This blog is "educational and emotional" according to Mr Dispenser.

Friday, 17 October 2014

Coldzyme: a result of real science being left out in the cold

There’s no getting away from it, folks. Its sniffle season. For the next 6 months or so, the sounds of sneezes, coughs, and millions of noses being blown will echo throughout the nation.

The common cold. We all know by now that it’s a virus. We all know that there is no cure. We also all know that, although you feel like crawling into a small dark warm cave and dying at the time, its usually much better after a few days, and it goes away of its own accord. Cold and flu remedies do nothing to actually get rid of your cold- they are there to make you feel better during it, although many of them are actually irrational combinations of products in shiny boxes with a redonkulously high price.

It is oft said that if someone did come up with a cure for the common cold, they would be millionaires. I was, therefore, surprised to read in the Chemist and Druggist that indeed, the first ever product to not only treat the symptoms but to act on the virus itself was winging its way to pharmacy shelves as we speak. Really?

The product is ColdZyme, a mouth spray that costs £8.99 for 20mls. Seems a pretty fair price to pay for a product which pretty much claims to cure the most prominent infectious disease in the western hemisphere. It seems odd, though, that instead of this marvellous scientific breakthrough being plastered all over the media and medical literature, the article announcing it is tucked away in a barely read corner of a trade journal.

What is this breakthrough, miracle product that will powerfully break down viruses? Well, an enzyme called trypsin. An enzyme that merrily and plentifully kicks about in your digestive system, breaking down proteins. An enzyme which, for the purposes of this product, is inexplicable being derived from cod (which has meant that I have had to resist the urge to refer to it as somewhat fishy.) An enzyme which should be stored at temperatures of between -20 and -80 degrees Celsius, to prevent autolysis.  Now, I’ve seen some fancy medicine packaging in my time, but never a simple mouth spray bottle that can manage such storage feats. So, if trypsin really is present in this product, then it seems fairly likely that its going to be inactive, unless the manufacturers have found a way of warping room temperature. Or you live in Winnipeg, and its winter.

Medicine vs Medical Device
The manufacturers make some really very extraordinary claims on their website, including one textbook example of special pleading. Their product, they state, isn’t a medicine. It’s a medical device, because it has no systemic effect. They then go on to helpfully tell us about the systemic effect it has:

“The medicines currently on the market only treat the various symptoms of a cold. ColdZyme treats the cause of the symptoms – the virus itself – and thus works both preventively against the common cold and shortens the duration of illness if you have already been infected.”

Right. So in the same breath, they are claiming that the product only forms a barrier, no more. But then they are also claiming that this barrier affects the ability of the virus to produce illness if you are already infected- viruses which are already through that barrier and inside your body. Come on, Enzymatica, you can’t have it both ways.

The Evidence
All these claims are backed up by evidence, right? Well, there is a tiny trial performed on only 46 people, which isn’t published anywhere. We can’t say whether or not it is a well designed trial, because we can’t see it in full, so to be honest, we pretty much have to just discount it. What we can do, however, if have a look to see if there is decent published information looking at the effect of trypsin on the cold virus. So I turned to Medline and Embase.

I did find one experiment which looked at the trypsin sensitivity of several human rhinovirus serotypes(1). And this appears to have found that viruses are only really susceptible to trypsin when there have been exposed to low pH, followed by neutralization- something which wont have happened to your common or garden cold viruses. I couldn’t find much else suggestive of a clinically significant antivirus action of trypsin.

The practicalities
This isn’t a simple, one-off- couple of sprays and away flies your cold sort of product. You have to use it every two hours, as well as after you brush your teeth and before you go to bed, and you have to continue this “until your symptoms are relieved”. That’s one hell of a regime. I have difficulty remembering to use medicines twice daily, never mind every two hours. I’ve never used this product, but I’d imagine that if it really does leave a “barrier” coating in your mouth, that’s probably pretty unpleasant. I can’t imagine many people sticking closely to these dosage instructions, and if the mechanism of action is as the manufacturer’s claim, skipping doses would cause the product to fail (if, indeed, it works in the first place)

We are also directed to “Start using ColdZyme® as soon as possible when you detect symptoms of a cold.”. Now, those of use who suffer with cold sores who have ever used aciclovir will know that this is often easier said than done- you probably haven’t got the stuff in the house, or at work, and by the time you’ve managed to get your hands on some, its already too late- your cold sore is out loud and proud, and using aciclovir will be pointless. The likelihood is that the very same thing will apply here- that by the time you’ve got symptoms, using this product will be completely pointless. And remember that the incubation period for a cold is about 2 days- so the virus will already be merrily settled into your body before you even know about it. Its therefore completely ludicrous that this product claims to be able to reduce the length of a cold simply by forming a barrier.  

I know it can be used as a cold preventative, but how many people who feel completely fine are going to remember to use the product every two hours, every day, for the entirely of the cold season?

To Summarise
So, do I think there is scientific evidence to back up the extraordinary claims being made by ColdZyme? I might do when hell freezes over. Or at least when some decent trials are published, which might take just as long.  Do I think that this product should be sold through pharmacies? Absolutely not- this isn’t, if you ask me, real medicine. This is pure pseudoscience, trying its best to fool you into buying real medicine. Do I think lots of people will buy this, use it once or twice, then leave it to languish in their bathroom cabinet? Absolutely.

Here’s the problem though: this stuff will appear on the shelves of pharmacies all over. The pharmacists wont have a clue what this stuff is, and because they are really busy and probably quite tired at the end of each day, they probably wont be able to do the sort of evidence review I have managed to squeeze into a quiet moment. So they’ll get asked about it, and they’ll sell it. Some people will buy it and will feel better after a few days, and will think that the spray has made them better, forgetting that colds are self-limiting anyway, and would probably have gone away that quickly regardless of the spray, not because of it. A customer might come back in the pharmacy one day, and say something like “hey, that new-fangled spray got rid of my cold!”, and the pharmacy staff will end up making recommendations on the basis of customer feedback and anecdotes, rather than on the basis of rational, scientific evidence. In my eyes, this really is a shame, and by selling this sort of nonsense, we really are cheapening our profession, and we're causing our customers to waste their money. 

If patients ask me about it, when I’m working behind the counter, I’ll tell them something along the lines of: “there’s no evidence or logical way that it works. It seems to be a bit of an expensive gimmick, with no decent basis to it. You’ll feel horrible with your cold, but it will start to go away of its own accord, I promise. In the meantime, you’d be much better off looking after yourself, having plenty of fluids and rest, and taking paracetamol according to the packet.”

Hxxx

Wednesday, 15 October 2014

A Miracle Migraine Machine?

Cefaly. No, it's not a village in Wales, nor is it a type of cheese (actually, it might be for all I know, but nevermind.) It is instead a new all singing, all dancing miracle cure for migraines, according to its manufacturers anyway. So, in our usual fashion, let's take a look at the evidence and see what on earth it is, and whether it is worth spending money on.



It's a medical headband device that you wear on your noggin, around your forehead. This means that you can easily pretend to be the Empress from the Never Ending Story. The downside is that you'll have to pay somewhere in the region of £250 to do so, plus electrodes and batteries. So, for that amount of money, you want to know that what you're getting is going to provide you with a bit more than simply cosplaying as a child-like film character.



It is essentially a TENS machine, which applies an electric current to the middle of the forehead via self adhesive electrodes. Anyone who has ever used one of those godawful Slendertone thingies on their stomach is probably right now recoiling in horror at the idea of having to endure such torture right between their eyes- I know I am. But first I suppose we need to see if it works- after all, migraines are horrible things which can massively impact on the quality of life of sufferers. Those who are desperate may be quite happy to have their foreheads electrocuted.



Its been approved by the FDA, which is nice. What isn't quite so nice is the fact that this approval is based on one trial- the one and only trial in existence, despite what the manufacturers would have you believe.



This trial included 67 patients who suffered at least 2 migraine attacks per month. Although small, this trial is well designed, with an identical sham stimulator being used as a comparison to the test product. After three months of daily 20 minute usage, the mean number of migraine days in users of Cefaly was significantly reduced (6.94vs 4.88, p=0.023), but were not significantly changed in the sham group. But here's the thing: the difference between groups was not significant (p=0.054).



There was significantly higher percentage of responders (defined as ≥ 50% reduction in no of migraine days per month) in the Cefaly group compared to the sham group (38.24% vs 12.12%, p=0.023).



There was no significant difference in severity of migraine.



Although some of the results in this trial are encouraging, it is limited by its very small size. It is worth noting that the authors and manufacturers claim that this trial proves that the product is effective at preventing migraine, despite the lack of a significant between-group difference in the primary outcome of migraine days.



Other papers have been published in the literature regarding this product, and the manufacturers try their best on their website to make them look like they are real trials. However, these range from letters, conference abstracts, experiments in healthy adults, and case studies- not robust clinical trials.



An uncontrolled survey of 2313 Cefaly rental users found that roughly just over half of patients were satisfied with the treatment and would be willing to buy the device. The rest of the patients stopped therapy- that's a pretty high number of people. There are a number of methodological and confounding problems with this study, so the conclusions drawn from it should be considered unreliable.


Being a rental user is one thing- at least they were able to try it out before taking the plunge and handing over a rather large wad of cash. In the UK, though, it seems that the rental option isn't readily available. £250 is an awful lot of money to spend on a product, especially when, for roughly half of its purchasers, its going to be used a couple of times then lie in a cupboard, forlorn and forgotten about.



Let's have a think about compliance. To get the best results, you are supposed to use it for 20 minutes per day. Now, initially that might not sound like too big a deal, but if you work, have a social life, go to the gym, or spend every waking minute building a house in Minecraft, finding 20 minutes a day for something that could be, in most cases, painful, is probably pretty unappealing, and impractical. I can't see too many people who will be able to religiously use this product exactly as intended in the long term. I'm guessing that in most cases its going to go the way of that bit of exercise equipment that you bought 5 years ago and that you've used twice and now only trip over on occasion.



So to summarise: there is a little bit of encouraging data, though it's not as compelling as the manufacturers would like us to think. It's extremely expensive, impractical, and probably pretty unpleasant to use. Its an interesting device, but one that I am placing firmly in the "Yet to be convinced by larger trials" pile.



Hxxx



Monday, 29 September 2014

Dear Kate

Thank you, Kate.

I’ve still not quite been able to come up with an adequate phrase to describe having social anxiety. Sometimes the old clichés are the best, and so I go with the duck- calmly floating above the water, but paddling like mad beneath.

I can be so good at hiding the furious paddling that even my closest friends have doubts that it exists. But if I were to invite you inside under the water, you’d see constant, frantic movement. Physiological reactions going mad for no reason, reacting to the unforeseen horror of merely having a pleasant conversation with someone. Tidal waves of thoughts rush over and over in a jumble, telling you what other people are thinking (although they are probably not), How stupid you look (although you probably don’t), how boring you are (although you’re probably not). These are all intersected by a knife of rationality, but there are so many of them it is impossible to keep up, and eventually this knife just ends up cutting you up on top of the waves, making you feel even worse in the end.

Eventually, this state becomes your norm. It becomes background noise, and the peaks of it get even higher in moments where you feel threatened. Our duck is thrashing relentlessly under the water every second of everyday, and the tiniest of waves sends him into freefall. Of course, Kate, you probably know how this feels already to a degree: it is stage fright that kept you away from us for so long.

Moments of true calm are few and far between when you reach this point, and even when they do occur, you start worrying about them- such internal silence starts to feel alien, and constant anxiety seems to be your default position. The otherworldliness of calm feels dangerous somehow.

That’s how I was this time last year. Things have now improved somewhat- thanks to the CBT, thanks to those around me, and in no small part thanks to my own stubbornness. I’m now at a point where the peaks are still there, but they’re not quite as insurmountable. My default position is no longer fight or flight, and I’m more able to ignore the thought onslaught. True moments of stillness are, however, still relatively rare.

I’m never usually able to lose myself in a moment, as this stupid anxiety makes me constantly self-aware. The other night though, I experienced several blissful hours of basically forgetting that I existed. All thanks to you, Kate.

You’ve always been able to lift me out of terrible moods. One of the joys of living on my own is that I can get home, and crank up your music as loud as I like. I can sing, I can let go, and I can dance about with the cat without anyone laughing at me. I often find that you’re able to lift me out of an approaching mist. You've been the manufacturer of one of my most reliable coping mechanisms.

I saw Before The Dawn the other night. I was scared of going in alone, but within minutes I was chatting away with other people. We couldn't believe our luck. I've honestly never seen so many utterly excited people in one place before.

I know that everyone else has loved it. I've read the reviews, and I've seen the tweets. I expected it to be good, but what I didn't expect was to be completely enraptured- with you, with the story of a woman in the water, of a dawning day, with the detail. I had expected a couple of tears, perhaps a couple of whoops if I was feeling brave. What I hadn't expected was to realise that I was so taken in by it all that I was no longer self aware. I sort of came to, whilst dancing madly away to Cloudbusting, and realised that the waves had stopped for me for 3.5 hours. Here I was, on my own, in a situation that would usually scare me, completely and utterly swept up in the world of your making.

Thank you, Kate. Thank you for that gift.


Hxxx

Friday, 29 August 2014

It's time to reclaim holism

Holistic. Its one of those words that sets a skeptic’s teeth on edge. Its basically a codename for woo, bandied about by supporters and pushers of all sorts of magic, unicorn tears, and snake oil.

But should it be? Is it time for the medical profession to reclaim the label holistic as its own, and start shouting from the rooftops about how we are holistic practitioners? I think it is, and here’s why.

holistic
həʊˈlɪstɪk,hɒ-/
adjective
Philosophy
adjective: holistic
  1. characterized by the belief that the parts of something are intimately interconnected and explicable only by reference to the whole.
o    Medicine
characterized by the treatment of the whole person, taking into account mental and social factors, rather than just the symptoms of a disease.

There is a general perception, gleefully pushed by proponents of alternative healthcare,  that somehow, conventional healthcare and holism are at odd with each other.  I don’t believe that to be true, yet the image of uncaring, white-coated medical professionals hell-bent on simply treating that one particular symptom, with no regard for the fact that a patient is attached to that symptom seems pervasive.

We don’t help ourselves, I suppose. With a limited time on GP appointments, for example, its easy to feel like you’re being rushed through the system. Some surgeries ask that you book one appointment per ailment. Our health care professionals tend to specialise in one particular type of illness, and you can start to get the impression that they only care about that particular bit of your life, despite the fact that it’s very often all interconnected. You can feel passed from pillar to post, one day an appointment with a diabetes nurse, the next day an appointment with someone else for your arthritis, and two days later an appointment with a mental health specialist. So I do understand that it can seem like, as healthcare professional, we only care about your symptoms. 
But, even at the most basic level, it is impossible, and really quite dangerous,  to really do healthcare without looking at the patient as a whole. We’re all trained to do it, and its become so second nature to us that we have all sort of forgotten to be proud of it. As a result, we’ve lost control of the word holistic and we’re allowing unscrupulous charlatans to creep in to the public’s consciousness. Of course, there are improvements to be made, but I think on the whole we do bloody well in the NHS, given the knowledge, funding and time constraints we’re lumbered with.

Now, in my day job as a medicines information pharmacist, I actually have no direct contact with patients. But I still, fundamentally, operate as a holistic practitioner. Here’s a basic example of what I mean:

GP: “Ah, hi there, I’m just wondering if there are any interactions between Champix and mycophenolate mofetil.”

In this sort of seemingly simple interaction enquiry, it is simply imperative that I look at the patient as a whole, rather than simply as two drugs out there on their own. 

If I were to look at interactions of Champix (varenicline, used to stop smoking), I wouldn’t find any interactions at all between it and mycophenolate mofetil (an immunosuppressive used in patients who have had an organ transplant). So fine, we’re good to go, right? I mean, I’ve answered the question, done my job, and all is well, yes?

No, not at all. If I’m going to safely answer this question, I need to look at the patient as a whole. I need to acknowledge that they’re not simply a smoking machine that needs to stop smoking, but they’re a living. Breathing human with a many organs, some of which may not be working, and emotions. I need to look at the patient holistically, not just as some isolated drugs.

So our patient is in his mid-forties, using the mycophenolate mofetil because he has previously had a heart transplant. He has a history of depression (understandable really, given how ill he has been in the past), and takes a couple of other medicines too (no major interactions on checking). He wants to stop smoking, which is great, a really positive step for him, but he’s failed a few attempts already whilst using nicotine replacement therapies which he’s found frustrating in the past and have triggered his depression. His liver and kidneys are working just fine.

So, looking at the patient as a whole, I need to think about how using Champix will impact him as a person.
-Stopping smoking itself might affect some drugs, as there are chemicals in cigarette smoke which can affect the enzymes that metabolise some drugs. Is this the case with any of these drugs?
-Quitting smoking itself can be a trigger for depression or suicidal ideation. There is also an association between varenicline and changes in behaviour and thinking, including depression and suicidal ideation. Given this patient’s history, this will need to be discussed with him and he’ll need to be monitored carefully.
-Certain cardiovascular events were reported more frequently with Champix than placebo in trials: we need to bear that in mind and monitor him for any adverse reactions, especially given his heart transplant
- Not giving up smoking has made him depressed in the past. Continuing to smoke increases his cardiovascular risks. A good old risk vs benefit decision needs to be made.

So I discuss all this with the Dr, and her response is:
“Oh, I didn’t think about the cardiovascular risks, thanks for that.”

By looking at the patient holistically, we’ve made sure that he will know to look out for any cardiac effects and to report it as soon as possible if he does experience any side effects. He’s also prepared for the fact that his mood might change, and knows to report any of that too. He’s willing to take these risks for the sake of stopping smoking, so we’re helping him to take a really positive step in his life, aimed with all the information he needs to do it safely.
That’s just a small example of how I practice holistic medicine in my daily life. All over the NHS, at every level, other healthcare professionals are doing the same thing in their practice. We don’t declare ourselves to be holistic, because its such second nature that we don’t even realise we’re doing it. Maybe its time to start reminding people-and ourselves- that conventional medicine does, fundamentally, mean holistic medicine. 

Hxxx