An alternative perspective on the challenges facing science today
I am excited to share that as a result of my previous blog post "Can infection cause chronic disease?", I was invited by the World Health Organization's (WHO) Non-Communicable Diseases office to contribute to a WHO report on Men's Health in the European Region!
The report is a comprehensive analysis of the various health challenges men face, the current state of health systems underpinning those issues, and provides proposals on further research and the policy changes necessary to improve the outlook for men's health in Europe.
If you would like to read this report, go to the link below, and you will see my name in the acknowledgements page. www.euro.who.int/__data/assets/pdf_file/0007/380716/mhr-report-eng.pdf?ua=1
I would like to thank Dr. Kremlin Wickramasinghe at the WHO for this opportunity, and I hope this report will have a far reaching impact in health policy.
Update: An edited version of this article has been published by Antibody Genie. Thanks to Dr. Colm Ryan for the invitation. Check out the article here: www.antibodygenie.com/blog/can-infection-cause-chronic-disease/
With non-communicable diseases (or NCDs, which include heart disease, diabetes, cancer) now responsible for the most deaths worldwide, large investments into research on these diseases are helping us understand their causes. Many of these diseases have something in common, they involve chronic inflammation. Cells normally triggered by the immune system to fight infection, are persistently activated by factors produced within the body (endogenous factors), eventually causing damage to bodily tissues and beginning the disease processes involved in the development of diabetes, cancer and atherosclerosis - the build-up of fatty plaques in the arteries causing heart attacks and strokes. This begs the question, if both infection and endogenous factors can trigger the same immune responses that are known to cause NCDs, could infection directly cause NCDs?
Triggering our immune defences
A good example of the responses triggered by both infection and endogenous factors starts with the well-characterised family of Toll-like receptors (TLRs), which are found on the surface of many immune cells. These receptors play a key role in innate immunity – the first line of defence against infection. Each of the 9 members of the TLR family recognise different components of pathogens, for example TLR4 recognises lipopolysaccharide (LPS) found on the outer membrane of certain types of bacteria, and TLRs 3 and 7 recognise viral ribonucleic acids or RNAs, which viruses release into the host cell they infect to exploit the cell’s machinery to produce its damaging viral proteins. When TLRs bind to a molecule they recognise, they can activate a sequence of proteins ending with a protein called NFkB (NFkappaB) and/or the Interferon regulatory factor (IRF) family, which are responsible for the production of numerous inflammatory proteins . Once an immune response is triggered following TLR activation, it is usually sufficient to successfully destroy the infection. Thus, the infection is short-lived and the immune system can return to a resting state.
Your cells die every day. Don’t worry, your body is protecting itself. In a process known as apoptosis or programmed cell death, cells that are no longer needed commit suicide. Some cells are only required for a short time, they maybe infected by a virus or develop harmful cancerous mutations. Cell death is also an essential part of development from an embryo. For example mouse paws begin as spade-like structures and only form the individual digits as the cells in between die . During apoptosis the cells fragment into smaller apoptotic bodies, and their cell surface is flipped open to display lipid molecules called phosphatidylserines, which act as an “eat me” signal to recruit cells called macrophages to engulf them, before their contents spill out and damage the surrounding tissue. This is a process known as efferocytosis.
However cell death is not always so orderly. Some cells suffer premature death known as necrosis, where they burst open for various reasons such as infection, physical trauma or extreme temperatures. However as the cell’s contents are released into the open, an inflammatory response is triggered, so the macrophages sent to engulf these cells release substances that can damage the surrounding tissue, resulting in a build-up of dead cells.
It is this damaging chain of events that often occurs in atherosclerosis; the build-up of fatty plaques which can block arteries or trigger blood clots leading to heart attacks, strokes or tissue death, known as ischaemia. As fatty lipid molecules (primarily LDL or ‘bad’ cholesterol) build up in arteries, they act like damage signals. Macrophages recognise these damage signals as if it is phosphatidylserine, and engulf the lipids to become what is known as a foam cell; a cell full of lipid. A healthy macrophage can repackage the LDL into larger HDL cholesterol, which is released back into the bloodstream to be excreted by the liver. The foam cell can also leave the atherosclerotic plaque to be disposed of via lymphatic vessels, thus shrinking the plaque.
However, foam cells can be overwhelmed by engulfing excess cholesterol, increasing harmful inflammatory signals, stress and apoptosis. But all is not lost here. If other macrophages clear the dying foam cells, less harm will be done. The problem is the increased inflammation renders efferocytosis defective, resulting in a process called secondary necrosis. Here apoptotic bodies swell and burst open, as they haven’t been cleared in time. As a result, a large amount of cell debris builds up inside the atherosclerotic plaque, creating what is referred to as a necrotic core. The core is pro-thrombotic when it is exposed to clotting factors in the bloodstream.
December 12th 2014 was declared Universal Health Coverage (UHC) Day worldwide as 587 academic institutions, non-governmental organisations and health charities campaigned for healthcare to be universally available so that epidemics such as Ebola, Malaria and Heart Disease can be tackled, particularly in developing countries. This movement has been inspired by successful healthcare systems in developed countries, which have improved the health of their populations while also boosting their own economies as a result of a healthier workforce. One such paradigm is the UK’s National Health Service (NHS). Founded in 1948 by the Labour party, it is now the largest publicly funded health service in the world, and was recently rated the best health service amongst 12 developed countries.
Since the Health and Social Care Act was passed by the Conservative and Liberal Democrat coalition government in 2012, there has been increasing concern that the NHS will not be a ‘free-for-all’ health service for much longer. We have already witnessed nurses losing their jobs, hospital A&E wards being shut down and surgical procedures being curbed in an effort to meet the government’s demand of £20 billion in savings by this year. It is no wonder, as the NHS actually requires another £30 billion each year to stay afloat by 2020. A study in the British Medical Journal last year showed that private sector providers secured 33% of NHS contracts in the preceding 12-month period . It was even discussed that GP consultations should require a £10 charge, although the British Medical Association rejected this motion. It seems profit will become and increasingly influential factor in the provision of health services in the years to come, thus the NHS may struggle to maintain its status as the gold standard for the provision of healthcare worldwide. This is perhaps driven by an American-style mentality where any socialist system is feared as an attempt by government to control the population. As NHS services are slowly eroded, so too will the health of the UK population, the ability of the UK to remain a world leader in medical innovation, and the strength of Britain’s economy.
So what if the NHS became inaccessible or unaffordable to the poorest in Britain? We have seen the havoc created by private insurance companies in the US and elsewhere, who often reject ‘high-risk’ patients deeming them too costly. Hence the poorest and most vulnerable in society cannot afford healthcare they so desperately need. However other patients are not safe either. Deceitful persons can exploit them due to their lack of medical knowledge. This scenario has been particularly evident in the Indian states of Madhya Pradesh and Uttar Pradesh, where an inefficient healthcare system has allowed exploitative companies to run riot .
Let’s take a look at how universal healthcare has benefited developing countries. There are many examples where good basic healthcare has been provided at a very low cost. In 2001, Thailand introduced a nationwide system where no patient would have to pay more than 60p per visit for medical care, while the poorest quarter of the population were exempt from charges . As a result mortality rates, particularly in children, have fallen while life expectancy has risen significantly. The new Thai health system has also demonstrated that with widely available preventative care and early intervention, the need for expensive treatments and surgical procedures has plummeted. Readily available healthcare is also essential to fight infectious disease epidemics, should one ever arise in the UK. We have seen in Western Africa that if countries surrounding Guinea, where the most recent Ebola outbreak began, had effective universal healthcare systems, this could have alleviated the outbreak or even prevented Ebola from spreading throughout the region. This is why Nigel Farage’s shameful comment on HIV diagnoses in the recent seven party election debate was so short-sighted, in addition to being entirely false. If we were to reject treatment for HIV patients born overseas, we would be leaving the door ajar for HIV to be readily transmitted within the UK population as well as in surrounding countries, facilitating what is already a global pandemic.
There is no doubt that social inequality needs to be addressed to tackle some of the country’s major health burdens, something the major political parties seem unwilling to confront. The poorest in society are more vulnerable to harmful behaviours such as smoking, abuse of alcohol and drugs, and mental health problems. Anxiety and chronic stress caused by redundancy and poverty can weaken the immune system and increase risk of cancer and cardiovascular disease. But a strong universal healthcare system plays a large role in tackling inequality, while benefiting the economy. This has been evident in the once comparatively poor Indian state of Kerala, where universal healthcare and schooling has helped the state achieve the highest per capita income among all Indian states . Cuba has been subject to US sanctions for several decades, but it has one of the highest doctor to patient ratios and vaccination rates in the world, and life expectancies are similar to the US population. Cuba is even able to offer help to other countries by flying out doctors to scenes of natural and humanitarian disasters.
The Lancet recently published a proposed manifesto to improve five key areas in the NHS :
· The currently poor interface between general practice and A&E medicine.
· The modest way child and adolescent health care is delivered.
· End the false dichotomy between mental and physical health.
· Stop neglecting early diagnosis and prevention.
· Act on elderly and social care.
It has also been argued that other measures need to be taken to make GPs more accessible such as extending GP opening hours, and making appointments available online and by phone .
I have already explored how the NHS is vital for the UK to maintain its status as one of the greatest medical innovators in the world . Such innovation is essential to tackle major problems of the future such as the prevalence of antibiotic resistance and treating the ageing population who often suffer from a multitude of conditions requiring careful management. Innovations include the development of genomic medicine and healthcare technologies such as wearable devices and smartphones. In the last five years, the current government has frozen research budgets, resulting in a net loss of funding due to inflation. There is an emphasis on investing in the ‘Golden Triangle’ of London, Oxford and Cambridge, which needs to end. Investing in other parts of the country would not only benefit science, but also health, economic and social regeneration . We also need the NHS to train our future doctors and innovators. However this has been compounded by the recent hike in tuition fees, resulting in fewer applications to university among A-level students.
Climate change is also a major threat to the health of the global population. Insect-borne diseases could come closer to home, extreme heat can kill those with existing heart and lung problems, pollutants can increase the risk of lung cancer heart disease, and the loss of homes and livelihoods due to floods or droughts can cause depression . Such a threat requires action on a global scale. While it is encouraging that the UK has increased its international development budget to 0.7% of GDP, more advocacy work is required by the UK to act as a leader in advancing universal healthcare globally .
So as we reach the final month before the UK’s general election, who can we trust to bring about the changes the NHS needs? We have already witnessed how the current coalition government, headed by the Conservatives, have introduced a culture of austerity and privatisation that has sent pulses racing among ordinary citizens. The results of more encouraging measures, such as a pilot scheme where opening hours in 14% of GP practices were extended, are yet to be seen. In their election manifesto, the Labour party have pledged to recruit 8,000 more GPs and guarantee an appointment within 48 hours. This maybe a far reaching goal as the largest increase in the number of GPs in any parliamentary term in the last 20 years was 5,414, while the last Labour government was only able to deliver their guarantee of an appointment within 48 hours to 81% of patients . However their pledges are a step forward, and could be better than anything we could ever hope for from another five years of Conservative leadership.
British Prime Minister David Cameron recently announced that those individuals, who refuse treatment for their obesity, alcohol or drug problems, could have their sickness benefits cut. Such a statement appears to stem from a view that these individuals intentionally neglect themselves, and that punishing them will deter such behaviour in the future. The reality is very different.
We all know that obesity is the result of excess consumption of foods with a high content of sugar, salt and fat. Alcohol and drug addiction are often due to an individual’s desire to seek comfort and relief, perhaps to escape from difficult personal circumstances such as redundancy or losing a loved one. But it is the introduction to these foods and substances that is the real issue, and what is responsible for this? Advertising.
In the Western world, and now becoming increasingly common in developing countries, we are bombarded by billboard, television and newspaper adverts for all types of fast food burgers, alluring chocolates and “invigorating” tipples. You probably haven’t realised this as you go about your everyday life. Have you ever walked past a patisserie window without wanting to stuff your face with cake? Children are particularly prone to giving in to such advertising. If you give in to your senses and devour such unwholesome grub, you will be left wanting more. In fact, excess sugar and salt intake, in addition to alcohol and drug consumption, increase the activity of dopamine neural pathways in the brain, commonly viewed as a reward circuit in the brain. With this level of temptation surrounding us, it is no wonder that some individuals fall victim to a vicious cycle of cravings and bingeing, much like the addictive behaviour observed in alcoholics and drug addicts. In addition, the low cost of fast food makes it a more affordable option than healthier alternatives, for those who maybe struggling with their finances.
There also lies a cultural problem, particularly with regards to alcohol consumption. Alcohol is widely seen as an essential ingredient to engage socially, by abandoning one’s inhibitions and leaving behind the woes of life. Coercion from peers can often lead to one consuming alcohol when they are otherwise trying to abstain, or risk being excluded from the social circle all together. Moreover advertising by alcohol brands glamorizes beverages with the use of celebrity endorsements and images of partying hard. While many do drink responsibly in social environments, binge drinking is on the rise - which has been proven to have detrimental health effects such as brain damage in teenagers, and muting one’s immune responses to infection. And if an individual were to unexpectedly face difficult personal circumstances, they could see alcohol as a source of refuge – due to its ‘positive’ image - and attempt to drown their sorrows. The fact is alcohol will only provide temporary respite from such problems. It is not the solution, and so the despair deepens.
When we consider all of these points, it is clear that people suffering from addictions need help, punishing them by withdrawing their benefits is not productive in the slightest. It will only send them into deeper despair, exacerbating their harmful behaviours. These patients require strong psychological support from the health service as well as those closest to them.
We must also bear in mind that these patients may be suffering from other health problems that could be causing or complicating their health, preventing them from working and exercising, such as diabetes, arthritis or accidental injuries. In these circumstances, it is highly unlikely that obese individuals will refuse treatment. These patients require careful and rigorous management of their health, of which only qualified health professionals can provide.
This debate underlines the argument that good health is a human right. An individual’s personal choices and financial circumstances should not be detrimental to their health, especially when the environment surrounding them heavily influences such choices. Providing the best support possible for these patients can only be beneficial for the country, by potentially allowing them to return to work and contribute to the UK economy. On the other hand an oppressive approach, coupled with the reduction in quality and quantity of NHS services is neither beneficial for patients or the economy.
This piece was written for The News Hub. Please visit https://www.the-newshub.com/health-and-fitness/punishment-is-not-the-answer-to-health-problems and give it a vote up!
Lessons from the Standing Up for Science Media Workshop in london organised by Sense About Science
Do you know what the following claims have in common?
I hope you have realised that none of these claims have any substantial evidence to support them, so we can safely assume they are false [1,2]. Everyday we are bombarded by adverts and stories in the news detailing the latest scientific advances and companies selling their newest health and beauty products. How can us scientists ensure the wrong information does not reach the public?
The mainstream media is often criticised for biased reporting of current affairs. They have also angered many scientists for dumbing down the science when reporting about newly published studies, or even distorting the main findings to support one’s agenda, perhaps politically motivated. Quite unexpectedly tabloid newspapers can be more accurate at reporting science stories than broadsheet newspapers. While hyping up a study, as “the next miracle cure for cancer” will undoubtedly garner attention and increase newspaper sales, their intentions are not always so covetous. Newsrooms are incredibly competitive environments, so the pressure to release an attractive story can be so immense that erroneous reporting can slip through. Journalists actually do welcome help to interpret the latest studies, after all they are not trained scientists, so how can we expect them to critically analyse data from a study like a trained scientist can! And it is incredibly damaging for a journalist in the long term if they become known for misreporting a study, as scientists will not trust them if they receive a request for interview. Journalists often use #journorequest on Twitter to find experts to help them on a story.
How can you ensure the main message of your study doesn’t get lost in the media hype? If your study gains massive media attention, be prepared for interviews, and have three clear messages that you can repeat. Learn to speak in repeated sound bites, as you generally do not have much time to have your say. As you are the expert of the study, be prepared to engage with people with all levels of intellect. If you believe your study is not receiving the attention it deserves, then get your word out there. Practice writing about your study in a short but interpretable manner, as if it were a newspaper headline. Even try writing and circulating press releases to get yourself known and trusted in the media as an expert in your field of research. When writing your press release, target it towards a journalist specialising in scientific reporting. It also pays to go to your university press office and talk about your research; they like to hear from active researchers. However it is interesting to note that journalists do not always trust university press releases, as they have been known to exaggerate the impact of a study, due to their reliance on publicity to obtain further funding.
The terminology you use is extremely important, as words can have different meanings in different disciplines. For example the word ‘significance’ to a scientist means that the p-value obtained from a statistical analysis is small enough that the null hypothesis can be rejected. For example a treatment is shown to significantly reduce cell death in comparison to administering water, the null hypothesis in this case would be that the treatment does not affect cell death. But to the general public or a journalist, significance means something that is important and worthy of attention. So to relay your message, it is important to use simpler and understandable terms, and speak in the journalist’s language. This does not necessarily mean dumbing down the science; you just need to disseminate the core message. You cannot expect the public as non-scientists to understand all of the hard-core science.
So there is plenty a scientist can do to help the media report science accurately. But as a member of the public, what can you actually believe? If you see an advertisement or news story and you are not quite sure if there is any evidence to back it up, there is something you can do about it – ask for evidence! Sense About Science has launched a brand new website: www.askforevidence.org, which gives guidance on how you can ask for evidence. You can directly email the company/journalist/publication and request to see evidence behind the claim, or you can fill in a form on the Ask For Evidence website. Companies have already been forced to withdraw products or advertisements, and change policies as a result of being asked for evidence they could not provide to support their claims. Sense About Science also regularly teams up with scientists in the Voice of Young Science network to examine the evidence behind suspicious claims, for example the use of homeopathy in developing countries, and the promotion of detox diets and products. You can see more about their campaigns here: http://www.senseaboutscience.org/pages/voys-campaigns-64.html. So put your critical thinking hat on and ask for evidence the next time you see something a little dodgy. The more people ask for evidence, the more people will expect to be asked, thus we can create a huge culture change.
 Book by Ben Goldacre (2009) Bad Science, Harper Perennial, UK.
A pandemic is sweeping the globe and has transpired into the world’s biggest killer. (And no it is not Ebola, however deadly it is proving to be.) They are killing millions every year. They are non-communicable diseases or NCDs; the five most common being cardiovascular disease, diabetes, cancer, chronic respiratory diseases and mental illness. While many are afraid that the Ebola epidemic will escalate by rapid transmission between individuals, NCDs are far more destructive despite not being transmissible, killing 35 million people worldwide annually; that is 60% of total global deaths.
Many would stereotype the typical NCD patient as being an old, overweight lazy male in the Western world. The reality is very different, 80% of global NCD deaths occur in low- and middle- income countries, and 8 million of these people die below the age of 60. NCDs are fast becoming indicative of poverty, and a major burden on global health and development. So as young people who are passionate about tackling NCDs, is there anything we can do to stem the tide? Thankfully there is, and the NCDFREE bootcamp held in London a couple of weeks ago aimed to equip young people with the skills to make that change.
We began with Prof. Richard Smith who asked if slavery can be abolished, why can’t NCDs? A strong social movement, like the abolitionists or the civil rights movement, is required. An element of outrage needs to be instilled in the public for meaningful change, resembling the outrage observed in relation to AIDS in the 1980s and climate change today. A multi-disciplinary team with a variety of skills to offer can produce a powerful movement and relay the message to lay people. Katie Dain of the NCD Alliance described the prevalence of facilities to support patients of infectious diseases in the developing world, but scarce support exists for NCD patients. She mentioned one diabetes patient who stated that he would rather have HIV, due to the lack of support he receives to manage his diabetes. Dain concluded that we in the Western world created this problem through globalisation and allowing the food industry to run riot. Now it’s time for us to solve it. Futerra co-founder, Ed Gillespie described the bystander effect – people hope someone else will solve the problem. Gillespie said we must understand that solving one problem can create another, but it is still a sign of progress we must persevere with.
Jo Creed from the Jamie Oliver Food Foundation gave us a whirlwind tour of good and bad campaigns, ranging from personalised Coca Cola bottles to the no make-up selfie and the ice bucket challenge. A clear, simple and positive message proves most effective but the educational content is extremely important, as often people become involved in campaigns to gain attention rather than heeding the message. For example many who participated in the recent ice bucket challenge failed to either raise awareness of the rare neurodegenerative disorder amytrophic lateral sclerosis (ALS) or donate to the charity running the campaign. Dan Lewis-Toakley of the petition website Avaaz, emphasised the need to involve everyone to maximise a campaign’s impact. We must make use of powerful statistics but also use human stories; showing your own vulnerabilities can trigger emotional responses from your audience.
Dr Corinna Hawkes from the World Cancer Research Fund gave a fascinating talk on how hidden political interests can often hinder progress in public health affairs. Once a high level UN meeting involved a heated debate on salted anchovies! It emerged that Nordic and Mediterranean countries were competing to promote their diets as being the ‘healthiest’ to increase business for their food products. To overcome this issue we must learn what political interests are at play, leverage them to our own interests, and learn to communicate with politicians or economists in their language, not in scientific terms they will not understand.
We had an insight into social innovation from Dr Harpreet Sood, a Senior Fellow at NHS England, and Dr Fred Hersch, a Clinical Research Fellow at the George Institute for Global Health, Oxford. It is vital to have a strong multi-disciplinary team working on a specific aim within a reasonable time frame. But you will not know if your invention will be effective until you go out and test your prototype, so be open-minded and prepared to improve your product.
The most moving account of the weekend came from filmmaker Batsheva Lazarus. She described how telling an individual’s story is often more persuasive than presenting a plethora of facts. As a scientist this was really eye-opening, we are trained to support every claim with experimental evidence, yet if you want to relay your message to the public or policymakers, they will simply get bored of listening to you. Introducing an emotional component by telling the story of someone who may be suffering from cancer in a low income country for example, can really help your message hit home. This is perhaps the magic behind the short advocacy films created by NCDFREE in Mongolia and Ghana, which have been shown to the WHO and included in global health courses.
The final talk was from NCDFREE founder Dr Alessandro Demaio, a Global Health Fellow at Harvard Medical School, who spoke about his experiences as a leader. To be a successful leader of a movement like NCDFREE, you must truly believe in your idea and speak about it passionately. Having a multi-disciplinary team is helpful with a clear and shared vision. Remain positive in spite of the challenges you face, focus on finding solutions not the problems, provide support to your teammates to continue achieving and keep evaluating your own performance.
Also featured in the bootcamp was a quiz to test our knowledge on NCDs, during which we learnt Halle Berry and Tom Hanks are among those suffering from diabetes! We were trained to relax and control our emotions with a session of yoga and meditation. And we participated in a group challenge to design a campaign and a 60 second film concept answering a real challenge facing the NCD community; the winning pitch will be made into an actual campaign film. The challenge facing my team was to devise a campaign involving smartphones to get young people to care about a disease they may not get for another 30 years. And I am delighted to say we came up with the winning pitch! We designed a film concept where a healthy and unhealthy person were using their smartphones to chat with their ‘future self’ 30 years ahead, and thus saw the consequences of their lifestyles on their health. We concluded the pitch encouraging viewers to join the #ticktock campaign (emphasising that their time is running out if they don’t improve their health) and share their healthy actions on social media. Check out the video of our winning pitch here: http://www.youtube.com/watch?v=ORe9_6ZZ1AM and if this becomes the next viral campaign, remember you heard it here first!
In the meantime NCDFREE has launched #theface of NCDs campaign encouraging people to share their stories of how NCDs have affected their lives, whether it’s affecting their own health or those they love, or observing the impact on local communities and work environments. Do you have an NCD story you would like to share? If so visit http://www.thefaceofncds.org, share your story and help change the face of NCDs.
This piece was originally published on Imperial College's Global Health blog Cafe Communique. It can be viewed here: http://cafecommunique.org/component/easyblog/?view=entry&id=58&Itemid=290
Just six weeks before his death in 2008, American TV journalist Tim Russert underwent a cardiac stress test, as he was already known to have coronary artery disease. He exercised on a treadmill while his blood pressure and heart were monitored. Despite being overweight, hypertensive and having excess cholesterol, which were controlled by medication and lifestyle changes, Russert did not display any symptoms suggestive of imminent cardiac problems. Yet within two months, he died of a sudden cardiac arrest.
How did doctors miss this impending cardiac event? It seems that the body’s defence mechanisms eluded existing medical technology. As you may have read before (Blog post: Blocked Pipework in Our Hearts), our arteries detect that a growing atherosclerotic plaque can reduce blood flow to the intended tissues, so the artery wall expands outwards in an attempt to maintain the diameter of the artery through which blood flows. This process is referred to as positive remodelling or ‘Glagov remodelling’, named after the late Professor Seymour Glagov who demonstrated this phenomenon. Standard angiography – where a dye is administered into the patient’s coronary arteries and X-ray imaging is used to visualise arterial blood flow – will only reveal significant blockages or narrowing of arteries. But if an artery has remodelled considerably to maintain blood flow, atherosclerotic plaques will not be detected in spite of how large they may be. In fact, up to 75% of ruptured atherosclerotic plaques, which have significantly reduced or blocked blood flow, exhibit positive remodelling .
Once the plaque reaches the ‘Glagovian’ limit of blocking 40% of the cross-sectional area of the artery, expansion can no longer occur so further plaque growth only serves to block blood flow, otherwise referred to as negative remodelling . This is when arterial disease will be detected by angiography. As described previously, smooth muscle cells from the artery wall move into the developing plaque and create a layer on top full of smooth muscle cells and collagen produced by these cells, called the fibrous cap. When this cap becomes extremely thin and weak, due to proteins produced by macrophages (the main inflammatory cell) breaking it down, the cap ruptures and can trigger the appearance of a blood clot. If a blood clot does not appear, the ruptured cap will heal itself with the further production of collagen from the smooth muscle cells. The plaque may undergo several cycles of rupture and repair without any blood clots and subsequent symptoms appearing. And it is this process that determines the speed at which the transition from positive to negative remodelling occurs. If the plaque is permitted to grow with the gradual intrusion of lipids and inflammatory cells, the transition may take decades. However repeating cycles of rupture and repair will rapidly increase the rate at which the plaque grows, thus a seemingly harmless plaque can suddenly present a major threat within months or even weeks. This chain of events was most likely responsible for the sudden and unforeseen demise of Tim Russert.
So is there any hope of detecting these rapidly developing plaques before it is too late? Thanks to scientists like Professor Jagat Narula (whose recent lecture at Imperial College is the inspiration behind this blog post), there is now technology available to detect these invisible killers. Optical coherence tomography (OCT) imaging utilising near-infrared light, can be used to detect fibrous caps that are thinner than 65μm (μm = microns or micrometres, one thousandth of a millimetre), which are at high risk of rupturing. Computed tomography (CT) angiograms - where an iodine-rich dye is injected into the patient and then a CT scan of the blood vessels is performed – can be used to observe the necrotic core of plaques (full of dead or dying macrophages and lipids), which is linked to extensive remodelling of the artery, and the presence of calcium deposits in plaques; also indicative of an increased risk of clinical events . This is an extremely important development as a higher degree of remodelling and larger necrotic cores are associated with an earlier onset of acute cardiovascular events.
Top: CT image where two plaque are pointed out. The left-hand arrow shows a large plaque, right-hand arrow shows a calcified plaque (calcification in white). Bottom: Angiogram where blood flow appears in grey. Left-hand arrow shows the large plaque in the above image but blood flow is unaffected. Right-hand arrow shows blocked blood flow due to the calcified plaque. Images from Hoffmann et al, (2006) Coronary CT Angiography, J Nucl Med, 47(5): 797-806.
It now appears that a combination of CT angiography, positron emission tomography (PET) and the use of FDG (if you really want to know what it stands for, it’s 2-fluorodeoxyglucose) as a contrast agent can be used to visualise plaques with a high level of macrophage-based inflammation . As inflammatory cells have a high rate of metabolism, consuming larger amounts of glucose than other cells to generate energy for their demanding inflammatory activities, FDG acts like glucose and is taken up by these macrophages. And as the FDG is labelled with fluorine-18, a radioisotope emitting positrons as it decays, the PET scanner detects these positrons being emitted at a high rate within the plaque macrophages. Mannose is another sugar taken up by macrophages, and macrophages with the mannose receptor on their cell surface are more prevalent in high-risk plaques. Subsequently fluorine-18 labelled FDM (2-fluorodeoxymannose) has also been successfully used to image macrophage-based inflammation in atherosclerotic plaques . In fact, macrophages take up a greater amount of FDM than FDG, especially when they are starved of oxygen (a condition called hypoxia) in the plaque, which has no direct blood supply until small leaky blood vessels grow into it later on. Thus FDM maybe a better option to image inflammatory plaques. While there is still work to do to improve the quality of these imaging methods and ease the discomfort for patients during the procedure, it is only matter of time until we can identify these dangerous high-risk plaques before it is too late.
Atherosclerosis is broadly considered a disease of modern times caused by processed and fatty foods, low levels of exercise or old age. While these causes may apply to today’s patients, it is not a disease exclusive to current generations. CT scans of Egyptian, Peruvian, Native American and Russian mummies have detected calcified atherosclerosis in coronary arteries supplying blood to the heart, and carotid arteries supplying blood to the head, as is commonly seen in patients today . But how could they possibly get atherosclerosis when their diets and lifestyles were completely different? Further examination of the mummies showed these individuals had black lungs, much like smokers of today. Thousands of years ago people relied on wood- or coal-fuelled fire for warmth and cooking, and were thus highly exposed to smoke and soot. Infectious diseases were also more prevalent, and high levels of chronic inflammation caused by infections are known to increase atherosclerosis. So as is commonly advised, don’t eat junk and don’t smoke. Not only will it keep your arteries clean, but do you really want to be the smelliest person on the train? I certainly won’t sit next to you….
1. Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, Malik S, Fuster V, Finn A V., Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques., J. Am. Coll. Cardiol. 61 (10) (2013), 1041–51.
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The majority of residents in England have benefited from free healthcare provided by the National Health Service (NHS). I think it is fair to say that the majority of us would be in a worse state of health or even not living if it wasn't for the NHS. The UK economy benefits by million of pounds every year as a result of the NHS keeping the British workforce healthy. According to the latest research, every £1 invested in public healthcare increases GDP by £3 . Yet the government insists on cutting funding for the NHS, while it spends billions of taxpayers' money bailing out corrupt banks, maintaining the monarchy's lavish lifestyle, and fuelling futile wars overseas. Where is the sense in that?
I know how the NHS has helped me. I was born in an NHS hospital with no complications for me or my mother. As a baby my elbow was dislocated, and an NHS doctor popped it back in place. As a toddler I was hospitalised due to severe asthma, which thanks to the NHS is no longer a problem for me. My father was treated for a heart attack and had life-saving heart bypass surgery. Incredibly 10 years on, he is in excellent health. I have no idea how we could have possibly afforded to pay for his open heart surgery had the NHS not existed. And now I have the privilege of working with NHS doctors and scientists to hopefully find the next treatment for heart disease. Of course there are sometimes blunders, nothing is perfect but some healthcare is better than none at all. And the overwhelming majority of healthcare provided by the NHS is of the highest standard, arguably the best in the developed world .
If you have been relying on the BBC for your news, you will have no idea that we now face the possibility of no longer having access to free healthcare by the next general election, and blunders could become the norm with a privatised health service, prioritising profit over welfare. People from countries all over the world envy our national health service and yet our government is destroying it before our very eyes, just to gain lucrative business deals from their pals. If we don't act now, our NHS will disappear and we could pay with our lives, literally. After all good health is not a privilege, it is a human right. So think to yourself, how has the NHS helped you and could you live without it?
Act now! Please join the ongoing People's March for the NHS, which will conclude with a rally in Trafalgar Square at 3.30pm on Saturday 6th September. Please visit 999callfornhs.org.uk for more details and sign up for the march!
Re-organising the world's largest public health service could not only damage healthcare provision but also medical innovation
In March 2012, the Conservative and Liberal Democrat coalition government (also cynically known as the Con-Demned coalition) passed the Health and Social Care Act through parliament. The Act permits radical re-organisation of England’s world-renowned National Health Service (NHS). The scale of re-organisation, perhaps a misnomer for extensive privatisation, has raised serious concerns about the level of healthcare that will remain freely available to taxpayers. One concern that has not been discussed in great detail is how NHS privatisation will affect the future of medicine i.e. training future doctors and advancing medical innovation.
The Labour party founded the NHS in 1948, pledging to deliver high quality healthcare to all citizens regardless of wealth, and funded entirely by taxpayers . The NHS has since expanded into the largest publicly funded health service in the world featuring world-renowned hospitals, and allowing patients to benefit from various health services they could not otherwise afford, ranging from dentists to open-heart surgery. As a result, the NHS is most beloved in the UK with consistently high levels of satisfaction expressed by patients. The majority of today’s population was born with the aid of NHS services, and many rely on state-funded healthcare during their lifetime. The UK’s life expectancy has also continued to rise since the NHS was founded. The UK was recently rated as having the best health service amongst 12 developed countries, including the US, Australia and Germany . A vibrant health organisation placing skilled health professionals and scientists under one roof has fostered numerous medical discoveries, revolutionising healthcare not only within the NHS, but throughout the world. Examples include: the link between smoking and lung cancer, the UK’s first ever heart transplant, and the world’s first ‘test tube’ baby born as a result of in vitro fertilisation (IVF) .
So how will the re-organisation permitted by the Health and Social Act affect the ability of the NHS to deliver medical innovation? Squeezing of the NHS budget and increasing staff workloads in recent years already prompted a large migration of doctors to countries like Australia, in the hunt for reasonable salaries and a more manageable work-life balance. The loss of such valuable talent has harmed medical training and clinical research in the NHS. The transfer of services and facilities from the state to the private sector inevitably means profit is valued more than patient welfare. As a result we have already witnessed a multitude of hospital closures and staff redundancies, and this will aggravate existing problems. Unite the Union argues that the private sector may ‘cherry-pick’ more profitable services and surgical procedures causing a loss of low-demand but still vital services for some patients, and further opportunities to train junior doctors and medical students .
Most hospitals collaborate with academic research laboratories providing patient samples for research experiments. Hospital mergers and closures will drastically cut the number of collaborations and the pool of samples available for such research, thus limiting the rate at which progress can be made towards the next medical therapy. The private sector may even decide to charge for medical training and access to patient samples and clinical research facilities, elevating costs for medical students and researchers (generally funded by the taxpayer or charities) respectively.
On the contrary, the government states that the private sector will play a greater role in medical research through an increase in academic-industry collaborations . Such a move would be advantageous in obtaining funding for medical research, as private companies tend to offer more funding than research councils and charities. But naturally private investors will expect something in return. We are well aware that pharmaceutical companies have failed to invest in research on diseases plaguing developing counties, due to the lack of financial return . Pharmaceutical companies often spend millions of pounds investing in the development of one drug, aiming to earn the money back from sales of the drug, which developing states cannot afford to pay for. Hence a similar trend could occur in the UK, where pharmaceutical and medical device companies may refuse to invest in research to develop treatments for rare diseases due to low prospects in profiting, or they may develop treatments but charge colossal amounts unaffordable for patients. With strengthening of academic-industry collaborations also comes the probability that more state and charity funding of academic research will result in discoveries that subsequently rely on industry to produce the treatment, and ultimately reap the profits.
Of course these possibilities are hypothetical, but we have already seen evidence both within the NHS and in other scenarios that these negative consequences are unfolding and could severely jeopardise standards of healthcare delivery and the future of medical innovation, not only in the UK but worldwide. Are these consequences we want to live with? And in case you are wondering what is motivating this large-scale privatisation of the NHS, take a look at this: http://socialinvestigations.blogspot.co.uk/2012/02/nhs-privatisation-compilation-of.html
Please join the People's March for the NHS, further details here: http://999callfornhs.org.uk
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 Book by Ben Goldacre (2012) Bad Pharma: How Medicine is Broken, and How We Can Fix It, Fourth Estate, UK.
Dr. Anusha Seneviratne
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