Pernicious Anaemia Society
As I have said previously, for the past six years there have been two main objectives of the Pernicious Anaemia Society: the first was to get the way PA is diagnosed thoroughly reviewed and, though it wasn’t as thorough as some people would have wanted, the Updated Guidelines by the British Committee for Standards in Haematology that was published earlier this year goes a long way to achieving this. Now we are concentrating on the second objective which is to “allow patients a choice of replacement therapy treatment including delivery method and
frequency of delivery”.
There are, however, a number of major problems to overcome in order to achieve this objective. And the first one relates back to the new guidelines mentioned above. The Guidelines for Cobalamin and Folate Deficiency does not address the most common cause of complaint by members of the Pernicious Anaemia Society if not all patients which is that many of our members are unable to receive replacement therapy injections based on their need but are given what is probably the lowest denominator ( The most basic, least sophisticated level of taste, sensibility, or opinion among a group of people – The Free Dictionary) for treatment. The guidelines do nothing to address this problem other than referring the way in which treatment is prescribed to the British National Formulary (BNF) which publishes twice a year the handbook for doctors telling them how to treat and prescribe diseases and illnesses. The BNF states that treatment for Pernicious Anaemia is a 1mg/ml injection of Hydroxocobalamin every twelve weeks except where there is neurological involvement where the treatment is an injection every other day until there is no further improvement (the new guidelines state that it is difficult to justify allowing this treatment to go on further than three weeks and so the next edition of the BNF will probably take this into account). So, in order that patients can get treated according to their own individual requirement and by using a delivery method of their choice it is easy to see that all that is needed is for the society to contact the BNF and tell them that the current treatment method is often inadequate and causes unnecessary suffering that impacts on the patients work commitments and family life etc etc. Oh! that it would be that simple. Almost immediately it became apparent that this was not going to be an easy task. The BNF you see, is not a single enterprise but a joint publication by the British Medical Association and the Royal Society of Pharmacists – and it doesn’t stop there.
It begins with a review of developments in the past six months (the publication is updated twice a year) and that review begins with taking a look at recent developments. As the BNF website puts it “Information on drugs is drawn from the manufacturers’ product literature, medical and pharmaceutical literature, UK health departments, regulatory authorities, and professional bodies.”
And there is some cause for optimism because – “Information in BNF publications has been validated against emerging evidence, best-practice guidelines, and advice from a network of clinical experts”. I like the bit about ‘emerging evidence’ which provides a gateway for the society to provide the editors about the growing use of Methylcobalamin as replacement therapy (10% of those who completed our survey used this unlicensed form of B12).
The Editorial Team is made up of a number of Clinical Writers and each Clinical Writer is responsible for editing and updating specific chapters of the BNF and the BNF for Children (I’m just going to concentrate on the BNF for the time being though in time we will have to get involved with the Children’s edition). The Clinical Writers have to be convinced that any new information comes from a trustworthy source and is “reliable and relevant”. And so I will now assemble what evidence there is from reliable and relevant sources that some patients respond better to one form of B12 than another. The critical issue on any evidence that I might submit is that it has to be reliable and relevant which cannot be anecdotal evidence. This is going to be an issue but one that I will work on.
Any newly drafted section is then sent to the Joint Formulary Committee (JFC) and it is the JFC that decides on “matters of policy and reviews amendments to the BNF in the light of new evidence and expert advice” - my italics. So what “new evidence” do we have? Well, we have our survey results which were published earlier this year, and we also have other papers showing that some people show marked improvements in symptoms when Methylcobalamin is administered. As to the “expert advice” – well, over the years we have established relationships with a team of highly respected doctors and scientists who I’m sure will be pleased to be involved in our campaign. You may be wondering how this evidence and advice can be submitted to the BNF and I suppose it all points to a Review or Report. However, I’m still unsure which is why I have written 18 letters this week to the Presidents and Chairs of all those associated with the BNF – see below.
According to the BNF website the composition of the JFC “includes doctors appointed by the BMJ Group, pharmacists appointed by the Royal Pharmaceutical Society, and representatives from the Medicines and Healthcare products Regulatory Agency (MHRA), the UK Health Departments, and a national guideline producer”. And it is to the heads of all of these agencies and organisations that the letters mentioned above have been sent simply to get the ball rolling so to speak.
So once debated by the JFC the proposals are then sent to a team of “expert advisers” – and there are over a hundred of them made up of doctors, nurses, pharmacists and dentists. The role of these expert advisers is to:
“ensure that BNF publications remain reliable by:
- commenting on the relevance of the text in the context of best clinical practice in the UK;
- checking draft amendments for appropriate interpretation of any new evidence;
- providing expert opinion in areas of controversy or when reliable evidence is lacking;
- advising on areas where BNF publications diverge from summaries of product characteristics;
- providing independent advice on drug interactions, prescribing in hepatic impairment, renal impairment, pregnancy, breast-feeding, children, the elderly, palliative care, and the emergency treatment of poisoning.
Just how many of these advisers will be aware of the alternative B12 treatments available is not known but I take heart in the following:
“In addition to consulting with regular advisers, BNF publications call on other clinical specialists for specific developments when particular expertise is required”. So if our suggestions are taken seriously and get to this stage hopefully we will be asked to identify an expert who will be able to comment – and we do know some reliable experts who would gladly get involved.
There are other Sources of Information that feeds into the BNF as well as Expert Advisers. These include:
Summaries of Product Characteristics (SPC). These are what their name says – summaries of the characteristics of all new or revised products – or as the website puts it the BNF “receive summaries of product characteristics (SPCs) of all new products as well as revised SPCs for existing products” Now, ask yourself if you consider Methylcobalamin to be a ‘new’ or ‘revised’ product? Are nasal sprays, sub-lingual drops, skin patches ‘new’ or ‘revised’ forms of B12? And you should ask this because what the JFC people will specifically doing is “comparing the indications, cautions, contra-indications, and side-effects with similar existing drugs. Where these are different from the expected pattern, justification is sought for their inclusion or exclusion”; in other words will the Methylcobalamin compare favourably with the already prescribed hydroxocobalamin and cyanocobalamin? They will also be “identifying potential clinical problems or omissions and seeking further information from manufacturers or from expert advisers; “and constructing, with the help of expert advisers, a comment on the role of the drug in the context of similar drugs”.
As well as the Experts and SPCs other sources of information used by the BNF include:
Literature. Clinical writers monitor core medical and pharmaceutical journals.
Systematic reviews. BNF Publications has access to various databases of systematic reviews (including the Cochrane Library and various web-based resources).
Consensus guidelines. The advice in BNF publications is checked against consensus guidelines produced by expert bodies including NICE.
Reference sources. Textbooks and reference sources are used to provide background information for the review of existing text or for the construction of new text including Martindale the complete drug reference.
Statutory information. The BNF routinely processes relevant information from various Government bodies including the British Pharmacopoeia Commission, the Commission on Human Medicines (CHM) and UK Health Departments. I’ve written to the CHM and all UK Health Ministers. And we’ve got the petition on the Government’s website to raise awareness.
Pricing information from the NHS Business Services Authority.
Comments from readers. Readers of BNF publications are invited to send in comments. Numerous letters and emails are received by the BNF team. Now, I’ve never read the BNF though I have studied on or two individual pages so I’m not a “reader” but I have sent a letter in to them. And I’ve sent them two emails.
Comments from industry.
Virtual user groups made up of doctors, nurses and pharmacists
Market research. Market research is conducted at regular intervals to gather feedback on specific areas of development – and I hope they ask us!
Is all of this scrutiny necessary? Is it vital that all of these different organisations and individuals need to be involved?
Of course it is – these people sanction some pretty dangerous preparations that are quite rightly subject to such thorough investigation. Whether these same rigorous standards should be applied to a harmless vitamin is a matter for you to decide – as far as I’m concerned I’m quite pleased that these people do what they do. If I am going to inject something into me I want to know it is safe. There is no alternative to the process – there are easier alternatives but I prefer to be safe rather than sorry.
So, that is the mountain we will have to climb in order to achieve our next objective – that patients be given a choice of treatment and that treatment is based on the individual’s requirement.
Who’s up for it?
A few weeks back I wrote about a large conference on Folic Acid and B12 taking place in Steamboat Springs, Colorado, USA.
Yesterday I met with one of the British attendees for an update on the outcome of the conference.
I was expecting some positive results – the triumph of optimism over experience.
The conference was hugely successful, not for solving any of the problems with B12 and Folic Acid, but for new, previously unknown
discoveries being presented for the first time.
Central to the whole problem in determining healthy levels of B12 is the issues of analogues. Analogues are a mystery and although they are known to interfere with producing an accurate picture of the B12 status in people. Analogues ‘mimic’ or ‘impersonate’ B12. This is known. What isn’t known is really fundamental to understanding their effect on determining B12 status – nobody knows what they are.
Take Seaweed, Dulce or Tangle as it’s known (because it tangles around everything – cute eh?) is known to contain not only large amounts of iodine (it smells like some nurses) but also high levels of Vitamin B12. So, all you vegetarians out there need only eat some seaweed in some form – dried, boiled or raw- and you’ll get all the B12 you need correct? Wrong- the B12 in seaweed is an analogue of B12 and won’t do you any good.
It’s so reassuring that there are international conferences being held that are being attended by some very clever people all dedicating their working lives to trying to understand the nature of B12 (and folic acid), but it seems there is still a very long way to go before this dedicated school of scientists find the answer to the difficult questions they ask. Different people, it appears, have very different analogues of B12.
And the emerging sciences? Keep your eye on developments in Epigenomics and I’ll leave it at that.
It’s often easy to forget the difference we make in the day to day lives of members. I’ve just received this from a member who I telephoned earlier on in the week.
Just a quick thank you note to Martyn. You phoned me two days ago when I said I was on cyanocobalamin instead of hydroxocobalamin. I took your advice and visited my GPs practice. A different doctor said immediately I was on the wrong cobalamin, apologised, and said she would talk to the other doctor. She injected me there and then, and set up another series of injections.
Interestingly, she also said that the new guidelines In Scotland are for an injection every 10-12 weeks, so things are moving away from the inflexible 12 week period and in the right direction!
We’ll keep on doing what we do!
Yesterday in the Independent newspaper there was an article on how the UK’s Local Government Association have issued a warning about the dangers of using Nitrous Oxide as a party drug and calling on YouTube, Facebook and Twitter to issue warnings about the gas. YouTube in particular was singled out as having a duty issue warnings about videos that glamourise the use of the gas as a recreational drug. Facebook has a number of pages that offer supplies of the whippets that are the main ways in which the gas is obtained; I’ve just taken a look on Facebook and the people of Glasgow in particular will be pleased to know that for just around £1 a canister the gas can be delivered to your door along with ‘other supplies’ which presumably means the balloons used during the procedure. And the Facebook page ‘Nitrous Oxide Cardiff University‘ also offers a delivery service ‘EXAMS OVER??? FANCY SOME GAS?? WELL GIVE US A CALL’ there follows a mobile telephone number. Yesterday evening on the BBC’s 6o’clock news there was also a short piece on the rise in the recreational use of Nitrous Oxide.
So what is going on?
Nitrous Oxide was first discovered by Joseph Priestley – the same chap that discovered Oxygen. If inhaled it makes you laugh, often uncontrollably. It also gives a brief sense of euphoria which is why it is being used as a recreational drug.
What makes Nitrous Oxide particularly appealing to users is that it is cheap and not illegal and it is readily available in the form of ‘whippits’ or ‘whippet’ – small canisters of pressurised N2O that are used in both catering and domestic kitchens to whip cream – these are also known as ‘chargers’. Cream Whippers cost around £20 (there are hundreds for sale on eBay and Amazon) and when cream is added the cook then inserts a whippet into the machine, presses a lever and the nitrous oxide flows through the cream producing whipped cream with little or no effort. Those who use the gas for recreational purposes insert a charger and attach a balloon on the nozzle that is intended to deliver the whipped cream. Obviously no cream is inserted otherwise, well you’d end up with a balloon full of whipped cream. The lever is depressed and the pure nitrous oxide fills the balloon. The balloon’s contents are then inhaled to produce the desired effect. Once the machine is purchased the users just buy the chargers – they cost around 30p. Users can also take the easy route and simply buy ready inflated balloons which I understand are available in nightclubs and other venues that are sold at a mark up by peddlers.
Now, you may be wondering why I’m concerned that (mostly) young people are using this gas as a recreational drug. Well, there’s the problem that in rare cases it can cause oxygen deprivation and there is always the danger that the gas will also contain other dangerous gasses such as butane and pentane (a mixture that is used in various industries) which seriously increases the danger of asphyxiation. But there’s one particular reason that I am concerned that young people are increasingly using N2O – it seriously depletes the users B12 which, as we know, can sometimes take many years to be identified as the cause of the user’s symptoms. Here’s what Air Products one of the world’s biggest producers of N2O says in its Safetygram 20 information leaflet for customers:
Most, if not all, chronic effects of nitrous oxide are related to vitamin B12 inactivation by the gas. Therefore, individuals with a vitamin B12 deficiency may be more vulnerable to effects. Long-term exposure to nitrous oxide has been associated with peripheral neuropathy (disorder of the nerves typically starting in the hands and feet) and megaloblastic anemia (red blood cell disorder).
And that’s why I’m concerned – none of the increasing number of articles about the increasing use of Nitrous Oxide mentions the fact that users risk developing serious irreversible nerve damage caused by inhalation of the gas. And the use of the gas as a recreational drug is certainly growing. Last year 470,000 young people in the UK used nitrous oxide recreationally according to government statistics. In just one night last month Hackney Council in east London reported that 1,200 canisters had been seized from outside pubs and clubs in Shoreditch – the canisters being whippets. If this goes on then B12 Deficiency will become an even bigger issue than it is at the moment and some academics believe that 40%, maybe even 50% of people in the industrialised world are already deficient in B12. These figures seem set to rise even further with all of the consequences that will bring with it.
Whilst Industrial users are warned of the long term consequences of exposure to N2O it seems that those using the gas as a recreational drug are blissfully unaware of the long-term problems associated with it. That is why I wrote to the editor of the Independent yesterday to voice my concern. I wonder if they’ll print it? Well have to see.
THEY DID! Today
“Why isn’t anyone doing anything about this?”
It’s a question I get asked regularly, the premise being that nobody is doing anything about the problems associated with the diagnosis and treatment of Pernicious Anaemia, which, as we know, causes serious vitamin B12 deficiency. Every day newspaper headlines and television news carries stories about diabetes, obesity, depression and, the seemingly current ‘flavour of the month’ Dementia and how scientists are working on ways to prevent or cure these and other diseases. It is easy to come to the conclusion that nothing is being done to address the problems in diagnosing and treating Pernicious Anaemia in particular and vitamin B12 deficiency in general. It is commonly believed that since the introduction of artificial B12 injections in the early 1960s nothing is being done to understand just how important this vitamin really is. Vitamin B12 has been put to bed and nobody seems to want to wake it.
Thankfully that isn’t the case. There is a band of people from various scientific disciplines who are all too aware that there is still an awful lot to learn about B12 and folate. And it’s an international community who spend a great deal of their time and work trying to unravel the intricacies of Vitamin B12. The work involves researching, publishing and presenting papers at conferences that are regularly held to discuss all aspects of B12. One such conference ended yesterday (Friday) after a week of discussions and investigations into Tetrapyrroles (vitamin B12 is, apparently a Tetrapyrrole but I’m afraid you will have to look that one up yourself). The conference was titled ‘Tetrapyrroles, Chemistry & Biology of Hemes, Chlorophylls, Bilins, Corrins (Vitamin B12) and Related Cofactors of Life’ and was held in Rhode Island in the USA. A quick scan of the programme of papers being presented gives a remarkable insight into the nature of what was being discussed.
The week started with the introductory paper on “Catalytic Repurposing of Heme Protein Scaffolds by Exaptation of Conformational States” and from that humble beginning a whole week’s worth of papers were presented including:
“Genetically Reprogramming E. coli as a Cobalamin (Vitamin B12) Producer”
“Heme Sensing, Synthesis, and Degradation in Bacterial Pathogens”
“Chlorophyll Digestion and Function in the Insect Gut” and the worryingly sinister “The Dark Side of Heme Utilization in P. aeruginosa”
Some of the papers would appear to have crossed over from a conference on criminology – “The Enzymology of B12 Trafficking” , while others are refreshingly brief and to the point – “Vitamin B12 and Dementia” .
This conference was a gathering of some of the brightest minds in science, all concerned with the little vitamin that plays such an important part in the lives of patients who have Pernicious Anaemia.
And there’s another dedicated conference being held in the charmingly named Steamboat Springs in Colorado, USA between the 3rrd and the 8th of August this year - Folic Acid, Vitamin B12 and One-Carbon Metabolism. I don’t know what One-Carbon Metabolism is but feel free to enlighten me by leaving a comment, but I do know that there are some interesting things that are going to be discussed and many will be particularly relevant for patients with Pernicious Anaemia. Here’s a sample:
“Folic Acid Fortification: Progress and Challenges”; “Effect of Methyl donor Deficiency and Fetal Programming on the Liver of Wistar Rats”; “Developmental Exposure to Maternal Folate/Vitamin B12 Imbalance Programs Adiposity and Glucose Homeostasis in Adult Mice”; and here’s something I touched on in my first book – “Efficacy of MethylB12 and Folinic Acid Treatment in Autism”; “Factors Affecting Bioavailability of Vitamin B12” – the list goes on.
You see, there is an awful lot of activity centred around the scientific understanding of B12 and on the consequences of not only any deficiency but also on how it reacts with other chemicals or in certain situations. It is a fallacy that B12 and Folate are ignored by scientists – it just doesn’t make the headlines.
I was toying with going to the Colorado conference but I’m in the middle of writing the second edition of my first book which will be, incidentally, about three times the length of the first edition – I’ve learned so much and become aware of since the original was published. So I shall instead be doing my bit to raise awareness of the importance of the vitamin. If anyone is thinking of going along you could help me enormously by simply standing in the foyer of the conference venue and hold up a banner that asks the simple question “What Is An Analogue” – if anyone can give you a simple explanation please let me have it…….thanks.
Now here’s a story to ponder – and it’s not an isolated case. A man with Pernicious Anaemia is receiving an injection of B12 every three months (this is the ‘normal’ treatment regimen in the UK). After a month he starts experiencing the symptoms of B12 Deficiency. He gets that strange tiredness, he becomes irritable, he forgets words, his family notice the changes in his personality. He struggles on until the time has come for his injection. So, he makes an appointment to see the practice nurse, arranged to take a morning off work and dutifully turns up at the local health centre where he rolls up his left sleeve to save the nurse’s time.
It’s a Friday. He is summoned into the nurse’s room, take a seat and presents his arm to the nurse. She checks his records and shakes her head.
“You have to have the injection every three months” she says.
“Yes” he replies
“But it’s only 11 weeks and five days”
“But I can’t come on Monday as it’s a bank holiday and you are closed”
“Well you’ll have to come back on Tuesday” says the nurse as she puts the injection back in the fridge.
Think that’s unusual? It’s not, it happens all too frequently. Just like patients who are told that, because their B12 levels are now normal or high (well they would be – after all the injections are supposed to do just that) their injections will now be stopped all together. That happens so often that it is almost normal to get two or three reports every week. And then there’s the case I am dealing with at the moment – a pregnant lady whose injections have been stopped because “you have too much B12 and it will harm the baby”.
Let’s take another scenario – let’s go to the far east. We walk into a shopping centre and are greeted by advertisements for a brand of B12 injection. We go to a supermarket and choose five ampoules of B12 in the form of Methylcobalamin and take them to the checkout. The ampoules are cheap and you hand over a few coins and return home where you take a clean single-use syringe and inject the contents of the ampoule using a small needle – there’s no need to find a vein or a muscle – you just inject the B12 under your skin in the top of your thigh. And then you carry on with your life.
These two situations reveal just how disparate the treatment of Pernicious Anaemia is. And because there is such a variation in how patients’ B12 Deficiency is treated it causes unnecessary suffering (to various degrees), patient frustration and, perhaps more importantly health inequality.
Let’s try to clarify what is going on by looking at what we know and what we don’t know for sure. And I’ll start with what we don’t know.
Firstly we don’t know why some patients need more frequent replacement therapy injections than others. There are doctors who know that some of their patients need more frequent treatment than others because when their additional injections are sanctioned the patient ceases to make frequent return journeys to the doctors practice and go about their daily lives as best they can. Some doctors notice a marked improvement in their patient once treatment is prescribed according to the patient’s needs. However, and this is the tricky bit – the science behind all of this is simply not there. Nobody has fully investigated why some patients need more frequent injections than others. Instead doctors assume that because some patients manage perfectly well on an injection every three months (in the UK that is) then every patient should be able to benefit fully from an injection every twelve weeks and that this is perfectly adequate. Because the science to explain different patient needs is not there they look at the lowest denominator as being the norm rather than the other way around. Instead of taking the twelve weekly regimen as the norm they should, perhaps, think of a monthly injection as the norm and if patients can and do manage perfectly well on a three monthly treatment regime then all is well and good. The problem centres around the fact that there is simply no decent scientific data or evidence that will explain why some patients need more frequent injections than others. And here’s an interesting fact – it is often the case that it is not the patient who notices that he or she is experiencing the original symptoms of PA (irritability, mood swings, tiredness etc) but the family, friends and work colleagues of the patient who begin to notice changes in the behaviour of the patient. And this is especially true when it involves patients who are dependent on others for their care – children and those with special needs.
That isn’t to say that the whole of the medical profession is ignoring this issue. I know of several doctors who hold various hypotheses as to why different patients have different needs. Some believe it is due to molecular imperfections at cell level; or perhaps it is all due to faulty cell receptors; or maybe it’s to do with gut bacteria; or perhaps it’s to do with the way in which the patient turns the artificial B12 into the biologically active form. There are lots of theories, but sadly no hard and reliable research findings that would give a credible explanation of what is going on. And because there is this lack of scientific evidence doctors are left with only two options: either they can prescribe more frequent injections an in so doing fail to practice their art based on scientific knowledge or they make the only other option which is to assume, and it’s a big assume, that the patient is ‘imagining’ their need. I had this last week when a caller to the office told me that her doctor had told her that if he gave her more injections then she would soon return and ask for more; “the more I give you the more you will want them” the patient was told. I get this all the time.
So now let’s look at what we do know. Well, the first startling fact is that when the 1ml of 1mg/ml of Hydroxocobalamin was introduced in the UK as the B12 of choice in 1963 the British National Formulary (BNF which sets out the guidelines for treating all manner of diseases) stated that the injection was to be given every month. In 1974 that was changed to ever two months and, in Thatcher’s Britain, in 1984 it was changed to “every 12 weeks”. And I mention Margaret Thatcher for a very good reason. Every month she used to visit a doctor in Harley Street to receive a vitamin B12 injection – even though she didn’t have Pernicious Anaemia.
We also know that there is great dissatisfaction among patients with Pernicious Anaemia in the UK. Over 2/3 of respondents to the PA Society’s survey stated that they were ‘dissatisfied’ with their current treatment; and you have to remember that a great many of the 1/3 who were happy with their treatment were either being allowed more frequent injections by their doctor or were buying B12 from other sources and treating themselves with or without their doctors approval or knowledge. 10% of respondents to the survey were using Methylcobalamin as their choice of injection even though it isn’t licensed in the UK.
So what about these alternative sources of B12 Injections? Where are patients finding injectable B12 and perhaps more importantly why are they being forced into by-passing their doctors? The answer lies partly with what I have said above – that the science to explain why some patients need more frequent replacement therapy than others is not there and unfortunately the lowest treatment regimen is taken as the norm, and partly in the British Medicines Act of 1968 that states that any medical product that is delivered to the patient parenterally (via an injection) can only be obtained via a doctor;s prescription. That’s why you cannot walk into a pharmacy (or supermarket) in the UK and simply buy injectable B12.
So, patients who have Pernicious Anaemia who live in the UK and who cannot convince their doctor that they would benefit from more frequent replacement therapy injections of B12 either and experience the return of their symptoms before, sometimes long before their prescribed injection either suffer needlessly or obtain injectable B12 from other sources. And some of these sources are very dubious indeed.
I’ll start with the safest sources of injectable B12 – those prescribed by a doctor and dispensed by a pharmacist. And yes it does happen in the UK – there are GPs who are willing to depart from the guidelines for treating Pernicious Anaemia as set out in the BNF and will treat their patient according to his or her individual need. Unfortunately we in the Pernicious Anaemia Society don’t get to hear about these cases very often for a very good reason. Obviously, if a patient is receiving their replacement therapy B12 when they want it they are unlikely to seek help from a patient support group. This is the same reason why we have so few members who manage perfectly well on the three monthly regimen – they have no need for extra support and just go about their daily lives with their condition not affecting them in any way. However, we do get patients who are receiving their injections whenever they want them (usually every four or five weeks) but who contact the society because they are still experiencing their symptoms to some degree. Just why these patients should experience the symptoms of B12 deficiency when they are getting so many injections remains a mystery. I know of at least two doctors who inject themselves twice or three times a day – perhaps the patients on monthly injections need them even more frequently; what is certain is that the evidence to support this is solely anecdotal and lacks any scientific explanation. Prescribing injections to patients more frequently than the guidelines suggest does, unfortunately, have consequences for medical professionals who are investigated by the organisations responsible for overseeing quality and ‘good practice’. And this is why doctors are reluctant to prescribe more frequent injections than mentioned in the BNF.
The next safest option open to patients whose National Health Service doctors refuse to prescribe more frequent injections is to turn to the private sector. Here, the patient can pay for his or her extra B12 which is often offered in different forms, cyanocobalamin, hydroxocobalamin or the increasingly popular methylcobalamin. Some patients report responding better to one or the other various types of cobalamin though why this is so is again unexplained. Interestingly 10% of respondents to the survey used methylcobalamin which is not licensed for use in the UK. And it can be expensive – especially if the compounding pharmacy where it is made opens up its operation to third party quality assurance agencies.
The third option available to UK patients is to buy their injections from pharmacies in mainland Europe. This will usually be in the form of cyanocobalamin. The patient then injects him or herself or gets a family member or friend to inject them. In the best case scenario the person carrying out the injection will have received appropriate instruction, will use established hygiene practices and also use a lockable sharps bin. Unfortunately, best practice is not followed.
And now we get to the more worrying options of by-passing normal medical practice and sourcing B12 from what could be rather risky and potentially dangerous places.
Internet ‘Pharmacies’ have become an increasingly popular source for patients buying additional B12. The interesting point here is that individual suppliers are being championed and recommended by individuals and so in the process some are trusted more than others. The internet has shrunk the world and so it is not surprising that enterprising individuals are capitalising on the fact that many patients cannot get the treatment that they need. This sector continues to grow and now there are elements of price cutting and other promotions as the competition increases. These ‘pharmacies’ do not only supply injections of B12, they also offer various other forms of B12 including sub-lingual drops, lozenges and sprays (the B12 gets into the patient’s bloodstream via a membrane under the tongue), nasal drops, trans-dermal patches and even anal suppositories. The amazing thing about all of this is that nobody has evaluated the efficacy of these alternative treatments. The problem faced by anyone carrying out any evaluation will be how the products efficacy could be measured; they will all raise the patient’s serum B12, but will they make him or her feel better? I won’t go any further into this because it’s an enormous question that involves some highly complex biochemistry. One sub-lingual spray has been evaluated in a laboratory and shown to replenish B12 levels and is becoming increasingly popular as it’s available in high street health food stores.
Intravenous Drips of a ‘cocktail’ of vitamins including B12 are another option for patients who are not benefiting from the normal treatment regimen. This is the increasingly popular choice of ‘celebrities’ and there has been much press coverage of various people from the world of entertainment receiving these bagfuls of vitamins and minerals in various combinations. And I know that this is a popular treatment for more and more of the PA Society’s members. Alarmingly though, they are being offered by people, entrepreneurs, who are not medically qualified or trained. Even some hairdressers and beauty parlours are offering this procedure and these institutions are not subject to any regulations.
All of the above alternative sources of replacement B12 are readily available to anyone with a computer and internet connection and there is now a growing demand for their services. That demand is being enthusiastically met by health food shops and internet providers. It really is time for the whole issue of a ‘one size fits all’ treatment regimen to be thoroughly investigated. The way in which Pernicious Anaemia is currently treated is by far the single biggest cause of complaint by our members. It’s hard to get your head around the fact that in the UK patients with Pernicious Anaemia were better treated in the 1960s than they are now.
So here we are – seven years after we began the campaign to get someone who knows what they are doing to review the way in which PA is diagnosed we now have a new set of Guidelines produced by the British Committee for Standards in Haematology that acknowledges that there are serious problems with the way in which Pernicious Anaemia is diagnosed. It’s strange to reflect that during the campaigning to get the way PA is diagnosed looked at it one of the options we used to put forward to doctors was that we wished that medical professionals would go back to how they used to diagnose the disease basing their decision on the patient’s symptoms rather than on the result of a blood test. We were told that that would never happen. However, the very first Recommendation states that “the Clinical Picture is More Important than the test result” so in effect the new guidelines are retrospective in that they are now telling doctors to listen to the patient rather than concentrate solely on the test result.
It took seven years of hard work to get our concerns listened to – five years of building up a good name and presenting our evidence in a calm and rational manner but five years on those doors that we were knocking on started to open. Our paper that showed the results of our survey of over 1,300 members experiences in getting diagnosed was carefully analysed and presented using the preferred format of a respectable health journal and the results showed just how the poor diagnostic procedure currently used was effecting the everyday lives of people. So, the battle to prove that the society (and me) were not dangerous nutcases finally paid off and thankfully we are now being asked our opinion on various aspects of B12 – we were even sent a copy of the draft guidelines to comment on.
Now we have had to ask ourselves ‘where do we go next’. It wasn’t a difficult question to answer. Ever since its inception the society has identified two key areas that are badly in need of reform. The first concerned the problems with the way in which PA is diagnosed and, as we have seen from the new Guidelines, those issues have now been addressed. And so now it is time for the society (and me) to start work on the second problem we face as patients – the ridiculous way in which replacement therapy B12 is provided, not only in the UK but throughout the world. And this is where I start to outline just how big a problem this is; not only for patients but also for their families and friends.
Let’s first of all go back to the early 1920′s. If you were one of the unfortunate people to have been diagnosed as having Pernicious Anaemia the term ‘pernicious’ meaning ruinous, deadly, fatal, would tend to concentrate your attention. Despite whatever your doctor would try to help you, the prognosis was not good and you would die following a long drawn out but inevitable journey. Your family and friends would only be able to make you as comfortable as possible and would have to look on helplessly as you began your final journey. Then, in the middle of the 1920′s it was discovered by doctors in the USA that eating liver, and lots of it, could keep you alive. Liver and other offal, preferably eaten raw, would mean that you could spend the rest of your life looking forward to your next dinner and hopefully a novel way of being served your lifesaver portion (they used to liquidise liver, make liver soup and all manner of other ways of trying to add a little variety into the patient’s diet). Now this would be bad enough if you happened to like liver, especially raw, but even if you couldn’t stand the stuff it would, presumably, be better than the alternative – death. Fast forward to the second half of the 1940′s and liver extract injections became available. Highly concentrated liver could be injected directly into the patient who could then join in with the rest of humanity and look forward to a less strict diet. Now, notice that nobody was told how much liver the hapless patient had to eat. He or she would eat and ingest as much liver as he or she could bear. You see, there’s no danger of overdosing on liver, not even the greatest fans of liver have ever been told to take it easy and try to cut down on their intake. Imagine somebody telling someone who enjoyed liver to try and have it just three times a week. It didn’t happen. And no doubt, though I haven’t been able to find any evidence of this, some patients needed liver, preferably raw, more often than others. While some patients would manage to stay alive on just one or two delicious platefuls of raw liver a week, others might need it twice a day. Now, imagine if you can that you are a doctor in the 1930′s and you had one patient whose family made sure that the he or she consumed liver at least once a day. As a doctor you would presumably congratulate both the patient and the family on their enthusiasm for the only treatment available at the time which was keeping the patient alive. You may wonder at the resolve of the patient and marvel at his or her enthusiasm for all things offal but you would never suggest that he or she limits the amount of liver being eaten. There was, however, a problem although this was not known at the time. Liver is high in Vitamin A (Retinol), which had been identified as early as 1013 but was not named until 1920 and much later it was discovered that taking too much Vitamin A causes weak bones. At the time that liver was being used to treat, though not cure Pernicious Anaemia this link between too much Vitamin A and Osteoporosis was not known and patients were free to bulk up on as much liver as they could manage. In 1948 two independent teams, one in the US and one in the UK identified a new vitamin, vitamin B12.
From just after the Second World War and the late 1950′s concentrated liver injections were used to keep patients alive and then, following the discovery of the molecular structure of B12 in the mid 1950s by Dorothy Hodgkin (who was awarded the Nobel Prize in Medicine for this exceptional discovery) industrial scale production of artificial B12 began and this became available to correct the B12 Deficiency in patients with Pernicious Anaemia from the late 1950′s and early 1960′s.
The chemical composition of B12 is the most complex of all of the vitamins. and even today just what it does and what it is capable of is still a mystery to the dedicated team of expert doctors and scientists who have dedicated their lives to studying it. And now that we’ve had a brief history of the vitamin it’s now time to turn our attention to the purpose of this story – why there is an urgent need for there to be a review of how patients with Pernicious Anaemia receive this lifesaving little molecule.
Well, that was a fine first half of the year. Two incredibly important milestones were reached and they both occurred within two weeks of each other.
The Strategic Plan of the Society, that was written five years ago, stated quite clearly that there were serious problems surrounding Pernicious Anaemia. Firstly there was the problem with the way in which the disease is diagnosed. New Guidelines on diagnosing and treating PA were due to be produced in June 2012 but, following a highly successful meeting at the Department of Health in May 2012 those new guidelines were postponed and after two years the new guidelines were produced in May of this year (2014). Most importantly those new guidelines included recently published research papers that provided the evidence, the scientific evidence, that the current assay used to determine the B12 status in patients was seriously flawed. And just before the new guidelines were issued (we were shown the new guidelines in draft form which I commented on) our own research into patients’ experiences in getting diagnosed was eventually published in the British Journal of Nursing. This paper, designed and analysed by three doctors, provided statistical evidence – credible statistical evidence – of what was previously only anecdotal evidence as told over and over again on the society’s online forum. And so, these two events, the new guidelines and our own paper together have shown just how poor is the diagnostic process for determining B12 Deficiency and whether that deficiency was due to the quite specific disease called Pernicious Anaemia. It took five years for us to be acknowledged as a credible patient support group by senior figures in the world of medicine; five long years of knocking on doors and writing to newspapers and magazines before finally we secured that meeting at the department of Health in May 2012. And then it took another two years for the new guidelines to be produced. And if there’s one thing I have learned from that experience it’s that changes in medicine don’t happen overnight.
However, whilst the new guidelines acknowledge the fact that patients and doctors are being let down badly by the current test they failed to address the second problem that was highlighted by the original Strategic Plan – that there are serious problems with the way in which patients are treated. Instead of acknowledging this problem (and we made sure that this was a major subject of discussion during the May 2012 meeting) the new guidelines simply refer the matter to the British National Formulary for them to deal with. And so whilst the new guidelines dealt with, or at least acknowledged that there are serious issues with the current test to determine B12 status, the second of our problems was not dealt with at all other than acknowledging that any neurological involvement should be treated by an injection every other day (something that was already in the BNF guidelines) but added that the writing group of the guidelines couldn’t see any reason this should continue after three weeks. This is annoying because, more than anything else, it was a recommendation or suggestion that was, as far as I can determine, not based on any scientific basis – it’s more an opinion than a hard scientifically based judgement.
And so we still have the problem that the current treatment regimen in the UK for treating Pernicious Anaemia is nothing short of a farce and remains the single most common cause of complaint to the society.
Let’s take a look at events in the past week. On Wednesday (today is Friday) I received an email from a member who is in her fourth month of pregnancy. The email was not hysterical in nature but calmly enquired whether it was normal for patients who were pregnant to have their replacement therapy injection of B12 stopped “in case too much would harm the baby”. This is not the first time we have heard of this by a long shot but what struck me as odd about this request was the casual nature of the question. It was as if the writer had found the fact that her injections had been stopped a trifle odd and it had obviously been niggling her. And so she took the step of seeking assurance from the society that her doctor was in order and that she should stop worrying. We responded immediately telling her that her injections should never be stopped (as per the new guidelines) and that there was no danger of overdosing on B12 and that if anything she would need adequate levels to ensure the baby was not born deficient. She was told all this and a copy of the leaflet on Pregnancy and PA was attached. It was just another ordinary request for information from a patient whose health and that of her new baby were at serious risk of being compromised because of the confusion among some medical professionals about vitamin B12. I wonder what the atmosphere was like at her next visit to her doctor?
This was not an isolated incidence, some of the horror stories that we here in the society’s office on a daily basis make this request seem almost routine, but I mention it because it happened at the same time as another incident that proves the need for a serious overhaul of the current treatment of Pernicious Anaemia.
In the north of England there’s a GP who, for many years, has treated all manner of symptoms with regular doses of vitamin B12. He is adored by his patients, admired by his colleagues who are often truly amazed at the outcome of his treatments and he is very unpopular with his local Primary Care Trust who are deeply suspicious of his liberal prescribing of a harmless vitamin, and the Medical Practitioners Tribunal Service (part of the General Medical Council) have, through the Interim Order Panel recently renewed an order that restricts the doctor from prescribing B12 for anything other than Pernicious Anaemia. The doctor hasn’t done anyone any harm, has offended nobody and delighted thousands. And so why is the GMC taking this action? It’s simple – the scientific evidence on the benefits of B12 in treating all manner of other conditions is simply not there. Just as the society only had anecdotal evidence from the online forum that there was serious issues with the diagnosing of PA so too the doctor only has his case histories of the benefits he has brought to patients with a wide range of problems. Yes, there is some, and I mean some science as to what B12 does, and certainly the doctor is not alone in the medical profession who has discovered the incredible benefits that B12 can give to people, but that science is very small compared to other investigations carried out in laboratories. His case studies are well recorded and read like a book of miracles, but until the science is there to explain the benefits of B12 people like him will always be on the defensive.
Blossom was a cow whose hide hangs on the wall of the St George’s Medical School Library (now in Tooting south London). And you may be wondering why the hide of a dead cow should adorn the walls of a medical school library. Well, she played an important tole in the development of medicine. Edward Lister was a family doctor who had become aware of the fact that milkmaids who had caught cowpox were usually immune from the much nastier smallpox. At this time (the 1790s) it was said that 60% of the population caught smallpox and that 20% died of it. Small pox was a nasty and often deadly disease. Jenner made the connection between the immunity of milkmaids to smallpox – and following the advice of his teacher – “don’t think, act” – Jenner scraped pus from the cowpox blisters of Sarah Nelmes a milkmaid who has spent many an intimate hour with Blossom the cow. He then inoculated James Phipps, an eight year old son of his gardener in both his arms. The boy became mildly ill but did not go on to develop smallpox – he was immune. Now, why am I telling you this? Because the science behind the experiment was not known. There was no scientific hypothesis or explanation – it was just well known that milkmaids caught cowpox but didn’t go on to develop the much more serious smallpox. Jenner didn’t have the scientific background to justify the experiment, all he did was find out if the old wives’ tale that milkmaids were immune to smallpox was true – and it was. Of course, it could have all gone tragically wrong and a certain gardener could have found himself with one less mouth to feed and medicine has moved on a long way from the time when doctors could carry out such experiments that are based on no more than hearsay and a hunch and that is why doctors who use B12 so liberally are viewed at best as curiosities and at worse as quacks, but there’s a whole world of difference between injecting boys with pus from blisters and using an incredibly safe and cheap vitamin – nobody has ever reported that any treatment involving B12 has caused any harm, at least as far as I’m aware. The science isn’t there but it works and if they neglected to provide patients with this harmless vitamin then surely they could be seen as guilty of failing in their calling to ease and prevent patients’ suffering. Of course the real heroine of all this is Blossom – a bovine whose contribution to the development of Immunology is thankfully recorded on the wall of a library.
So, this week we have had a pregnant woman whose life-saving injections have been stopped and a GP being told he can’t prescribe any more B12 – there’s something sadly and badly wrong with the way vitamin B12 is provided. It’s a mess!
Tomorrow I will explain how the society is going about changing how we are treated for the better – a treatment regimen based on the needs of the individual who is offered a choice of how he or she receives that treatment.
Now that the new website is up and running and in safe hands it is time to turn our attention to our Awareness Week that will take place in October of this year.
Yesterday we applied for a grant to have a series of posters professionally designed and printed and I have written to several MP’s who are sympathetic to our cause asking them to arrange a series of events in the Palace of Westminster. These events will include the following:
Parliamentary Reception – the last one we held was six years ago and was not successful as we had statistical evidence about how poor the current diagnosis and treatment of PA is – this time we will be able to make a presentation.
Prime Minister’s Questions
Early Day Motion
Questions to the Secretary of State for Health
Hopefully, really hopefully a Westminster Hall Debate.
We will be asking all of our members to write to their MP requesting that he or she attends the reception, signs any Early Day Motion, takes part in any debates and is made aware of the problems that we face in getting an accurate and timely diagnosis with treatment based on the individual’s needs. Already there is a link on the website so that members can quickly find out who their MP is and how to contact them. We will be providing a downloadable pro-forma letter that will make the whole campaign as easy as possible.
Between now and October me and the other volunteers will be busy making all of the necessary arrangements.
More on this as it happens.
Today the new website has gone live and hopefully that event marks the end of the worst six months in the history of the society.
It was just before Christmas 2013 that the company that had looked after all aspects of the website went into administration and we were left without any paid support. It has taken six months to raise the necessary funds to make all manner of changes to the website that included changing servers, domain names and a host of other complicated stuff.
It is easy to forget just how big the website is and how much of a role it plays in patient’s lives. The new website features a special section especially designed and built for medical professionals. For the first time doctors will now be able to download a unique fact sheet that contains all of the latest developments in diagnosing and treating Pernicious Anaemia. It is fully referenced and gives details of how the current test used to determine B12 status and whether any deficiency is caused by PA is not fit for purpose and it also tells of what we as a society are doing to make others aware of this.
Sadly, the Forum has now been suspended. Two of the most knowledgeable moderators resigned earlier in the year and the sheer number of members posting questions made it impossible to moderate effectively. We now have links to Health Unlocked:
“HealthUnlocked is a social network designed for people who care about their health and the health of others. With hundreds of dedicated communities run by patient charities and health organizations and a million users visiting monthly it’s the fastest growing hub for health support and information”
So, with the website management going into freefall and the hugely popular forum being suspended the last six months have been one long headache as we searched for solutions to the problems. Hopefully the second half of 2014 will be a lot less complicated than the first six months.