that there is a time and there is a place for proselytising. Any time that people have paid to experience something completely different, and any place where people can’t leave without abandoning what they’ve paid for, is not it.

Of course, on the other hand, maybe I should be glad that the Archbishop of Canterbury – in this time of falling congregation numbers – clearly doesn’t feel that voluntary recruiting is cutting the mustard, and he has to ambush a captive audience. What next, I wonder? Press gangs? Will Sundays become a time of danger as roving parties of deacons patrol the streets, bashing the unwary over the head and dragging them off to Evensong? Or getting people drunk and incapable, then locking them up until they wake up in a choir stall?

The Archbishop has made a fool of himself over this – twice: once in having the advert made at all, and once in not taking his rejection with good grace. Really, is that the impression he wants to give of the Church of England? An organisation that is not only so desperate for new blood that it ambushes filmgoers, but also is a bad loser?

If I were Anglican, it would be like that moment when your friend says something utterly, utterly stupid/racist/homophobic in public, and you just don’t know where to look (it happened; we’re not friends any more).

Good thing I’m not Anglican. I’m an atheist, and I can watch the whole train wreck from a distance. With popcorn.

Crushing Circadin® MR tablets

Whether or not it’s OK to crush Circadin® MR tablets is a question that keeps coming up over and over again. This is because it’s the only licensed melatonin tablet in the UK, and it’s probably also the cheapest and easiest to for pharmacies to obtain. This is all good. The problem is that it’s not licensed in kids, and a lot of prescriptions for melatonin are for children. Furthermore, Circadin is a modified release tablet, and as we all know, crushing modified release tablets is a Bad Thing because it’s liable to release all the drug (which someone has taken a great deal of trouble to make release slowly) all at once.

People have died from crushed modified release tablets (though not melatonin).(1-3)

However, in the case of Circadin®, the situation is a little less lethal. Melatonin is often used in immediate-release tablets, and lots of patients don’t need the modified release properties. So it doesn’t matter so much – for those patients – if the modified-release properties are destroyed by crushing.

In fact, the manufacturer – on their Circadin® website, in the Q&A section(4) – states:

Crushing a Circadin® tablet will not damage the active ingredient (melatonin). There are no safety concerns with crushing Circadin®, however it will affect prolonged-release properties of the product. The tablet matrix maintains its prolonged-release properties as long as it is ingested as a whole. The prolonged-release properties will be maintained to some extent also if the tablet is halved or divided into 4 quarters. If it is crushed it will release melatonin similarly to an immediate release formulation. According to the SmPC the tablets should be swallowed whole in order to get the full prolonged-release properties.

The information leaflet on the very nice Medicines for Children website(5) also states:

Modified-release tablets (Circadin) should be swallowed whole unless your doctor or pharmacist has told you otherwise. Your child should not chew the tablet. Sometimes, your doctor or pharmacist may have told you to crush it – this will make it act faster, but the effect will not last as long.

However, anyone advising patients to do this should bear in mind that crushing tablets generally renders them off-licence (although Circadin use is off-licence in children anyway). The GMC has guidance regarding off-licence prescribing here.

So, in short, Circadin® tablets may be crushed if:

  • The patient cannot, or will not, swallow the tablets whole AND
  • The modified release characteristics are not required (e.g. in a patient who would otherwise be prescribed a non-modified release formulation, such as melatonin liquid.

If a patient requires a modified-release formulation, but cannot swallow Circadin® tablets whole, then cutting them in half or into quarters (preferably half rather than quarters if possible) will preserve the matrix formulation which provides the modified-release characteristics to some extent.

Health Warning

If patients (or carers) are advised to crush or divide Circadin® tablets, they should be counselled carefully to ensure that they understand that this recommendation applies only to Circadin® tablets, as it is known that causing the immediate release of all of the drug in the tablet is not harmful in this case.

This advice does not apply to other modified-release products; serious adverse effects have been reported when modified-release formulations have been crushed without first establishing the safety of doing so.


  1. ‘I will always blame myself’. BBC [Internet]. 2006 Oct 26 [cited 2015 Aug 5]; Available from:
  2. Schier JG, Howland MA, Hoffman RS, Nelson LS. Fatality from administration of labetalol and crushed extended-release nifedipine. Ann Pharmacother. 2003 Oct;37(10):1420–3.
  3. Cornish P. ‘Avoid the crush’: hazards of medication administration in patients with dysphagia or a feeding tube. CMAJ Can Med Assoc J. 2005 Mar 29;172(7):871–2.
  4. Q&A | Circadin® [Internet]. [cited 2015 Nov 13]. Available from:
  5. Melatonin for sleep disorders | Medicines for Children [Internet]. [cited 2015 Nov 13]. Available from:

Patent vs Product Licence


A patent is a set of exclusive rights granted for a specific period by a state to an inventor of a product or a process, in exchange for the inventor publicly disclosing a detailed description of the invention. A patent is therefore a form of intellectual property.

The most important right a patent gives the holder is the right to control who makes, or uses, the invention. So the person (or company) who holds the patent can either use the invention themselves, or give permission for others to use it.(1)

If another person uses the invention without permission, the patent-holder can sue them to:

  • Stop them doing it.
  • Get damages for lost profits.

Product Licences (Marketing Authorisation)

Product licences (now known as marketing authorisations) are for medicines.

A marketing authorisation is required in order to put a medicine on the market.(2) The product licence is obtained from the relevant licensing authority (either the Medicines and Healthcare Products Regulatory Agency [MHRA], for the UK, or the European Medicines Agency [EMA], for the European Union), upon production of satisfactory evidence of efficacy and safety.

A medicine cannot be marketed without a marketing authorised, and where a licensed (authorised) product exists, prescribers should prescribe that product unless it is unsuitable for a particular patient.(2,3)

The Difference

  • A patent protects an invention. It allows the inventor to prevent others using his invention without his permission.
  • A product licence (marketing authorisation) protects patients. It ensures that only medicines which have met certain standards of evidence with regards to safety and efficacy are allowed to be put on the market.

If a person has a patent over a drug, then he can prevent others from manufacturing it, but he cannot market it as a medicine himself unless he has a product licence.


  1. Patents Act 1977. Available from:
  2. Human Medicines Regulations 2012 No. 1916. Available from:
  3. Prescribing guidance: Prescribing unlicensed medicines. Available from:

Amorolfine, nail varnish, and the solvent solution

FingernailsOne of the treatments for fungal nail infections is amorolfine nail lacquer. It’s medicated, but as far as I know it’s not a pretty colour. There’s also a bit in the instructions about not using nail varnish while you’re using amorolfine. The question I got asked (by a man) was, why should this be so?

If he’d been a woman, he’d probably have known the answer. Not because men are inherently stupid, or because women are inherently good at organic chemistry, but because more women wear nail varnish than men. I hardly ever wear it myself, but I still have a couple of bottles which are lasting quite well, considering I don’t remember when I bought them.

But the thing that you know, if you’ve used nail varnish more than once or twice, is that a new layer of nail varnish can dissolve an older layer. It’s useful if you’re caught short without any nail varnish remover, but not so good if you’re trying to repair chips or make really great designs.

The reason it works is because of the solvent: most nail varnishes use ethyl or butyl acetate as the solvent. This evaporates when the nail varnish dries, leaving a hard layer. If, however, you add more solvent (as in, more nail varnish), then the original layer will be dissolved again and you can wipe it off.

And when it comes to amorolfine, it’s just nail varnish with an antifungal in it instead of pretty colours – and it uses the same solvents as ordinary nail varnish. So if you put ordinary nail varnish on over the top of your medicated antifungal nail varnish, you risk your antifungal nail lacquer either coming off or getting diluted. And if that happens, there’s the risk that it won’t work as well. So, it’s safer all round just to have boring nails until the infection is gone.

The end is nigh? Homeopathy on the NHS in Glasgow

Fairy Gold

Fairy Gold

A judicial review challenge to Glasgow Health Authority’s decision to stop funding referrals to a homeopathic clinic has failed. You can read the judgement here.

This is a considerable relief to those of us who support evidence based medicine – that is, who believe that the NHS should spend its limited resources on treatments that have good evidence that they actually work, or at least probably work.

I’ve been the person trawling through the research papers, trying to figure out whether a particular treatment is beneficial or not. I’ve written the final report for the formulary committee, so that they can decide whether the evidence is good enough, or not, to commit patients’ health, and NHS money, to. It’s therefore a continual astonishment to me that “alternative” treatments seem to get a free pass.

There is no good evidence that homeopathy works. Any non-alternative treatment that had as little going for it as homeopathy would have been ditched years ago. Yes, I can understand that homeopathy was popular in the 19th century, when it actually was a good option. When the alternative is medicines containing mercury or arsenic, then little sugar pills start to look really good. I’d pick the sugar pill over the mercury chloride myself. But modern medicine has moved on.

Nowadays, we’ve got beyond the stage of “Just don’t kill the patient, eh?” Nowadays, we actually aim to make people better, and a lot of time we even achieve it. And, since the NHS is paid for by the taxpayer, we also try to do it in a cost-efficient manner.

Why is it that “alternative” treatments get held to a lower standard than mainstream medicine? Why is it that all you have to do is tell some kind of mystical cock-and-bull story, and suddenly you don’t have to jump through all the hoops that the boring old scientists do?

But what really gets my goat about homeopathy is that it is based on a fundamental error. The chap who started all this – a Dr Hahnemann – noticed that preparations of cinchona bark cured malaria. He further noted that taking cinchona bark induced malaria-like symptoms in himself. He therefore came up with the theory – not unnaturally, given the state of medicine at the time – that a thing that induced symptoms in large quantities would cure them in small quantities. Thus homeopathy.

Unfortunately for Hahnemann, and the theory of homeopathy, the reason cinchona bark cures malaria is because it contains quinine. Which is still one of the main drugs for treating malaria. Cinchona bark cures malaria not because of any homeopathic principles but because it’s chock-full of a powerful drug that kills the malaria parasite.

So, despite the fact that the entire theory of homeopathy is based on a massive (though understandable at the time) error, it’s still surviving. I wonder if it’s because most people want to believe in the magic, the fairy-dust? Maybe the people holding the budget want to believe in little sugar pills because, compared to monoclonal antibodies, they’re cheap. If we could all just take a little sugar pill and get better, or if the fairy tale about the gold at the end of the rainbow were real, the NHS would not have the financial woes that it does.

But the NHS does not waste time searching for fairy gold, and it should not waste money on homeopathy. This judgement represents one more step taken in the fight against waste and inefficiency.

Good work, NHS Lothian.

Fun with statistics: Low numerators

statistics-706382_640Last week, I came across a great statistical trick that I had to rush out and share with everyone, because it was so incredibly cool.

It’s about ratios with low numerators.

The problem you have with interpreting clinical trial results sometimes is that sometimes the event you are looking for either didn’t happen, or only happened once or twice. This means that it would seem to be quite difficult to calculate a reliable risk for that event – particularly if it didn’t happen at all.

Luckily, help is at hand, and there is a simple statistical method to obtain an upper 95% confidence limit for a zero numerator (when the event doesn’t happen at all), or 95% confidence intervals for when you have a numerator between 1 and 4 (i.e., the event happened between 1 and 4 times).

This enables you to judge how reliable your study results are – or, at least, what’s the worst that could happen.

Numerator is zero

For example,

“We reviewed 14,455 eye examinations done with the drug fluorescein, and nobody died.”(1) Surely, a death rate of 0/14,455 means that either nobody ever dies after a fluorescein eye examination – or, alternatively, that the risk of death is uncalculatable?

Well, the former is difficult to believe, and the latter is unacceptable. So does this mean that in order to calculate a risk of death, you have to keep doing whatever it is, until somebody dies?

Well, we could probably make some estimates about the maximum risk.

Obviously, we are not going to be able to calculate an accurate chance-of-death if nobody has died yet. However, if 14,455 patients in a row had the examination and they all survived, then the risk can’t be too high – for instance, it couldn’t be 1/100, or even 1/1000, because probably we wouldn’t be so lucky as to get all the way to 14,455 without somebody dying if that was the case. On the other hand, we couldn’t be quite so confident about saying that the risk of dying must be less than 1/10,000 – because our first death might just be a bit late. We certainly couldn’t say that the risk must be less than 1/15,000. So we know there must be an upper limit where we can say “we’re pretty sure that the chance of dying isn’t any more than X”.

So, if we can work it out like that, there must be a proper way of doing it. Fortunately, Hanley and Lippman-Hand(2) come to our rescue.

In medicine, we tend to deal with 95% confidence intervals a lot. Basically, your 95% confidence interval is where you can say “I’m 95% confident that the real result – if we checked the whole population and not just a sample – would be within this range.” (It’s a bit more complicated than that, but this is a useful way of thinking of it.)

We use 95% because it’s a convention that a 5% chance that the results of your study are completely due to chance, or otherwise unrepresentative of reality, is low enough that we can live with it. Hanley and Lippman-Hand report a simple way of finding out where the upper limit of your 95% confidence interval is (i.e., the point at which you can say “There’s only a 5% chance that the real number is beyond this point”).

All you have to do it:

Upper limit of 95% confidence interval = 3/n, where n is the number of people in your group.

So, for the fluorescein patients above, we do 3/14,455 = 1/4818. So, we can be 95% sure that the risk of death after an eye examination with fluorescein is less than 1/4818. It might be a lot less – but it probably won’t be any more than that.

And that’s a very comforting thing. Now we have some real numbers.

This is important, because there’s a very real difference between a risk of approximately 1/5000, and a risk of zero.

Low numerator

But what if we tested a lot more patients, and one died? Would our problems be over at that point?

Yannuzzi et al(3) said “We looked at 221,781 eye examinations done with the drug fluorescein, and only one patient died.” So, that gives a chance-of-death of 1:220,000. Fantastic!

However, what if the 221,782nd patient (who didn’t quite make it into the study), also died?

That would be a chance-of-death of 2:221,782, or round about 1:110,000. Twice as often. Just with one more patient. This makes those numbers seem suddenly less comforting.

But fortunately, there is a mathematical workaround for this as well.(4) The following table gives a “fudge factor” numerator to use  for different sizes of observed numerator and different sizes of denominator group.

Upper Limit of Exact 95% Confidence Intervals From the Binomial Distribution
Observed Numerator*
Denominator 0 1 2 3 4
10 2.6 4.5 5.6 6.5 7.4
20 2.8 5.0 6.3 7.6 8.7
50 2.9 5.3 6.9 8.3 9.6
100 3.0 5.4 7.0 8.5 9.9
200 3.0 5.5 7.1 8.7 10.1
500 3.0 5.5 7.2 8.7 10.2
1000 3.0 5.6 7.2 8.8 10.2
*for zero numerators, it’s a single upper confidence limit. The others are confidence intervals.

So, for a group of 221,781 patients, of whom 1 died… well, the table doesn’t quite go that far. But the “fudge factor” numerator to use for an observed numerator of 1 and a denominator of >1000 is going to be at least 5.6.

So, if we use 5.6: 5.6/221,781 = 1/39,604.

So the worst it could possibly be is a risk of death of approximately 1/40,000.

And how accurate is that?

Well, in 1983, Zografos(5) reported on 594,687 angiographies with fluorescein. In his study, he found that 12 patients had died. And that results in a risk of death of 1/49,557.

Zografos didn’t give us any confidence intervals, either, but his observed frequency of death after fluorescein angiography is very close to (and on the right side of) our estimated upper confidence interval from the smaller study by Yannuzzi.


  1. Beleña JM, Núñez M, Rodríguez M. Adverse Reactions Due to Fluorescein during Retinal Angiography. JSM Ophthalmol. 1:1004.
  2. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right?: Interpreting zero numerators. JAMA. 1983 Apr 1;249(13):1743–5.
  3. Yannuzzi LA, Rohrer KT, Tindel LJ, Sobel RS, Costanza MA, Shields W, et al. Fluorescein angiography complication survey. Ophthalmology. 1986 May;93(5):611–7.
  4. Newman TB. IF almost nothing goes wrong, is almost everything all right? interpreting small numerators. JAMA. 1995 Oct 4;274(13):1013–1013.
  5. Zografos L. [International survey on the incidence of severe or fatal complications which may occur during fluorescein angiography]. J Fr Ophtalmol. 1983;6(5):495–506.