Why not teach ultrasound in medical school?

As a rheumatologist working in Northern Ireland, it is more or less expected that you should have developed some competency in performing ultrasound of the joints. Ultrasound training is now well embedded in the training programme for our Rheumatology SpRs, and this has perhaps been reflected in the very high ratings for trainee satisfaction in our region compared to the rest of the UK. Although most of us have embraced this new technology with enthusiasm and ‘gone back to school’ relearning anatomy and going on ultrasound courses, I can’t help feeling that the learning process would have been far easier had it been taught at medical school along with anatomy teaching. Using ultrasound not only challenges our in-depth knowledge of anatomy, but it can also help sharpen up our clinical examination skills. I often encourage students in clinic to examine a joint, declare exactly what they have found, and then I can test their findings using ultrasound and give them instant feedback.

Creative Destruction of Medicine
Creative Destruction of Medicine

Experience and clinical skill can help us a great deal, but even an experienced rheumatologist will get caught out from time to time!

Of course, Rheumatology isn’t the only application for ultrasound. Cardiologists were the first to embrace ultrasound and develop specific training courses. In emergency medicine, there is now a recognition that ultrasound can be invaluable for detecting a wide range of acute pathology e.g. intra-abdominal bleeding in a trauma situation. And quite apart from diagnostic use, ultrasound can help with gaining intravascular access, guiding liver biopsies and performing chest drains.

When I was trained in medical school, I was taught how to use a stethoscope in the same way as doctors had been for almost 200 years before me. I recognised that I couldn’t use this tool quite as well as a trained cardiologist, but as a screening tool it was still valuable. Now that portable and relatively affordable ultrasound is becoming available, should we not accept that in the near future most doctors will find some use for skills in ultrasound medicine? Out of hours in emergency situations when specialist ultrasonographers are not available, there are still many simple diagnoses that can be made by those with basic training. And what about screening for aortic aneurysm? At the moment this is patchy at best and many are still dying from ruptured aneurysms that could have been prevented. If we are to believe Eric Topol’s ‘Creative Destruction of Medicine’, we physicians are at risk of losing our ‘mastery’ of healthcare if we do not stay ahead of the game and adopt new technologies to make the most of our expertise. Topol describes how he, a well respected cardiologist, has set aside his stethoscope in favour of a smartphone sized ultrasound that allows him to diagnose simple valvular disorders. You can watch a YouTube video of the Vscan to see what he is referring to.

So it was with some excitement that I learnt that a medical school in South Carolina is actually incorporating ultrasound training into the medical school curriculum. Have you ever wished you could check your patient for an abdominal aortic aneurysm? Do you have twenty minutes to learn the basics about how to check for an abdominal aneurysm? Why not have a go and try the excellent basic course available online? It is currently available without charge and I think this is a great example of a clear and practical online course. Your scanning efforts probably won’t match those of a trained radiologist or vascular surgeon, but it will surely beat trying to diagnose an abdominal aneurysm using your fingers and a stethoscope! This course is provided by the ‘Society of Ultrasound in Medical Education’ who are trying to promote education in ultrasound among medical schools. There is also an enterprising group who have developed a series of online training courses in ultrasound for emergency medicine. You might argue that there is more than enough in the medical curriculum already. I would think that learning key skills should take priority over factual learning. Modern anatomy learning should surely now be based on the use of 3D imaging apps such as those from 3D 4 Medical, alongside dynamic ultrasound images and MR/CT images to supplement or replace the traditional textbook. This should help the student develop a better three dimensional and dynamic understanding of anatomy. A report on the four year experience of an ultrasound training programme for medical students in Carolina has recently been published – and the feedback from students was very encouraging. If they can achieve that in a four year programme, what is to stop our universities with five year medical courses from doing the same? app

Towards a Dataglove for Arthritis…

As rheumatologists we spend a lot of time examining the hands of people with arthritis. We examine them carefully for swelling and tenderness and use this information to assess disease activity. The effort to make this a more scientific assessment has paid off in the success of ‘treat to target’ protocols. This is fine for early arthritis, but there are other important dimensions of the problem we are only beginning to understand. Historically, rheumatologists have not been particularly interested in the scientific measurement of joint movement and function. This is a major gap in our understanding of arthritis and how it affects our patients from day to day. If we could better understand how stiffness affects joints, we could help our patients optimise their function and perhaps allow them to remain in work by testing different functional strategies in the workplace. Stiffness is also the forgotten member of the trio of symptoms that are widely regarded to reflect disease activity in rheumatoid arthritis. Technology has now reached the point where it should be possible to get accurate biometric data to record joint angles, movement and even touch. And technically it is now possible for these measurements to be recorded at home or in the workplace with minimal interruption to the normal routine. So enter stage – the ‘dataglove’. So perhaps it’s time to let our patients’ fingers do the talking…

The history of datagloves

The first wired electronic glove was patented by Thomas Zimmerman in 1982, and in 1989 Jaron Lanier patented ultrasonic and magnetic motion tracking technology to create the Powerglove. Lanier will also be remembered for coining the phrase ‘virtual reality’. The optical flex sensor used in the dataglove was invented by Young L. Harvill who scratched the fiber near the joint to make it locally sensitive to bending. The Power glove was designed for gaming but sadly for Lanier he was to lose control of the company VPL research. Interestingly, one of his VR predictions has been fulfilled: “Medical students could practice surgery on virtual cadavers that spurt virtual blood after a misplaced incision. Such uses are speculative so far, but few people doubt the technology’s potential”. Potential virtual reality applications in rheumatology include virtual homes or workplaces where the patient can explore functional problems and possible solutions. However, Lanier was well ahead of his time, and viable medical VR applications are still few and far between.

The Technology of Datagloves

The state of the art in current dataglove technology is represented by the 14-sensor 5DT dataglove ‘Ultra’ and the 22-sensor Cyberglove II. You can watch videos online of the 5DT and Cyberglove systems. At the moment these are powerful but expensive gloves which often require considerable effort to calibrate and customise. Working in conjunction with a team from the University of Ulster’s Integrated Systems Research Centre in Magee, we have done some work on programming and customising the 5DT Dataglove Ultra for patients with arthritis. Our work so far has focused on improving the repeatability and ease of calibration of the glove. We have also carried out work on the effect of using an thin inner glove – important in the healthcare setting to avoid problems with cross infection between patients. The 5DT dataglove uses optical fibre bend sensors. This technology is already fairly accurate, but has its limitations. We have therefore developed a new type of multi-functional dataglove using no fewer than 47 sensors. Our dataglove is designed to be used by people with arthritis by incorporating features to enable it to be easily put on and taken off. This will be tested in a group of patients with arthritis. We have also developed a user interface that will help patients calibrate the glove independently and use it accurately in the home setting.

project ‘digit-ease’

Our aim is to test the feasibility of using a sophisticated dataglove to take detailed measurements of joint position and movement in people with rheumatoid arthritis. We will test how closely the measurements match how our patients are feeling. We will be testing how much discomfort patients have in using the dataglove and how easy or difficult they find the visual interface. We hope that if the initial tests prove successful that we will be able to test the dataglove’s ability to detect changes in function after treatment.

For those of you who are interested in a little more detail, I have posted a copy of my recent presentation at the .med conference in Dublin on Dec 7, 2012 (#dotmed on Twitter). My co-workers James Connolly, Kevin Curran, Joan Condell and I have also recently submitted a paper for publication on the use of neural network theory to improve the accuracy of the data glove. I will provide a link if and when it is accepted for publication as this paper contains a lot more detail about our results so far.

High Fructose Corn Syrup: the killer ingredient?

Fructose has been introduced into our diet as a substitute for sugar, but it is becoming apparent that it can have pretty serious medical effects in the long term. The BMJ this week (27 Nov 2012) has an article on the intake of high fructose corn syrups (HFCS) in different countries. These products contain about 30% more fructose than the same weight in sugar. I was a bit shocked to see a box of Special K on the picture, so I thought I should investigate further.

So what medical problems can be caused by HFCS?

The first is obesity. The figure opposite shows the sort of correlation between HFCS intake and obesity. In the BMJ article it is stated that the annual consumption of HFCS per person in the US is 25kg (55lb) compared to less than 0.5kg per year.

The second is diabetes. The epidemic of diabetes in the US parallels the graph of increasing body weight.

A couple of other associated conditions include fatty liver and gout. For the rheumatologist both of these are relevant. Have you ever wondered why your teetotal patient on Methotrexate keeps getting abnormal Liver Function Tests? Maybe we should be pointing the finger at their HFCS intake. And the prevalence of gout in the US has rocketed roughly in parallel to the obesity epidemic.

But what about our own intake of HFCS? For those of us who smugly assume that our diets are pretty healthy, are you surprised to see Kellogg’s All Bran and Kellogg’s Special K on the naughty list of products with high Fructose content? Now before Kellogg’s sues me, I personally have not read the small print on the packet (I would need reading glasses to do so). I think it is possible that the ingredients of Kellogg’s products are different in the US/Canada compared to the UK, and on the UK website I certainly can’t find HFCS on the list of ingredients. And I’m not going to throw out my favourite cereals until someone can show me that they are to blame!




Watch out for that Grapefruit juice!

The idea that drinking a glass of fruit juice could treble the drug levels of certain drugs is a bit disconcerting. To then find out that this effect can persist for over 24 hours should be enough to make us even more concerned. This startling effect of grapefruit juice was discovered quite by chance. I suppose we can only be surprised and thankful that most people seem to survive perfectly well when they take medication in spite of these hidden perils. Some readers may find some parts of this blog post a bit technical at times, but for professional readers the extra detail is important to understand what is going on.

This interaction was discovered quite by chance in 1989 in a small study into the effect of alcohol on the absorption of Felodipine. In this study, grapefruit juice was used as a supposedly neutral ingredient to obscure the taste of alcohol, but when greatly increased drug concentrations were observed it became apparent that the grapefruit juice and not the alcohol was to blame.  The significance of these results wasn’t widely publicised until several deaths were reported due to the interaction.  In humans, bergamottin and dihydroxybergamottin are thought to be responsible for the “grapefruit juice effect”, in which these furanocoumarins reduce CYP3A4 mediated  metabolism of certain drugs. Grapefruit juice tends to have maximum effect on orally administered drugs whose bioavailability is severely restricted by the action of this enzyme.

From a Rheumatology perspective, what should we be aware of? Of course we should be aware of the whole list of drugs (which has now grown to over 80) – but here is a list of drugs commonly encountered in the rheumatology clinic

The most important drugs to remember are those that cause a major interference  with cytochrome CYP3A4, the gut enzyme that metabolises a large number of drugs.

The first of these is Ciclosporin, a drug sometimes used for treating Rheumatoid or Psoriatic arthritis. It is clear that drinking grapefruit juice causes a major increase in drug levels which can lead to serious toxicity. All patients taking this drug should be warned to avoid grapefruit and possibly Seville oranges (a common ingredient of marmalade). Avoiding grapefruit juice is mentioned in most of the patient information leaflets but we should also warn patients verbally when we prescribe it.

The second group of drugs affected by grapefruit is the statins (for lowering cholesterol). Among these, Simvastatin and Atorvastatin seem to be the main culprits – the increased drug levels can lead to an increased risk of myopathy and rhabdomyolysis (muscle injury). Pravastatin and Rosuvastatin do not seem to be affected.

It is much more difficult to get information about a number of other drugs that may in theory have a minor interaction with grapefruit juice. Among the drugs we commonly encounter in rheumatology, the following list of possible interactions can be regarded as possible but not confirmed (as far as I can establish):

Analgesics: Codeine, Tramadol, Buprenorphine, Oxycodone, Paracetamol
Others: Amitriptyline, Colchicine,  Oral methylprednisolone

As far as I know, the following drugs are not significantly metabolised by CYP3A4: Methotrexate, Hydroxychloroquine, Sulfasalazine, Leflunomide, Morphine, Prednisolone. The absorption of these drugs will not be affected by grapefruit juice’s effect o CYP3A4, but that doesn’t necessarily mean that they’re in the clear…

There has been a suggestion recently that Methotrexate levels could be affected by grapefruit juice. I am not sure how much evidence there is for this, but it does not seem to be via a CYP3A4 effect.

Grapefruit juice also has been shown to reduce the plasma concentration of several drugs. This seems to be caused by the juice inhibiting the organic anion-transporting polypeptide (OATP), which assists in the uptake of drug molecules from the intestinal lumen into the enterocyte. The inhibition of OATP by grapefruit juice would reduce the absorption of drugs transported by this transporter. Orange juice and Apple juice have been found to have similar effects on the absorption of some drugs. Methotrexate levels are thought to be affected by OATP transporters, which are found in the gut, the kidneys, the liver and a few other places. The net effect of these transporters is hard to predict, as they can have competing actions – sometimes enhancing excretion and sometimes reducing it. I am not sure that there is clear evidence that fruit juices cause Methotrexate levels to go up or down significantly, but the safest thing to do would be to avoid drinking fruit juices the day or two before taking Methotrexate.

What you have read here is an over-simplification of what is actually going on – there are other transporters such as P-gp involved in drug metabolism, and we really don’t know enough about how they work and how they are affected by elements in our diet or ‘complementary’ medicines. Time for the scientists to help out – please!


Drug Interactions with Grapefruit Juice: An Evidence-Based Overview

Suits you, sir!

Personalised Medicine for patients with Arthritis

Personalised medicine is the buzzword at the moment for the ‘genomics’ movement, but of course this has always been at the very heart of good medical practice. Everything we do should have patient care at the center,  individualised to the person as much as possible. There may be a few conditions – an under-active thyroid, for instance – where the treatment approach is likely to be the same for nearly everyone. However, for most of our patients with arthritis this sort of approach is not good enough. Even if we did have the best genetic test to allow us to pick the perfect drug for arthritis, the practice of good medicine would still require us to get to know the patient in a more holistic way.

For those of you who are just starting out in medicine, I’d like to share a few thoughts. Like most medical students I started out with a ‘list’ of things I had to ask and a standard ‘order’ for asking about different parts of the medical ‘history’. Whilst I certainly haven’t forgotten this important basic framework, it has been tweaked and modified over the years and I have learnt that it has to be adapted to the situation and to the person sitting in front of us. This is particularly true in the case of interviewing someone with chronic rheumatoid autoimmune disease, a complex condition which often impacts on every aspect of someone’s life.

There are a number of possible approaches to health problems, but for a scientific doctor the first step (after the initial introductions) is usually to try and understand the problem by establishing if the person has a recognisable syndrome or disease. If so, the doctor will take a careful history and carry out a detailed examination to try and establish a clear diagnosis within the major disease groupings. You need to be sensitive to the fact that in your anxious quest to get to the diagnosis as quickly and efficiently as possible you may inadvertently be directing and dominating the conversation, perhaps even interrupting the patient in front of you and ignoring some of the symptoms that are most significant to them. Many of the facts you need can be gleaned by just listening attentively to the patient telling the story in their own way with minimal direction. In the case of Rheumatoid arthritis, the doctor may use their clinical judgement and/or formal criteria to classify the patient as probably or definitely having that disease. It is important to establish a clear and unequivocal diagnosis as early as possible so that treatment can begin with disease modifying drugs like Methotrexate. In the past we might have been content with a broad diagnosis at this stage, but it has become more important to try and ‘sub-classify’ the disease on the basis of prognosis (i.e. how the disease is likely to turn out). We can try and assess if it is mild, moderate or severe on the basis of tests that predict the development of joint damage. This might include whether or not the person is positive or negative for Rheumatoid Factor or Anti-CCP (ACPA); how high the ESR and/or CRP is or whether or not the x-rays show erosion damage. This assessment of how aggressive the disease is likely to be will guide the physician as to how aggressive they should be with their treatment strategy. This information needs to be shared with the patient in a way that will allow them to come to the best decision about their treatment.

The second step in understanding the problem is getting to know the person with arthritis. In our medical student history-taking template this is relegated to ‘social history’, a section of the history that is often seen as less important and rather divorced from the main problem. A sense of empathy is particularly important here – can you really get a feeling what it would be like to be in their shoes? If you find this sort of approach alien to your scientific training, do take a moment to reflect on Jordan Grumet’s excellent blog and get a feel for how a physician can begin to get to grips with these issues. What do they think is wrong and what do they worry is going to happen to them (either because of the disease or its treatment)? What is their job and what does it involve? What is their home situation? What hobbies do they have? What aspirations do they have? Furthermore, how has the arthritis affected them? What activities of daily living do they struggle with? It may be helpful to think in terms of problems with ‘activities of daily living’ and problems with ‘participation’ in social, sporting or workplace contexts. With a chronic disabling condition like arthritis it is very likely to have an impact in these areas and if we don’t understand the problems we will not be in a position to help the person in need. Sometimes the most effective intervention can be a letter to the employer, a visit to an occupational therapist or physiotherapist. Some patients don’t have a particularly scientific approach to life, and may be more influenced by the story of what happened to the neighbour up the road. The attitude of the patient to drugs and medication is also important. When we prescribe drugs with quite a high risk of side effects, we need to be up front with patients and explain what might go wrong (including offering them an easy to read booklet). If they have never taken regular medication and are fearful of the possible consequences, we need to be aware of this and have a strategy to support them until they come to realise the benefits of effective treatment. If they have had a bad experience with a previous treatment, they may need more support and explanation the next time. As you can see, there are a lot of issues to discuss at a time which can be quite traumatic for the person with early arthritis. Ideally, this could be spread out over the first few weeks/months in a series of meetings with doctors, nurse specialists, occupational therapists, physiotherapists and specialist clinical pharmacists. This ‘multi-disciplinary team’ approach is well established, but it is important that they regularly meet together to ensure that they are all giving a unified message.

The next stage in understanding the problem is observing the response to treatment. We now recognise that in early arthritis, fairly frequent review is essential to get the disease under control. Most of the time we have to give drugs that are effective in about a half to two thirds of patients. We have no way of knowing who will respond and who  will be ‘resistant’ to treatment. It can be several months before we can tell whether or not a drug has not worked. That is a long time for someone with early arthritis. In the case of the anti-TNF drugs this ‘trial and error’ approach will expose some patients to several months of expensive and unnecessary treatment. We do know from research that there are some genetic differences between those who respond to these drugs and those who don’t. The stage is now set for the science of ‘pharmacogenomics’. Ideally we should be able to carry out a genetic test that will tell us if the patient is likely to respond or not. Since there are many genes involved in rheumatoid arthritis, this may end up as a battery of tests rather than just one. There are now several genes that have been identified which could help us develop such a test. Here in N. Ireland we are carrying out some research into this, using a gene test developed locally as well as using other possible biomarkers previously reported in the literature. Ideally, we would also be able to run a test to tell us which patients were likely to get the more serious possible side effects, but that’s another story!

Just to confuse things, someone has also coined the phrase ‘Personal Medicine’ to mean something rather different. This term is supposed to remind us that the outcome does not just depend on the skill and diligence of the team treating the patient. We need to inform but also to empower the patient by making them central to the decision making process and encouraging them to adapt in the best possible way to challenge their problems effectively. Chronic diseases have an almost inevitable effect on someone’s psyche – we adapt as things happen to us. Some of the coping mechanisms we develop are very helpful, others less so. This is why self-management programmes have been so successful in helping people cope more effectively with their problems. Kate Lorig can be credited for the important research that has shown these programmes to be effective not only for people with arthritis but also for those with a wide range of chronic diseases. Her programmes are used extensively by the NHS and charities such as Arthritis Care. Some physiotherapy programmes are also incorporating a similar light touch ‘CBT’ based approach to ‘kick-start’ the rehabilitation process. So perhaps the final stage of ‘personalised medicine’ is that the educated, informed and empowered patient works with the supporting multidisciplinary team to control their own condition.

The health practitioner needs to be attuned to the sort of coping strategies the individual patient has developed and be able to react quickly when things are starting to come apart. For doctors, these concepts should not be side issues. We can treat the disease and help people to feel much better, but to get effective changes in habitual behaviour we often need to take a more holistic approach. Doctors could do more to assess their patients and issue a tailored ‘safe exercise prescription’, an approach that has been very effective in Sweden. We also need to interested in the ‘end game’ – not just disease control but getting the patient back to their job or hobby, or perhaps giving them back their aspiration that one day they would learn how to abseil…



Stiffness: the forgotten outcome measure in Rheumatoid arthritis?

The history of measuring disease activity in Rheumatoid Arthritis goes back to the 1950s with the Lansbury Index and the Mallya and Mace Score. The Lansbury Index is incredibly complex to calculate but it was a serious effort at getting an objective handle on how patients were doing. He knew that his Index could also be used to test whether drugs for RA were effective. The Lansbury index incorporated morning stiffness, fatigue, amount of aspirin used, Grip strength, and ESR in a ‘systemic index’ as well as an ‘articular index’ which attempted to estimate the joint surface area. Lansbury was very careful in how he asked patients about their joint stiffness. He recommended that we should ask them what time they get up in the morning and then when they ‘limber up’ or feel less stiff. He published a paper in which he demonstrated that the duration of morning stiffness reduced as patients went into remission [Lansbury J. Quantification of the activity of rheumatoid arthritis. Recession of morning stiffness as patients go into remission. Am J Med Sci 1956; 232: 8-11]. The duration of morning stiffness was also included in the multi-component Mallya and Mace score. This score was validated in that each component was shown to be related to disease activity. I am not aware of any studies that have looked at the intensity of stiffness as a patient reported outcome measure, but it stands to reason that there might be a close relationship between the intensity of stiffness and the degree of disability. If I see a young mother whose stiffness prevents her from dressing herself or her children for an hour after she gets up in the morning I regard this as more suggestive of early RA than someone who complains of stiffness for four hours but without the same intensity.

Joint stiffness was excluded from the EULAR and WHO ‘core set of variables’ to assess disease activity, and so it does not feature in most of the commonly used disease activity scores in recent times. Some have even questioned whether or not the duration of morning stiffness reflects disease activity. It is certainly possible that other conditions such as Parkinson’s disease or oedema could cause a feeling of stiffness, and joint damage can certainly cause a complete loss of mobility. A brief review of past research would tend to support the claim that stiffness is indeed a valid marker of disease activity in RA.

In Hot joints1985 Hazelman and colleagues published a study using infrared thermography to provide a thermal image of the inflamed joints and derive a ‘heat distribution index’ for the larger joints. This technique must still be one of the most ‘direct’ measures of the degree of joint inflammation in someone with RA. Although this did not prove to be a practical test for the clinic, they did show that the heat distribution index correlated well with the duration of morning stiffness and other disease activity measures. The correlation with stiffness was just as strong as the relationship to joint pain. However, it is certainly true that many people do find it difficult to say how long their stiffness lasts for. People with severe disease activity may well have stiffness throughout the day. It is therefore not an accurate guide as to how active the arthritis is in an individual patient.

But what is joint stiffness, anyway? Like pain, it is a subjective phenomenon. It is difficult to define but may be regarded as a perception of difficulty moving a joint. So it is not quite the same as loss of movement. A joint that has been fused will often not feel stiff to the patient. Of course there may also be a loss of movement in a joint, for instance in a knee or elbow that won’t straighten properly. We do know that joints that are swollen and inflamed will often feel stiff to the patient, but we still don’t understand exactly what causes this feeling and why it should be worse in the morning. Is there a biochemical marker that correlates with the symptom of stiffness?

Assuming that stiffness reflects disease activity, could there be a better way to quantify the feeling of stiffness? This is a field where technological advances should begin to help. It is now technically feasible to measure movement accurately and have the data analysed and presented to the patient and/or their health professional in a meaningful way that can help to encourage health behaviour. This sort of technology should be able to provide accurate quantitative information about joint movement, which is clearly a very relevant outcome for people with arthritis. We are doing some research in this area, so hopefully there will be more to say about this in the near future!


Who should measure outcome – patients or health professionals?

One of the Internet’s foremost RA patient advocates Kelly Young (@rawarrior) has been blogging for several years about how doctors ‘consistently underestimate disease activity’. She has recently posted a further article about differences between disease activity scores carried out by patients and those carried out by doctors. She quotes a recent study which showed that the physician global assessment often lags behind the patient global assessment and in terms of joint scores patients often rate the swollen joint count higher than physicians. She highlights some important issues and we as doctors need either to explain ourselves or modify our methods. Do these discrepancies really arise because physicians are unsympathetic and are making light of their patients’ pain? In the interest of establishing a dialogue I will try and give a rheumatologist’s perspective.

Part of the problem may be due to a slight misunderstanding about how health professionals are using these scores. From the patient’s perspective, they usually want the score to reflect how good or bad they are feeling overall, which is entirely reasonable. There can be no argument that the patient is in the best position to know how they feel and this must always be respected. However, the health professional is likely to have a slightly narrower view of what a Disease Activity Score is supposed to reflect.

The main reason health professionals carry out disease activity scores is to assess the activity of a specific disease. When we use joint scores to assess disease activity, physicians tend to focus on the features that are more specific for a flare of inflammatory arthritis. We do recognise that sometimes patients feel worse at times because of another illness such as a viral infection or because they are depressed. The physician certainly needs to take this seriously and treat the underlying cause of the problem, but they should not assume that the problem is always a flare of RA. It is part of our job to recognise the difference between a real worsening of inflammation and something else that is making the patient feel worse. In the case of the DAS28 score, I as a physician am interested in a score that reflects as purely as possible the activity of the inflammation of Rheumatoid arthritis. And I do regard joint swelling as an important measure of the severity of active arthritis, because joints with synovitis are more likely to get damaged with erosions. It seems clear from recent research using ultrasound that synovial inflammation can sometimes be present in joints that are tender but not swollen, particularly in those with low disease activity. In a ‘treat to target’ strategy, the DAS28 score is used to make important decisions about escalating treatment. The DAS28 score does give priority to patient assessment – the patient global assessment is included rather than the MD assessment, and the tender joint score is weighted as more important than the swollen joint count. I don’t use an MD global score, but sometimes if a patient seems to underestimate their disease severity I will ask them if they really mean to give themselves such a low score.

Swollen joints are also a crucial finding when health professionals are trying to establish a diagnosis. When I am trying to establish a clear diagnosis of early inflammatory arthritis, I am looking for certain types of swollen joints. I am specifically looking for fluid in the joint or soft boggy swelling. I am not interested in joints where the bones are swollen (osteophytes), because I know that this sort of damage is typical of osteoarthritis and does not respond to disease modifying drugs. I will certainly look for tendon swelling and dactylitis but I am not going to count this as joint swelling. Detecting small amounts of swelling is not easy, and in difficult cases I will use an ultrasound to help me detect small collections of fluid or thickened synovium: this is particularly useful in people who are overweight.

Studies have shown that when patients carry out the swollen joint count, the results can be different from physician scores. We have already seen that some physicians are cautious about counting joints as swollen when the swelling is bony. In these cases the patient scores may be more accurate but it may not reflect the amount of inflamed synovium as closely as the physician score. I would argue that a swollen joint count based on a combination of examination & ultrasound is the most accurate method we have at the moment. Whilst most patients have a very good idea of how swollen their joints are, there are situations where they are not so sure. Patients with Fibromyalgia syndrome will often complain of swollen joints even though others cannot see or measure any swelling. This may be due to a phenomenon similar to the way our lips feel swollen after a trip to the dentist.

I think that currently the Disease Activity Score is the best compromise between the patient and physician perspective. In essence I believe that the health professional and the patient should still carry out the assessment as a joint effort. Physicians and health professionals need to pay very close attention to the patient’s assessments and deal carefully with any problems identified. It is important that they communicate with patients about what the scores mean and make it clear that they are not making light of their pain. More research needs to be done on the value of formal assessment of severity of fatigue and stiffness symptoms so that we can decide whether or not inclusion of these features would help to improve the assessment of disease activity in Rheumatoid arthritis.

When is a DAS28 NOT a disease activity score?

I’m a big fan of the Disease Activity Score (DAS) and if you’re interested at all you should check out this excellent article in ‘The Rheumatologist’ about how Piet van Riel and Desiree van der Heijde developed the score. As much as I like this tool, I think people need to be aware of its limitations in clinical settings. There is no such thing as a perfect disease activity score, and similar problems arise with other scores. I use the DAS28 (ESR) regularly in clinic, and for the majority of patients it is a very useful tool that matches what the patient and physician think is happening to disease activity. I am written this article mainly for clinical health professionals in Rheumatology.

…when the patient has Fibromyalgia (as well as RA)

This one may be a bit obvious, but it can catch out the unwary. I have made this mistake more than once. As many of you know, the incidence of FMS is increased in chronic diseases like RA and SLE and it can seriously skew the DAS28. In a busy clinic we can be so busy doing the DAS28 and sorting out the patient’s problems that we don’t check for muscle tenderness in a patient with known RA. So how can we avoid this mistake? If you see a patient where the tender joint count and VAS scores are very high but the ESR and swollen joint counts are low/normal – look out! This is the typical pattern with FMS symptoms. A quick check for muscular tenderness will usually confirm your suspicions. Of course, the symptoms of pain and fatigue are genuine and need to be addressed, but just not with anti-TNF drugs or more Methotrexate! You are welcome to check out my little shared spreadsheet tool on Google Drive that shows the COMPONENTS of the DAS28 as slices in a pie chart. This tool uses the official formula for DAS28 (ESR) but splits up the components and allows you to experiment with different values and see the results. It makes it a lot easier to see when the Tender joint score and VAS score are dominating the DAS28.

…When the patient has more tender than swollen joints

I’m not going to make a big issue of this, but it is good to be aware that the DAS28 score puts twice as much emphasis on tender compared to swollen joints. This is good in that it makes the DAS28 more of a ‘patient reported outcome measure’ but not so good when you see a patient with quite a few swollen joints and an inappropriately low DAS28 score. And do remember that the DAS28 was not developed to be used in a system where there would be a clear incentive from having a higher score (i.e. access to biologic drugs) – it is open to some bias on the part of both patient and physician.

…When the patient has a low esr

The DAS scores were developed using data from clinical trials. With handy calculators around, most people don’t pause to check the formula. The ESR score is log-transformed to take account of the way an ESR rises. This is all very reasonable, but it has to be remembered that patients were selected for these clinical trials because they had very active disease with a lot of tender and swollen joints. In most of the trials the starting ESR was very high. The ESR during the trials fell significantly but often not to ‘normal’ levels. So the DAS28 was not really properly validated in the population of RA patients we see day to day in clinic: those with fewer active joints and low/normal ESRs.  Which do you think would cause a greater change in DAS28 score: a change in ESR from 40 to 20 or from 15 to 2mm/h? The change in DAS28 score is actually three time larger in the latter example – a reduction of 1.51 – greater than the NICE/BSR ‘response’ criterion for biologics. There is no cut-off for ESR values within the normal range, and even insignificant changes.

In the UK, NICE guidelines dictate which of our RA patients can get access to biologics. The ‘cut-off’ for access is a DAS28 score of over 5.1. This may be no problem for most patients, but for some men with particularly low ESRs this is an issue. I have a couple of patients who have definite ultrasound proven synovitis in multiple small joints but a low ESR of 2mm/h. Now I challenge you to try and get a DAS28 of 5.1 with that! Have a go on the DAS component spreadsheet. Try entering 15 tender, 15 swollen joints and a VAS score of 90. Now this doesn’t affect a lot of patients, but there’s a handful in our department who need treatment but can’t get it because of this.

…When the patient is in ‘Remission’ (DAS28 less than 2.6)

I would guess that most of you are already aware that the DAS28 doesn’t work too well when it comes to defining remission. This is partly because it completely misses out joints such as the feet and ankles which can be important to people with partly controlled arthritis. It is also partly because of the under-valuing of swollen joints (mentioned above). One of my patients had 5 swollen joints, no tender joints, ESR of 8, and VAS of 10. His DAS28 is 2.23 (i.e. in remission). I think it is better to use the new ACR/EULAR remission criteria.

…When it is done by someone inexperienced

Once people have learned how to examine the patient properly to complete the score and practiced using it regularly for a few weeks they will be able to get quite repeatable results. There is an instructional video on the official website http://www.das-score.nl/ and this site also contains a list of the ‘official’ reference articles on the various DAS scores. However, there are grey areas and there can be quite a bit of difference between observers. So if we’re checking DAS28 scores regularly in clinic, it is a good idea to have it checked by an experienced observer rather than a trainee. If we’re relying on a crucial result (e.g. to determine if a patient is to get biologic treatment or not) we need to make sure that the person doing it is experienced. To measure ‘response’ it is best for the observer to be the same person before and after.

So that’s it. All my moans about the DAS28 all in one page. Am I the only one who has these issues?

Why Bother Measuring Outcomes in Rheumatology?

You can’t bank on the outcome

Daniel Berriman

For a many years we Rheumatologists relied on clinical judgement to decide how our patients were doing. We tended to assume that this would result in the best outcome for our patients. Actually, we weren’t doing nearly as well as we thought. Most of us were aware of disease scoring methods, but we regarded these scores as mainly for use in research. Things are changing, and it is high time both patients and doctors had another think about outcomes and how to measure them.

When we talk about ‘outcome measures’ in arthritis, I would guess that some people might wonder what we’re on about. What is an outcome when there’s no income, I hear you ask! Some people may be more familiar with the terms ‘bottom line’ or ‘end product’. Just as in business, if we want to improve our effectiveness or efficiency at treating people with arthritis, we know that we need to not only ‘measure’ what we’re doing but also set targets. There is now a mounting body of evidence to support a ‘Treat to Target‘  approach to RA treatment. This strategy involves changing treatments every time Disease Activity Scores go above a certain level. This ‘aggressive’ approach to treatment is more likely to achieve ‘remission’ or a ‘low disease activity state’ than the traditional approach. It is reliant on the regular use of outcome measures which determine the target to aim at. But what exactly should we be measuring and how should we do it?

Most people who attend Rheumatology clinics have arthritic conditions where there is joint inflammation and/or damage. We can speak about ‘pathology’ meaning that there is something abnormal going on in the tissues in and around the joints. So one of the things we need to measure is how active the disease is and how well we are doing at reducing the disease activity. In the early stages of inflammatory arthritis, there is still some hope of a full remission if the inflammation can be controlled. However, we also know that prolonged periods of inflammation in a joint lead to damage, so we also need to measure the severity of joint damage. Once a joint has been permanently damaged, completely controlling disease activity will not be able to restore the joint to normal and the chance of a full recovery is lost. We need drugs that not only reduce disease activity but also reduce damage. We must not assume that drugs that reduce inflammation will also be effective at stopping joint damage. At some point we will also need to target ‘prevention’ or ‘cure‘ as outcomes. At the moment we can’t claim to have cured any type of arthritis with the possible exception of gout. Of course we mustn’t forget that RA is a systemic disease, so there are other aspects of disease activity we may not be measuring (such as anaemia).

Diseases are only important to people if they have an impact on how they function, their ability to work or do normal daily activities, their quality of life, or if they increase the chances of dying prematurely. Treatments are of little use unless they result in an improvement in some of these outcomes. Twenty years ago the available treatments for arthritis had – at best – a roughly 50-50 chance of making the patient feel better but also a one in three chance of causing unpleasant side effects. In recent years, there has been a shift away from over emphasis on disease related outcomes toward ‘patient related outcome measures’ (PROMS). Many of these outcomes are common to most diseases, so we can compare how the quality of life of a patient with arthritis compares with that of a patient with another condition such as chronic lung disease or chronic Heart Failure. It has to be remembered that many patients suffer from several conditions, so these outcome measures may reflect the influence of other diseases as well as arthritis. I don’t think there would be many doctors who would suggest that we should measure PROMs without any reference to disease related outcome measures because we do need to keep our focus on tackling the underlying disease.

Finally, we shouldn’t forget the importance of ‘patient satisfaction‘ as an outcome and (on a population scale) the ‘health economics‘ of the intervention.

Measuring outcomes takes time. Outpatient clinics are busy. It is easy to recommend that everyone should have three or four outcome measures checked every time they come to clinic, but it is not so easy to do this when the clinic is running late or when the patient comes in with a long list of questions. Rheumatologists are used to seeing outcomes reported in the medical research literature reporting whether or not an intervention is effective. It is only very recently that it has become generally accepted that recording a disease activity score such as the DAS28 should be routinely recorded for RA patients at every visit to clinic. A recent Spanish survey reported at EULAR 2012 suggested that the DAS28 score was being recorded about half of the time in clinic.

This is the first in a series of articles about how patients and health professionals can make sense out of the existing disease outcome measures and how things are likely to change for the better in the near future…


What’s on my eBookshelf at the moment

Lounging in cyberspaceOver the past few months I have spent some time investigating the possible benefits of social media and technology for the practice of Rheumatology.

I have found Twitter useful not just for communicating with other Rheumatologists, but also for engaging with patients and charity groups. I much prefer ‘curated’ digests of recent research to wading through long lists of journal articles (thanks to @amidauhoo, @doctorakerkar, @irheuma, @rheumatologe, @rheuma_suffolk, @Thearthritisdoc, among others). It is also convenient to be presented with links to useful articles or resources, particularly the full text articles. The ability to get immediate feedback on what others think of research findings that ‘might’ change my practice adds a new dimension and helps me to get to grips with the practical implications of the research. This is a sort of post-publication peer review by people who are actually in clinical practice rather than wrapped up in full time research. The 140 character restriction is a bit of a limitation, and I wish it were easier to move quickly from a Twitter discussion to one on a forum/google groups/linkedin. Although there is a pleasing immediacy about these Twitter debates, people who come to the discussion half way through will be less likely to join in if they haven’t seen the original question. I know that a lot of us blog from time to time, but some people do have a real talent and are worth going back to: some of these medical blogs are now on my regular reading list and I appreciate the Twitter updates that point to new blog articles. I’ve been finding that more people are commenting on blogs within Twitter and at although this often generates an immediate reaction, at the moment this doesn’t link up with the comments on the blog site. Some of the blogs are directed at patients, some at professionals and some are a bit ‘indeterminate’ in terms of focus (including my own). I have to admit that at the moment I am still a little wary of any detailed interaction with patients but this is an area I would hope to develop a little once I have a bit more experience. Patients have a lot to offer and are often very passionate about their condition. It is natural that sometimes reticence on the part of the health professional will be interpreted as coldness or indifference, but it is hard to get across some of the professional pitfalls we have to be wary of.

Who do I follow on Twitter (professionally)?
One of the reasons that I decided to spend some time using Twitter is because Ronan Kavanagh (@RonanTKavanagh) encouraged me to get involved. I don’t actually know most of the people I follow on Twitter although I look forward to meeting them in person at ‘tweetups’ during some of our professional conferences. Since the Twitter Rheumatology community is still quite small, we quite quickly get to know our new members, exchange a few messages and build some rapport and support for each other. I have tried to follow all of the English-tweeting Rheumatologists that I’ve come across, as well as some patients and charities who have followed or commented on my twitter posts. I have also been following some GPs in the rest of the UK such as Dr Ann Marie Cunningham (@amcunningham) who is interested in the use of SoMe in medical education. Through some of these contacts I have gained an insight into wider NHS debates and discussions about GMC guidelines etc. I have also found out about sites such as ‘@medgadget’ which keep me up to date with wearable technology and its potential applications in medicine and rehabilitation. I am also enjoying following Rheumatologist Martin Lee‘s (@martin_kayaking) epic kayak trip around Britain on Facebook and Twitter daily updates keeps everyone interested. He is raising money for NRAS, a UK based RA charity. I also follow @kevinmd, @Doctor_V, @westr and @hjluks – all of whom are seasoned experts in social media in medicine. Howard Luks is an orthopedist and particularly helpful to Rheumatologists. For a bit of fun, try checking out the irreverent medical rapper @zdoggmd!

My most often used Twitter hashtags: #rheum, #rheumedu, #hcsm, (unofficial: #spondylitis, #ankylosing, , #rheum2012, #TMED4). Hashtags help to organise tweets for interest groups or conferences. They can be registered at @symplur

I haven’t yet used Google+ or Hangouts, although they look to be valuable tools for medics with better security and ‘boundaries’. Among our select group of Rheumatologists Carlo Caballero @carvicab is an expert in this area. Ronan has also set up a list of Rheumatologists on Twitter called ‘Rheumatologistswhotweet‘.

[Update 2013] Chetan Narshi (@rheumi_) led the tweeting as the official @RheumatologyUK #Rheum2013 conference tweeter along with James Bateman (@jamesbateman). Other notable tweeters at #Rheum2013 @tinydaff, @DrAiLynTan.

Blogs (Ronan Kavanagh; Jordan Grumet). Consistently high quality blogs. Ronan’s new website is state of the art in terms of design, but the content isn’t bad, either. Jordan Grumet provides reflections that are very well written and thought provoking. I get RSS feeds to update me on new posts in case I miss them on Twitter. I dip into other blogs if I think they are useful at the time. There’s some great stuff out there and I don’t have the space to name all of the good ones!

Books (Eric Topol: Creative Destruction of Medicine) – Recommended to me through Twitter. This cutting edge and somewhat provocative book has stimulated me to learn more about genetics/genomics and broader applications of technology in medicine (which had been one of my interests, albeit in a narrower field). You can also follow @EricTopol, regarded to be the most influential figure in medicine in the US at the moment.

iBooks (PDFs or interactive iBooks)

Presentations/Prezis (Bertalan Mesko: @Berci has spent an enormous amount of time preparing his social media course at Webicina.com. At the moment this is completely free!). The social media course is a particularly impressive piece of work, and Berci has also curated material in a wide variety of disciplines. Why not have a go at creating your own Prezi and share the result with your admiring colleagues/trainees?

My favourite General Tools

      Twitter for ipad (3/5)
      Tweetbot for ipad (4/5)
      Tweetdeck (on PC) (4/5)
      Evernote (4/5)
      Goodreader (PDFs): 4/5
      Instapaper 3/5
      Feedler (RSS feeds) 3/5
      WordPress for ipad (2/5)
      Prezi viewer (3/5)
      Documents to Go (1/5)
      Mindmaps (3/5)

Medical Apps

  • Epocrates – the most popular medical app, a great free resource for information about medication. It is unfortunate that it is only US based as they ditched the UK list of drug names some years ago.
  • ISpondylitis (Irwin Lim & colleagues) – So far, I’ve only looked at the free version – the animated exercise section is particularly amazing! Please get this app and let Irwin know what you think. There’s a lot of work has gone into this development and I hope there will be more apps like this from Rheumatologists.
  • NASS: Ankylosing Spondylitis – Again, an excellent resource with animated exercise. Best of all, there could be a local NASS charity group near you (& your patient). Get this app and support the work they are doing!
  • Medscape – CME portal; App for iPad good medication resource
  • Das28 app (although I tend to use the web based DAWN DAS28 calculator)
  • Drchrono (I haven’t used this yet)
  • MyRA

So that’s it: a quick review of what’s on my eBookshelf at the moment. Apologies if I’ve left anyone out. If you’re a Rheumatologist why don’t you share your own experience? You’d be welcome to submit a guest post here about how your practice has benefited from your use of online resources.