- Nonadherence to medication is a vast and rapidly growing killer epidemic
- The epidemic is under reported, under-treated and costs healthcare systems billions
- No healthcare stakeholder has assumed responsibility for reducing the burden of nonadherence and so it has become an orphan issue
- Psychological techniques used by policy makers have been shown to change peoples’ behaviours, improve healthcare and reduce costs
- The proliferation of smartphones embedded with behavioural techniques designed to coax people to adhere to medications holds promise
- But recent research suggests that thousands of apps devised to reduce nonadherence use behavioural techniques sub-optimally
- There is an opportunity to significantly improve nonadherence to medication by optimally utilising behavioural techniques and digital technology
- The challenge needs to be embraced by all healthcare stakeholders
Nonadherence to prescribed medication for patients with chronic long-term conditions (LTCs) is an out-of-control epidemic, which is undetected and undertreated. It kills hundreds of thousands, erodes the life chances of millions, costs billions and is one of the biggest obstacles to effective healthcare in the 21st century. According to the World Health Organization (WHO), “increasing the effectiveness of adherence interventions may have far greater impact on the health of the population than any improvement in specific medical treatments”.
There are a number of reasons why people with LTCs stop taking their medication, which include: (i) fear of potential side-effects, (ii) lack of understanding because taking a medication every day to reduce the risk of something bad happening can be confusing, (iii) failure to see immediate improvement, (iv) too many medications that often cannot be taken at the same time, (v) patients who are depressed are less likely to take their medications as prescribed, (vi) concerns about becoming dependent on a medicine and (vii) high drug costs, particularly in the US.
No healthcare stakeholder - patients, doctors, carers, regulators, pharmacists, pharmaceutical companies and healthcare providers – has made nonadherence a priority, so it has become an orphan issue. We suggest that all health stakeholders have a role to play in nonadherence and would benefit by employing psychological techniques designed to encourage people to change their behaviour.
Because nonadherence to medication has a significant prevalence in people living with LTCs, we begin this Commentary by describing the vast and rapid growth of LTCs and their associated eyewatering costs. The management of LTCs rests with primary care doctors, but the average doctor-patient consultation is just a few minutes and more importantly, the majority of patients do not remember most of the information provided in such consultations. Not only do primary care doctors have little time to prescribe and explain medication regimes, there is little incentive for them to address nonadherence. We raise the question of whether doctors might be part of the problem by citing a seminal paper published in The Lancet in 1974, which suggests that doctors have a propensity to medicalise healthcare and over-prescribe medicines. This can transform reasonably healthy people into habitual patients. We then describe a trend gaining momentum both in the US and the UK, whereby community-based pharmacists are becoming a healthcare destination and are well positioned to play a significant role in denting the nonadherence epidemic. We draw passing reference to pharmaceutical companies’ interest in reducing nonadherence. We conclude by describing a number of research studies, which examine the confluence of mobile telephony and advances in behavioural science, which facilitate the increased use of apps embedded with behavioural techniques to address nonadherence to prescribed medication. Despite the large and growing use of such apps, studies suggest that the use of behavioural techniques in mobile applications to address nonadherence is sub-optimal. Thus, there remains an opportunity for using advances in behavioural theory and practice to promote sustained and significant lifestyle behaviour changes designed to reduce the nonadherence to prescribed medication epidemic.
In the UK nonadherence to prescribed medication among people with LTCs has a similar impact. According to a 2014 UK House of Common’s Health Committee report, “Effectively managing LTCs is widely recognised to be one of the greatest challenges facing the 21st-century”. Seventy percent of total expenditure on healthcare in England is associated with the treatment of the 30% of the population with one LTC or more, and the number of people in England with one or more such condition - currently 15m - is projected to increase to around 18m by 2025. Care for LTCs presently accounts for 55% of primary care doctors’ appointments, 68% of outpatient and A&E appointments and 77% of inpatient bed days. The cost to NHS England of people with LTCs not taking their prescribed medicines appropriately and thereby not getting the full benefits to their health is estimated at more than £500m (US$635) a year, with a further cost of £300m (US$381) on wasted medication.
Despite the fact that a medical consultation is a complex and multidimensional process, which is pivotal to the health of patients, the average time spent for each consultation is short and there is little or no time for doctors to educate or motivate patients. A 2017 paper published in the British Medical Journal (BMJ) reviewed 28.6m doctor-patient consultations across 67 countries and found that, in 18 countries, which represented about 50% of the global population, on average a doctor-patient consultation is five minutes or less. On average, British patients spend just over nine minutes with their primary care doctor during an appointment and in the US, it is 17 minutes. More significantly, a 2016 study published in Health Expectations, suggested that patients only remember about a fifth of the information discussed in a standard doctor-patient consultation.
- The CoVID-19 pandemic created an unprecedented global shock and killed hundreds of thousands
- Nations responded by closing their borders, implementing stringent lockdowns and saying the world is at war with a common invisible adversary
- Responses to the outbreak diverged in the different regions of the world
- Asian countries responded rapidly and effectively
- The US and UK responded slowly and ineffectively
- Observers suggested that the divergent responses to CoVID-19 signal a shift in power and influence from West to East
- National responses alone are insufficient to effectively deal with the coronavirus
- Only by embracing effective international cooperation will governments protect their citizens and safely exit the CoVID-19 crisis
National leaders have described the coronavirus CoVID-19 pandemic as “the enemy”. In attempts to protect their citizens, nations turned inwards and closed their borders, implemented stringent lockdown restrictions and suggested that the world is at war with a common adversary it cannot see. The speed and effectiveness of national responses to the new coronavirus crisis differed, but not even the wealthiest, most advanced nations were able to protect their citizens. The global coronavirus crisis made millions seriously ill, killed hundreds of thousands, destroyed industries, bankrupted thousands of companies, caused economies to nose-dive and threw societies into turmoil. Only by avoiding nationalist policies and embracing effective international cooperation will governments protect their citizens and safely exit the CoVID-19 crisis.
CoVID-19 has rapidly spread throughout the world with a scale and a severity not witnessed since the devastating Spanish Flu in 1918. So-called because Spain was neutral during WW1 and was one of the few countries where journalists were free to report on the outbreak. In an era before antibiotics and vaccines, the Spanish Flu claimed the lives of nearly 0.68m Americans, 0.25m Britons and between 50 to 100m people worldwide. Adjusting for population growth, that is equivalent to between 200 and 425m today.
At the time of writing - June 2020 - neither an adequate therapy nor a vaccine has been developed and CoVID-19 remains prevalent in populations throughout the world. Even with today’s scientific advances, infectious diseases are notoriously challenging to either treat or cure: an Ebola vaccine was more than two decades in the making; despite the first cases of the human immunodeficiency virus (HIV) presenting in 1983, we still do not have a therapeutic preventative vaccine for the disease; nor do we have a vaccine for severe acute respiratory syndrome (SARS), a killer coronavirus, which also originated in China and was unknown before its outbreak in 2002.
Notwithstanding, governments have lifted lockdown restrictions in order to get their economies working again. V, U, W and L are letters of the alphabet used to describe the shape of a recovery following the economic crisis caused by CoVID-19. Stringent lockdowns forced economies into unprecedented cold storage, and no one knows what shape a recovery will take since professional forecasters have never encountered anything like the sheer magnitude of the current economic crisis.
The Bank of England’s Monetary Policy Report published in May 2020, warned that the coronavirus has caused the worst economic crisis in 300 years. So, emerging from this is unlikely to be either straightforward or quick. National responses to the coronavirus outbreak were mixed. Although it is too soon to know the longer-term effects of the virus, China, Singapore and South Korea are among the countries that responded early and effectively, while the US and UK, together with other Western European countries, responded late and less effectively. As of June 1, China, with a population of 1.4bn, had 83,017 confirmed cases and 4,634 deaths; South Korea with a population of 52m, had 11,537 cases and 270 deaths, and Singapore with a population of 5.7m, had 34,884 confirmed cases and 23 deaths.
This Commentary describes the divergent national responses to the CoVID-19 pandemic; in particular that of China, Singapore, South Korea, the US and UK. China’s more effective response might have been because Beijing benefitted from the lessons it learned after the SARS epidemic in 2002. Governments also differed in their approaches to lifting restrictions. China’s approach was slower than that of the US and more determined to make some of the unexpected benefits thrown up by the crisis permanent. Some observers perceive such variances as a difference between liberal and illiberal nations. Others view the divergences as a shift in power and influence from West to East. We suggest that the divergent responses and outcomes are a product of the capacity and legal authority of different states and reveal different mindsets and competing views about solutions. We also contend that the devastation created by the pandemic will only be resolved with effective international cooperation. However, it is difficult to see this happening in the near term as the pandemic has become a theatre for a wider political disagreement between the US and China, in which other nation states are being forced to take sides.
China, Singapore and South Korea leveraged the collectivists mindset of their citizens, their centralised authority and digital infrastructures to quickly implement the gold standard “test-trace-and-isolate” strategy to reduce and control the virus. The reason for such prompt actions and the subsequent relatively low number of cases and deaths in these Asian countries is described by Byung-Chul Han, a South Korean-born German Professor of Philosophy at the Universität der Künste in Berlin. In an article published on May 22, in the Spanish newspaper El Pais, Han suggests that Asian nations won the battle against the CoVID-19 outbreak because their citizens, “have a collectivists mindset, which comes from their cultural tradition of Confucianism. Asians are less rebellious and more obedient than people in the West. They trust the state more. Daily life is much more organised, and Asians are strongly committed to digital surveillance. The epidemics in Asia are fought not only by virologists and epidemiologists but also by computer scientists and big data specialists”.
Given Iran’s response to CoVID-19 has been less effective, it seems reasonable to suggest that the Confucian mindset, rather than authoritarianism, appears to provide at least a short-term advantage. In early March, at the Shia Muslim Masumeh shrine in the holy city of Qom, pilgrims licked and kissed its gates. Qom experienced Iran’s first outbreak of the coronavirus and became the country's worst-hit city. Shortly afterwards the government closed all major Shia shrines across the Islamic republic and reopened them again in late May. As of June 1, Iran with a population of 81m, had confirmed 154,000 cases of CoVID-19 and 7,878 deaths.
During these unprecedented challenging times caused by the coronavirus CoVID-19 pandemic, we trust that you all stay safe and well and let the spirit of Ramadan remain in your hearts and light up your souls from within.
To everyone working long and stressful hours on the frontline of healthcare; thank you for the sacrifices you’re making every day to help others in their moments of need. Your dedication, commitment and courage have our deepest gratitude and admiration.
Also, our heartfelt thanks go to all key workers who are unselfishly providing essential services, which are helping all of us through this coronavirus outbreak. Your resolution and mettle make a huge difference to our daily lives and we hold you in the highest esteem.
#coronavirus #CoVID-19 #frontlinehealthcareworkers #keyworkers #healthcare
- The coronavirus CoVID-19 has created the greatest health-cum-economic-cum-societal crisis in history and put unprecedented pressure on overstretched and unprepared healthcare systems
- Before the coronavirus outbreak, primary care in England already was in crisis, fuelled by an aging population, a large and increasing demand for its services and a shrinking supply of health professionals
- In 2019, before the outbreak, 75% of primary care doctors (GPs) across 540 clinics in England were over the age of 55 and nearing retirement and a large percentage of newly trained GPs were seeking employment abroad
- Patients who could not get GP appointments used A&E departments as convenient drop-in clinics for minor ailments, which significantly increased healthcare costs and burden
- For decades successive UK governments have tried in vain to transform the nation’s primary care services predicated upon face-to-face patient-doctor consultations
- Several well-funded long-term national plans advocated increased digitization of some routine primary care services
- But before the coronavirus outbreak only 1% of all primary care consultations were online
- What these national plans could not achieve in decades appears to have been achieved in days by the UK’s NHS’s response to the coronavirus outbreak
- Today, millions of patients in England are having face-to-face appointments with their GPs replaced by telephone or video consultations
- Could CoVID-19 transform the UK’s traditional primary care model?
The coronavirus CoVID-19
The 1918 Spanish Influenza remains the most devastating virus in modern history. The disease swept around the globe and is estimated to have caused between 50m and 100m deaths. A cousin of the same virus was also behind the 2009 swine flu outbreak, thought to have killed as many as 0.58m. Other major viral outbreaks include the Asian flu in 1957, which led to roughly 2m deaths and the Hong Kong flu, which killed 1m people 11 years later.
In this Commentary
UK’s primary care crisis
Changing and aging population
Shrinking supply of GPs
Failing national initiatives to improve primary care
The UK’s NHS
National plans to improve the NHS
NHS long term plans and private online healthcare solution companies have delivered little change
The plan emphasises the importance of developing digital services, and recommends that within five years, all patients should be able to access GP consultations via a telephone or online. This goal is supported by NHS Digital, which is the national information and technology partner to the UK’s health and social care system. Its mission is to harness the power of information and technology to improve healthcare. Over the past decade there has been an increasing number of innovative online private healthcare solutions companies entering the market. (see below). Notwithstanding, these and the NHS’s well-funded national plans, have failed to dent the primary care crisis by slowing the vast and escalating demand for healthcare and reversing the shrinking supply of healthcare professionals. So, for the past two decades at least, the NHS has tended to operate on the cusp of a crisis.
A doctor only needs to touch a patient if s/he is going to operate on that patient
Innovative online healthcare solution enterprises
Technologically heavy and strategically light
A Chinese example
- The burden of breast cancer throughout the world is significant and increasing
- Research has shown that a cheap pill (anastrozole) halves postmenopausal women’s risk of breast cancer and continues to be effective seven years after women stop taking the drug
- Anastrozole has less side-effects and is more effective than comparable treatments
- Government watchdogs both in the UK and US recommend anastrozole
- But the uptake of the drug in the UK is relatively low
- Doctors are not prescribing anastrozole and women are not availing themselves of the drug
- The UK’s NHS should employ new behavioural techniques to influence and change doctors’ and patients’ decisions and increase the uptake of anastrozole to reduce the burden of breast cancer
Will behavioural techniques improve breast cancer outcomes?
Research findings reported in the December 2019 edition of The Lancet and also presented at the December 2019 San Antonio Breast Cancer Symposium in Texas, show that a cheap pill, anastrozole, if taken once a day for 5 years, not only halves postmenopausal women’s risk of breast cancer, but continues to be effective seven years after stopping treatment, which for the first time, suggests a long-term benefit.
- Bioengineers throughout the world are competing to achieve the Holy Grail: an affordable, point-of-care blood test - liquid biopsy - that detects cancer before any symptoms present
- Success in achieving this will save millions of lives, substantially reduce healthcare costs and make investors, researchers and organisations billions
- Despite significant advances no one has yet achieved the Holy Grail and there remains a substantial gap between researchers’ aspirations and reality
- How close are we?
Alfattani was presenting research findings of a small study at the National Cancer Research Institute’s (NCRI) conference in Glasgow, Scotland, in November 2019, which is an international forum for showcasing cancer advances.
A September 2019 HealthPad Commentary described another early detection test for breast cancer called CanRisk, which has been developed by researchers from Cambridge University’s Centre for Cancer Genetic Epidemiology and has the potential to identify women with different levels of risk of breast cancer.
Alfattani and bioengineers from the universities of Nottingham and Cambridge are players in a vast and rapidly evolving international army of researchers engaged in an intensely competitive global race to develop an affordable, point-of-care, early detection test (EDT) for cancer based upon a liquid biopsy and next generation sequencing technologies. The Holy Grail is for such a test to detect cancer cells in an asymptomatic patient, locate the tissue of origin and give that person an early diagnosis when treatment is more likely to be successful; and to do all this with 100% accuracy.
Although Alfattani’s research study is modest, her findings are potentially clinically relevant because they are on the Holy Grail therapeutic pathway, and her preliminary findings suggest that a simple, cheap and easy-to-use blood test - liquid biopsy - could detect breast cancer five years before any symptoms present. If demonstrated to be exquisitely accurate, safe and efficient by a larger study, which already is underway at Nottingham University’s CEAC, Alfattani’s research could be a key to saving thousands of lives and substantial amounts of money.
Gold standard breast cancer screening
In this Commentary
Partial epidemiology of breast cancer
The Nottingham researchers took blood samples from 90 breast cancer patients at the time they were diagnosed with the disease and matched them with samples taken from 90 patients without breast cancer (the control group). Researchers employed technology (protein microarray), which allowed them to screen the blood samples for the presence of autoantibodies against 40 TAAs associated with breast cancer and also 27 TAAs not known to be linked with the disease. The accuracy of the test improved in the panels that contained more TAAs.
A panel of five TAAs correctly detected breast cancer in 29% of the samples from the cancer patients and correctly identified 84% of the control group as being cancer-free. A panel of seven TAAs was able to detect disease in 35% of cases with breast cancer and rule out 79% of patients in the control group. The most successful technique was a panel of nine antigens, which correctly identified the disease in 37% of cancer samples and no cancer in 79% of the controls. “The results of our study showed that breast cancer does induce autoantibodies against panels of specific tumour-associated antigens. . . . . The results are encouraging and indicate that it is possible to detect a signal for early breast cancer. Once we have improved the accuracy of the test, then it opens the possibility of using a simple blood test to improve early detection of the disease”, said Alfattani.
David Crosby, head of early detection at the Cancer Research UK charity, said, “Diagnosing cancer at the earliest stages before it grows or spreads gives patients the best chance that their treatment will be successful. So, the potential to detect markers in the blood before other signs appear is promising”.
- Prime editing devised by researchers at the Broad Institute led by David Liu is a significant advance of the original CRISPR gene editing tool discovered in 2012
- CRISPR can cut and edit your DNA to correct defects inside your body’s cells to prevent and heal a range of incurable diseases and has revolutionized biomedicine
- The original CRISPR is fraught with inaccuracies referred to as off target effects
- Prime editing substantially reduces CRISPR’s off target effects and has the potential to correct up to 89% of known disease-causing genetic variations
- CRISPR also has the capacity to edit genes in an embryo in such a way that the change is heritable
- In 2018 Chinese researcher He Jiankui “created” the world’s first CRISPR babies
- This triggered international criticism from scientists and bioethicists
- A principal concern is that CRISPR is easy-to-use, cheap, regularly used in thousands of laboratories throughout the world and there is no internationally agreed and enforceable regulatory framework for its use
In 2012 the world of biomedicine changed when a revolutionary gene editing technology known as CRISPR-Cas9 (an acronym for Clustered Regularly Interspaced Short Palindromic Repeats) was discovered. The technology harnesses your body’s naturally occurring immune system that bacteria use to fight-off viruses and has the potential to forever change the fundamental nature of humanity. Since its discovery CRISPR has been developing at lightning speed primarily because it is simple and affordable and today is used in thousands of laboratories throughout the world.
We also review a case where an ambitious scientist “created” the first CRISPR babies. This immediately triggered international criticism and a call for tighter regulatory control of the technology. Scientists and bioethicists are concerned that CRISPR can easily be used to create heritable DNA changes, which ultimately could lead to ‘designer babies’.
These two accounts of CRISPR might seem “opposites” and not sit well together in a single Commentary. Notwithstanding, what prompted putting them together was John Travis, the News Managing Editor of the well-known scientific journal Science, who soon after CRISPR’s discovery in 2012 said, “For better or worse we all now live in CRISPR’s world”.
CRISPR and your DNA
CRISPR is different to traditional gene therapy, which uses viruses to insert new genes into cells to try and treat diseases and has caused some safety challenges. CRISPR, which avoids the use of viruses, was conceived in 2007 when a yogurt company identified an unexpected defence mechanism that its bacteria used to fight off viruses. Subsequent research made a surprising observation that bacteria could remember viruses. CRISPR has been likened to a pair of microscopic scissors that can cut and edit your DNA to correct defects inside your body’s cells to prevent and heal a range of intractable diseases. The standard picture of DNA is a double helix, which looks similar to a ladder that has been twisted. The steps in this twisted ladder are DNA base pairs. The fundamental building blocks of DNA are the four bases adenine (A), cytosine (C), guanine (G) and thymine (T). They are commonly known by their respective letters, A, C, G and T. Three billion of these letters form the complete manual for building and maintaining your body, but tiny errors can cause disease. For example, a mutation that turned one specific A into a T results in the most common form of sickle cell disease.
The original CRISPR
Subsequently however, the paper was retracted, and an error correction was posted on a scientific website. Contrary to their original findings, the authors of the Nature Biotechnology paper restated that the CRISPR-Cas9 gene editing approach, "can precisely edit the genome at the organismal level and may not introduce numerous, unintended, off-target mutations".
Notwithstanding, researchers remained concerned about CRISPR’s off target effects and several devised a technique, referred to as base editing, to reduce these. Base editing is described in three research papers published in 2017: one in the November edition of the journal ‘Protein and Cell’, another in the October edition of ‘Science’ the and a third by researchers from the Broad Institute, in the October edition of the journal ‘Nature’. Base editing takes the original CRISPR-Cas9 and fuses it to proteins that can make four precise DNA changes: it can change the letters C-to-T, T-to-C, A-to-G and G-to-A. The technique genetically transforms base pairs at a target position in the genome of living cells with more than 50% efficiency and virtually no detectable off-target effects. Despite its success, there remained other types of point mutations that scientists wanted to target for diseases.
- Diabetic foot ulcers (DFUs) are a result of diabetes complications and can lead to amputations and death
- Scientists and clinicians struggle to reduce the vast and escalating burden of DFUs
- In wealthy countries like the UK there are specialist multidisciplinary diabetic foot clinics
- New and innovative therapies are beginning to emerge, which accelerates the rate of complete wound closure for DFUs
- Notwithstanding new products coming to market, the best therapy is prevention
This Commentary discusses diabetic foot ulcers (DFUs) within the context of chronic wounds. Although chronic wounds tend to be an overlooked area of medicine and do not feature prominently in the popular media; NHS England, spends £5bn a year treating 2m patients with chronic wounds. The incidence rates of people affected with wounds are rising fast and some experts suggest that nearly 60% of all wounds become chronic. According to Una Adderley, a wound expert and Director of NHS England’s National Wound Care Strategy Programme, therapy in England for chronic wounds is patchy and suboptimal, “leading to non-healing or delayed healing (which) increases the number of people living with chronic wounds. Too many people are receiving care for which there is little evidence that it works and too few are receiving care for which there is strong evidence that it works”.
According to a 2019 report by the consulting firm MarketsandMarkets the global wound care market in 2019 is estimated to be US$20bn and projected to reach US$25bn by 2024. Market drivers include the vast and fast-growing incidence rates of hard-to-heal chronic wounds, a large proportion of which are associated with diabetes, increasing R&D spending, technological developments, the growing use of regenerative medicine in wound care, recent advances in molecular data that have contributed to genome sequencing, and the increasing use of AI in the management of wound care solutions. The chronic wound care markets of North America and Europe are expected to grow at a CAGR of ~4.5% for the next 5 years, but the highest CAGR is expected in Asia where the vast pool of patients is increasing significantly, and favourable reimbursement policies are expected to persist in the region for the next decade.
When accompanied by an underlying condition such as diabetes, chronic wounds in the form of DFUs, are challenging to heal and have a deleterious effect on your quality of life: you experience pain, suffering, disfigurement, anxiety impaired mobility, malodour and social isolation. Because the prevalence of diabetes is increasing worldwide, DFUs have become a large, severe and growing public health issue as described in two research papers published in 2019.
One, published in the May 2019 edition of Diabetic Medicine, reports findings of an 18 year study of DFUs, and suggests that although current therapies in the UK result in better than previously reported survival in persons < 65 years (10 year survival is 85%), treatments fail to, “reduce recurrent incidence (of DFUs and) cumulative prevalence of all ulcers continues to increase”; from 20.7 to 33.1 per 1,000 persons between 2003 to 2017. The second paper, published in the January-March 2019 edition of the International Journal of Applied Basic Research, report sfindings of a prospective Indian study of 63 patients >18 with DFUs and shows the increase in the severity of DFUs and the consequent increase in the rate of hospital readmissions, amputations and mortality.
Diabetes is a chronic disease that occurs either when your pancreas does not produce enough insulin or when your body cannot effectively use the insulin it produces. Insulin is a hormone that regulates your blood sugar level. High blood sugar levels (hyperglycaemia) is a common effect of uncontrolled diabetes and can lead to serious complications, which include blindness, kidney failure, heart attacks, stroke, diabetic foot ulcers (DFUs), and lower limb amputations. According to the World Health Organization, the global prevalence of diabetes among people >18 has risen from 4.7% in 1980 to 8.5% in 2014. Today, some 422m people worldwide have diabetes, which has increased from 108m in 1980. There is expected to be some 642m people >18 living with diabetes by 2040.
If you have diabetes you are prone to ulcers because your increased blood sugar levels create thick, sticky blood, which can lead to peripheral artery disease (PAD), neuropathy (a loss of sensation due to nerve damage), and/or problems with circulation due to damage to your small blood vessels, which reduce your body’s ability to heal injuries.
Signs and symptoms of DFUs include numbness in your toes and a loss of feeling in your feet, painful tingling sensations, blisters, minor abrasions and cuts without pain that do not heal, skin discoloration and temperature changes With a loss of sensation, a minor injury to your foot can go unnoticed and untreated, and quickly lead to an ulcer. If you are living with diabetes, ulceration is an ongoing challenge. Only about 66% of DFUs eventually heal without surgery. If you have had a foot ulcer you are at increased risk of further ulceration. Studies suggest that around 25% of people living with diabetes who become ulcer-free have developed new ulcers within 3 months, and 34% to 41% within 12 months. Some foot ulcers are painful, and treatment often requires that you spend a significant amount of time visiting clinics to frequently change your wound dressings. The poor prognosis of DFUs is often attributed to other complications of diabetes such as peripheral neuropathy, peripheral vascular disease and persistent hyperglycaemia. Managing diabetic foot ulcers is a major challenge for healthcare systems globally and the main cause of more than half of nontraumatic lower limb amputations: every 30 seconds in the world, a lower limb is amputated due to diabetes. Amputations have life-altering repercussions for patients and represent a significant burden for the healthcare industry as a whole. Between 0.03% and 1.5% of people with DFUs require an amputation and most amputations start with ulcers.
For major amputations, the prognosis is poor because your other limb is at risk. Research suggests that only around 50% of patients survive for two years after major diabetes related amputations. The one-year mortality rate has been estimated at 32.7% after major amputation and 18.3% after minor amputation if you have diabetes. Five-year cumulative mortality for patients with diabetes undergoing a first major amputation has been estimated at 68% to 78.7%. Thus, if you have diabetes and a DFU you have almost a 50% chance of being dead within five years, which is significantly higher than for people with either breast (18%) or prostate (8%) cancers.
In the UK some 70,000 to 90,000 people living with diabetes have DFUs at any one time. If you have diabetes you are about 23 times more likely to experience an amputation than someone without diabetes. In England, diabetes leads to more than 9,000 lower limb amputations each year. Each week in England some 169 people undergo an amputation procedure as a result of diabetes. Analysis by the charity Diabetes UK found that between 2014 and 2017, 26,378 people had lower limb amputations linked to diabetes, which represented a 19% rise from 2010 to 2013. Diabetes affects almost 3.7m people in the UK. In 2017 NHS England launched a special transformation fund aimed at improving patients with diabetes access to specialist multidiscipline foot care clinics to help avoid amputations.
In the video below Hisham Rashid, Consultant Vascular Surgeon at King’s College Hospital, London, describes a DFU and explains why they benefit from specialist multidisciplinary treatment centres. “DFUs have similar features to other ulcers, and often present in the toes and heal areas of the foot with the loss of skin and an exposed base with infection and necrosis. The significant difference is that a DFU usually comes with multiple pathologies, which, in addition to infection, include neuropathy and peripheral vascular disease. DFUs do not heal quickly and often require vascular surgeons working closely with radiologists, orthopaedic surgeons to correct any deformity and a microbiology unit to manage infection,” says Rashid.
Rashid also explains that different therapies are used to heal DFUs. “If the patient has peripheral artery disease (ischaemia) then this has to be treated first with an angioplasty or a bypass or both to improve blood circulation into the foot. Once this is achieved, the ulcer is debrided and dressed. There are different dressings, which include negative pressure dressing, which sucks the blood into the tissues and thereby promotes healing. Sometimes skin graphs are necessary to get the tissue to heal faster. This can be done as a day surgery using local anaesthetic,” says Rashid.
Prevention of DFUs
Given the severity of DFUs and their vast and rapidly increasing burden on individuals with diabetes and healthcare systems, increasing attention is being devoted to prevention, which involves adequate glycaemic control and modification of risk factors. While education is an obligation of healthcare professionals, it is crucial that people living with diabetes themselves increase their awareness and understanding of the condition and integrate regular feet examination and care into their daily lives. In the video below, Roni Sharvanu Saha, Consultant in Acute Medicine, Diabetes and Endocrinology, St George’s Hospital, London, suggests that, “We’re getting better at understanding why DFUs occur, and better at examining peoples’ feet. In England, if you have diabetes you are entitled to a clinical examination of your feet at least twice a year. Checks include whether you have any minor abrasions, or whether you can distinguish hot and cold water with your feet, and signs that you might have problems with your circulation and nervous system. Ensuring that people living with diabetes receive regular checks means that if you have reduced or poor circulation, you’re referred to the correct specialty team in order to protect you from developing DFUs. Prevention is better that cure. If we can get better at examining feet, outcomes will improve. If diabetes is not controlled complications will occur”.
With the well-being of millions of people living with diabetes at stake, there is a pressing need for therapies that bring DFUs to closure as quickly as possible. The current standard of care (SOC) regimen for DFUs involves maintaining a moist wound environment, debriding nonviable tissue, relieving pressure with an offloading boot and preventing or managing wound infection. Even with a good SOC, DFUs are notoriously slow to close, creating a demand for new and innovative medicines and techniques to enhance closure. Increasingly, there are advanced therapies to facilitate healing DFUs when traditional approaches fail.
An example of a relatively new product to help close DFUs is human amniotic membrane. Amniotic membrane has been used for wound healing purposes since the early 20th century, but it represents a relatively recent and promising advanced therapy to accelerate healing in DFUs. Amniotic membrane is derived from the human placental sac that supports the foetus by forming the inner lining of the amniotic cavity. Functions of amniotic membrane include the exchange of water-soluble molecules and the production of cytokines and growth factors to facilitate the development of the foetes. The anatomic makeup of amniotic membrane dictates its functionality, and a significant characteristic is its ability to produce a wide variety of regenerative growth factors that facilitate foetal development. These growth factors, in combination with various other cytokines, have substantial potential benefits in wound healing, which include creating a structural scaffold for tissue proliferation, modulating the immune response, reducing inflammation, stimulating angiogenesis and facilitating tissue re-modelling.
Two small but significant prospective cohort studies on the effectiveness of human amniotic tissue to treat DFUs were reported in the journal Wounds. One in the March 2016 edition and another in the November 2017 edition. The first is a prospective, randomized, multicentre, controlled study and the second a retrospective cohort study of 20 patients. In both studies amniotic membrane is used in combination with SOC, including debridement, well-controlled offloading, management of bacterial burden, and adequate perfusion.
Both studies suggested that the use of amniotic membrane is more likely to: (i) lead to complete wound closure, (ii) accelerate the rate of wound closure, and (iii) present no additional safety risks when compared to SOC alone in the treatment of DFUs. The first study demonstrated a statistically significant advantage of an amniotic membrane as compared to SOC in facilitating closure of chronic DFUs. 45% of participants achieved complete wound closure, while 0% of SOC participants alone achieved complete wound closure within 6 weeks. Further, there appears to be no increased rate of adverse events associated with the use of amniotic membrane in these wounds. The second study was a retrospective cohort study using a human amniotic membrane on 20 patients presenting with DFUs and venous leg ulcers. Patients underwent a 2-week ‘run-in’ period with good SOC; and if upon their return the ulcer had closed ≥ 30% in area, the subject was excluded from participation in the study. All wounds were effectively closed in approximately 10 weeks, DFUs in 12 weeks and venous leg ulcers in 9 weeks, and no adverse events were noted, suggesting that the therapy using human amniotic membrane is safe.
The most significant limitation of both studies is their small sample size, which decreases the generalizability of their findings. Notwithstanding, the studies suggest that amniotic tissue products are efficacious options for DFUs when used in conjunction with the current SOC, which includes aggressive sharp debridement, adequate offloading and the application of sterile dressings. Further, amniotic membrane, like most biologic tissue products, requires significant processing and therefore its cost is relatively high: on average between US$500 to US$1,000 per application. Notwithstanding, these costs are significantly less than the average annual therapy cost of US$28,000 per patient for SOC for a DFU. And therefore, using amniotic tissue in the therapy for DFUs could result in significant savings for healthcare systems. Tissue storage as well as the time and skill required to apply amniotic membranes also represent challenges inherent to these products.
Millions of people are living with diabetes, which, if not managed appropriately can lead to life-changing complications. A DFU is one such complication, which often starts with a minor abrasion on your ankle or toe that you do not feel and therefore tend not to perceive to be important, until that is, it quickly escalates into a chronic wound that does not heal and eventually leads to a lower limb amputation. In most wealthy nations, health providers are aware of the dangers of DFUs and have set up multi-disciplinary diabetic foot clinics to treat and manage the condition. However, access to such clinics is patchy and the prevalence of DFUs continues to increase, and the eye-watering costs of treating and managing DFUs continue to escalate. In recent years, the therapy for DFUs has been improved by technological advances. We describe one of these: the use of amniotic tissue in conjunction with standard of care protocols. Recent research findings suggest that the use of amniotic tissue holds out the possibility not only of significant therapeutic benefits, but also of substantial cost savings for healthcare systems. Notwithstanding, perhaps the most efficacious therapy for DFUs is prevention. This means investing in effective education and awareness programs, good glycaemic control and appropriate footwear; encouraging people living with diabetes to participate in regular foot examinations and screening for peripheral neuropathy and peripheral arterial disease, and insisting that early telltale signs of foot wounds, no matter how minor, should be immediately referred to a specialist clinic.
- Hydrocephalus is a chronic condition that occurs when excess cerebrospinal fluid (CSF) collects in your brain’s ventricles and increases pressure inside your head
- Failure to treat the condition can lead to morbidity and death
- First line therapy is the surgical insertion of a ventriculoperitoneal shunt (VPS) to restore your CSF circulation
- A significant risk with the procedure is infection
- To reduce infection manufacturers’ impregnate standard shunts with either silver or antibiotics and market the impregnated shunts at higher prices
- Which VPS (standard, silver or antibiotic) provides patients with the most protection from infection?
- Which VPS is most cost effective for healthcare systems?
“It” is Hydrocephalus; a chronic condition that occurs when excess cerebrospinal fluid (CSF) collects in your brain’s ventricles, (fluid-filled areas). CSF disperses from your ventricles around your brain and spinal cord. Too much CSF may result in an accumulation of fluid, which can cause the pressure inside of your head to increase. In a child, this causes the bones of an immature skull to expand and separate to a larger-than-normal appearance.
There are no medical therapies to effectively treat hydrocephalus. The only viable treatment is surgical. The gold standard therapy is the insertion of a ventriculoperitoneal shunt (VPS), which is a common surgical procedure to restore your CSF circulation, regulate its flow and allow you to have a normal daily life. Notwithstanding, a significant challenge is infection at the site of the surgical wound, the shunt or in the cerebrospinal fluid itself (meningitis). This effects about 15% of hydrocephalus patients and may result in further surgeries, extended hospital stays, a reduction in your quality of life and a significant hike in healthcare costs.
To reduce potential infection manufacturers’ impregnate standard shunts with either silver (silver has benefits in reducing or preventing infection) or antibiotics and market the impregnated shunts at higher prices.
There are two principal classifications for hydrocephalus: (i) communicating and (ii) non-communicating hydrocephali. Both can be subdivided into congenital (present at birth) and acquired (occurs following birth). Communicating hydrocephalus can also be subdivided into normal pressure hydrocephalus (NPH) and hydrocephalus ex-vacuo, which occurs when there is damage to your brain caused by stroke or injury. It is generally understood that congenital hydrocephalus can be caused by genetic defects, which can be passed from one or both parents to a child, but the direct hereditary links are still being investigated. Notwithstanding, experts have found a connection between a rare genetic disorder called L1 syndrome and hydrocephalus. L1 syndrome is a group of conditions that mainly affects the nervous system and occurs almost exclusively in males.
Most babies born with hydrocephalus or who develop hydrocephalus as infants will have a normal lifespan, and approximately 40 to 50% will have normal intelligence. Seizure disorders have been diagnosed in about 10% of children with hydrocephalus and the mortality rate for infants is approximately 5%.
In the video below Sanj Bassi, a Consultant Neurosurgeon at King’s College Hospital, London and a member of the London Neurosurgery Partnership, describes hydrocephalus:
Signs and symptoms
In the video below Bassi describes how hydrocephalus is diagnosed:
A shunt consists of two thin, long flexible hollow tubes, called catheters, with a valve that keeps fluid from your brain flowing in the right direction and at the proper rate and thereby reduces brain pressure to a safe level. To install a shunt a surgeon will make a small insertion behind your ear and also drill a small borehole in your scull. One catheter is then threaded into one of your brain’s ventricles through the hole in your scull, and the other is inserted behind your ear and threaded subcutaneously down to your chest and into your abdomen where excess CSF can drain safely, and your body can reabsorb it. Your surgeon may attach a tiny pump to both catheters and place it under the skin behind your ear. The pump will automatically activate to remove fluid when the pressure in your skull increases. Shunts can be programmable (externally adjustable by a magnetic device) to activate when the fluid increases to a certain volume, or non-programmable. Most surgeons tend to choose a programmable model, despite the fact that in clinical studies both types perform comparably.
To determine the relative clinical benefits and cost-effectiveness of the three different ventriculoperitoneal shunts (standard, silver or antibiotic) following their de novo insertions, the UK’s National Institute for Health Research funded a large prospective multi-centre randomised controlled clinical study - The British Antibiotic and Silver Impregnated Catheters for Ventriculoperitoneal Shunts Study - (BASICS). Findings were published in the September 2019 edition of The Lancet. These concluded that shunts impregnated with antibiotics significantly reduce the risk of infection and also healthcare costs compared to both standard shunts and those impregnated with silver. Conor Mallucci, Consultant Paediatric Neurosurgeon at Alder Hey Children’s Hospital, Liverpool, UK, and lead author of the study, suggests that shunts impregnated with antibiotics should be, “the first choice for patients with hydrocephalus undergoing insertion of their first ventriculoperitoneal shunt”.
All shunts used in the study were CE marked medical devices intended for the condition. Participants were randomly assigned to three groups: one group of 536 received a standard shunt, another of 531 received a silver impregnated shunt, and a third group of 538 received an antibiotic impregnated shunt. The minimum patient follow-up period was six months and the maximum two years. Six per cent of evaluable patients in both the standard and silver groups presented with infections and required a shunt revision. This compared to only 2% in the antibiotic impregnated shunt group that became infected and needed revising. The difference is significant.
The Study’s economic findings
The research has a further significance because, despite the high medical costs of treating hydrocephalus, the annual spend on hydrocephalus research is relatively low. For example, the US National Institutes of Health (NIH) invests less than US$8m per year in hydrocephalus research. This means that there is a dearth of clinical studies associated with the condition and no long-term follow-up research over the lifetime of patients.
Although BASICS is a significant study it should be mentioned that it is restricted by the relatively low proportion of patient-reported outcomes: 32, 31 and 12 reported infections after insertion of the standard, silver and antibiotic VPS’s respectively.