Archive for ‘healthcare’

June, 2014

Clinical Trials in Skin Cancer at the CRCTU

Dr Joshua Savage (@joshsavage)

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About 115,000 people are diagnosed with skin cancer every year in the UK. The majority of these cases are the non-melanoma types of disease, such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), although there are rarer sub-types of the disease. Despite being very common, non-melanomas are less life threatening and are often successfully treated if caught early, which is more achievable compared to other cancers due to the visibility and palpable nature of skin cancer.

Around 13,000 patients have the more serious, and often more aggressive, malignant melanoma which results in over 2000 deaths per year. In the last 30 years, the rate of malignant melanoma has risen faster than any of the other 10 most common cancers, and its incidence is disproportionately higher in younger people compared to other cancers, with a 1/3 of cases being in people under 55. As with all cancers, there are many risk factors involved in the development of the disease but sun exposure is thought to be the main cause, with most lesions occurring on sun exposed areas of skin. Genetics, namely skin colour, and a history of sunburn and the use of sunbeds also increase the risk of the disease.

There have been great improvements in the treatment of malignant melanoma in the last 30 years, with 5 year survival now at 84% for men and 92% for women. These patients are usually treated with surgery then a combination of radiotherapy and chemotherapy. Earlier this month, very promising results were presented at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago and widely covered in the media, for a “ground-breaking” new immunotherapy by pharmaceutical company Merck, called MK-3475, or more commonly known as pembrolizumab. This drug works by targeting PD-1, or Programmed Death receptor, a protein used by cancer cells to avoid detection by the immune system. This is one of several drugs in a new class of treatments called ‘immune checkpoint blockers’, that ‘modulate’ the immune system allowing the body’s own defences to combat the disease in a more targeted manner than conventional chemotherapy that non-discriminately kills rapidly dividing cells. Currently, 1 year survival for advanced melanoma is 10% for men and 35% for women; encouragingly, 70% of patients on pembrolizumab were still alive after 1 year. These exciting developments are welcome news that will hopefully result in new treatments and a change in standard care for this group of patients who previously had a very poor prognosis.

At the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham, we have a growing portfolio of skin cancer trials. UKMCC-01, is a phase II study using pazopanib to treat patients with metastatic merkel cell carcinoma (MCC), a very rare (400 patients per year in UK) and aggressive form of non-melanoma cancer with a poor prognosis after first line treatment. Pazopanib is currently licensed in the UK to treat advanced renal cell carcinoma and works by targeting platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, amongst other targets, both which have been shown to be mutated or over-expressed in MCC tumours.

We will also soon be opening another phase II trial called SPOT; Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments. SPOT aims to prevent the development of cutaneous SCC from actinic keratoses, asymptomatic red scaly lesions on sun exposed areas of the skin, which are generally regarded as precursors to cSCC. This feasibility study will examine how patients cope with two different topical treatments, 5-fluorouracil and imiquimod versus standard care (sunscreen). SPOT will observe this in a sub-set of patients who have received organ transplants and are taking immunosuppressive medication to prevent organ rejection. These patients have previously been shown to have a much higher incidence of cSCC and other cancers, which once again demonstrates the vital role that the immune system plays in combatting cancer.

Researchers at the CRCTU are working with colleagues across the science and research community to maximise on developments and ensure they reach patients rapidly and change the course of this devastating disease. Novel treatments along with early diagnosis and prevention are key to changing the course of this cancer, Justine a survivor of skin cancer reminds us why we must continue with this plight.

Dr Joshua Savage is a Trial Coordinator at Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham. Follow Dr Savage on Twitter @joshsavage

Further useful links:

June, 2014

How the CRCTU is addressing overtreatment of ductal carcinoma in situ (DCIS)

Miss Claire Gaunt

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The NHS Breast Screening Programme was established in the late 1980’s with the aim of detecting invasive disease at an early stage and reducing deaths from breast cancer. This has been achieved but, an incidental consequence has been the increasingly common finding of DCIS, a diagnosis almost unheard of before mammographic imaging. Historically, DCIS was thought of as a form of early breast cancer that would become an invasive breast cancer if left untreated.

DCIS describes abnormal cells in the milk ducts of the breast. It is divided into 3 types; low, intermediate and high grade. Low grade DCIS looks similar to normal breast cells and high grade DCIS looks similar to cancer cells. When diagnosed, all DCIS is currently removed by surgery because of concern that it may progress to an invasive cancer. If DCIS is indeed an early form of breast cancer, then removing it would have lead to a decrease in the incidence of invasive breast cancer. This has not been the case but, surgical treatment of DCIS, often mastectomy, has remained unchanged since the 1950’s, despite evidence that removing DCIS does not prevent invasive cancers. DCIS is almost always diagnosed as a result of calcification found on mammograms and accounts for 20% of all breast ‘cancers.’ Evidence shows that many women are being treated for a condition that will never become a clinical problem if left undiagnosed. This is known as ‘overdiagnosis’ and ‘overtreatment’. Experts agree that not all untreated DCIS will become breast cancer.

An independent review of the UK National Health Service Breast Screening Programme reported on the benefits and harms of breast screening. This concluded that breast screening saves lives but acknowledged the existence of overtreatment. Consequently, randomised trials were recommended to elucidate the appropriate treatment of screen-detected DCIS and to gain a better understanding of its natural history. The aim of overtreatment trials is to stop treating women who do not need treatment and to better treat those who do.

The Low Risk DCIS Trial (LORIS) is a large phase 3 trial designed to address the recognised issue of overtreatment of low risk DCIS. This trial is not for patients with high grade (the most common) DCIS.

The study is being run by the Cancer Research UK Clinical Trials Unit (CRCTU) which has a long history of running successful breast cancer treatment trials and is an integral part of the Birmingham Surgical Trials Consortium (BiSTC) at the University of Birmingham. The trial is led by Miss Adele Francis, Consultant Surgeon at the University Hospitals Birmingham NHS Foundation Trust. The trial will recruit almost a 1000 women with low risk DCIS, who will be randomised to the current standard treatment which is surgery or to omit surgery and have active monitoring with annual mammograms. The LORIS trial, through it’s clinical and translational research will establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (both psychological and physical) and whether those patients who do require surgery can be identified by pathological and radiological means. When this trial is reported, patients and clinicians will be able to make an informed choice about treatment options.

University Hospitals Birmingham NHS Foundation Trust will be the first centre to begin recruit patients in to this ground-breaking trial. In the coming months, you can follow our progress on twitter at @CRCTU

Miss Claire Gaunt is a Team Leader in the Cancer Research UK Clinical Trials Unit at the University of Birmingham.

Further useful links:

June, 2014

Quality Management at the Cancer Research Clinical Trials Unit (CRCTU)

Isobel Hawley – Quality Assurance Manager

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When I was a child my father drummed into me the importance of paying attention to detail. His actual words were, “always pay absolute attention to absolute detail”. I remember a lot of rolling of eyes (on my part), but he was right (and still is for that matter – thanks Dad!). Now it’s my job to pay attention to detail – as Quality Assurance Manager at the Cancer Research UK Clinical Trials Unit (CRCTU). It certainly wasn’t what I was planning when I graduated with a degree in Russian and French…but many years later, my focus in life changed when a friend’s 3 year old child died of cancer. My previous mild interest in things medical (a lifelong addiction to watching Casualty on Saturday nights) developed into an earnest desire to make a contribution to cancer research, and in 2006 I applied for a job as a Clinical Trial Monitor at CRCTU in the University of Birmingham and I’ve been a member of the Quality Management Team ever since.

Clinical Trials are vital for improving cancer treatments and making them available to patients. The Quality Management Team plays an important role in supporting the conduct of clinical trials at CRCTU, by developing and maintaining a Quality Management System which provides a framework of Standard Operating Procedures, tools and templates to assist all staff in conducting trials to the highest possible standards and ensures adherence to relevant legislation. In the UK, the conduct of clinical trials of Investigational Medicinal Products (trial drugs) is governed by complex legislation and guidance including the 2004 Medicines for Human Use (Clinical Trials) regulations, the Data Protection Act, the Research Governance Framework, Good Clinical Practice and the Declaration of Helsinki.

The regulator in the UK is the MHRA (Medicines and Healthcare Products Regulatory Agency) and CRCTU is subject to inspection at regular intervals. The legislation has recently undergone a review and will soon be replaced by a new European Clinical Trials Regulation which aims to speed up and streamline the conduct of trials across Europe. It is hoped that the new Regulation will achieve its aims – many of the paediatric trials coordinated by CRCTU need to embrace international collaboration in order to recruit sufficient patients to complete the trial in an appropriate timeframe; recently the BEACON trial for children with neuroblastoma opened to recruitment in France and will open in further European countries over the coming months.

Our team of dedicated Monitors travel the length and breadth of the UK, visiting the hospitals where the clinical trials take place. The team is currently responsible for on-site monitoring of more than 30 trials, across multiple diseases (breast cancer, prostate cancer, lung cancer, leukaemia, sarcoma and all paediatric cancers) including the AdUP prostate cancer trial mentioned in Monday’s blog and the STOMP trial for lung cancer patients discussed in Tuesday’s blog. The Monitors meet with the Clinicians and Research Nurses to discuss the trial, providing training, updates and feedback from the Trials Office and a friendly face to help out with any queries. They perform checks on the paperwork at the hospital site – reviewing the medical notes of the trial patients to ensure that all patients are eligible for the trial according to the protocol criteria, checking that the patients have given their written consent to participate in the trial, that the correct trial treatment protocol has been followed and any adverse effects of the treatment have been reported to CRCTU. These on-site monitoring visits help to safeguard the rights and well-being of the trial patients and ensure high-quality data is obtained for analysis by the trial statisticians, ultimately leading to evidence-based improved treatments for patients with cancer.

Further useful links:

June, 2014

Early Phase Clinical Trials in Lung Cancer at the CRCTU

Dr Laura Crack

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Lung cancer is a devastating and very common healthcare problem. Lung cancer is the biggest cause of cancer death in the UK, accounting for more than one in five cancer deaths and is the second most common cancer in both men and women. Recent campaigns such as the plain packaging campaign aim to reduce the numbers of people smoking, particularly targeting children and young adults. Whilst these campaigns targeting environmental and lifestyle factors are crucial to reducing incidence of lung cancer, new and more effective treatments are urgently needed to increase the chances of surviving this devastating disease.

The Cancer Research UK Clinical Trials Unit (CRCTU) has designed and run many clinical trials for both main types of lung cancer (small cell and non-small cell lung cancer) patients over the past 2 decades. A good example of this is in small cell lung cancer (SCLS), the STOMP Trial, which is investigating the safety and activity of a drug (Olaparib) which prevents cancer cells from repairing damage to their DNA; by inhibiting a molecule called PARP. This trial, led by Professor Penella Woll, is actively recruiting patients around the country. The STOMP trial is due to run for another year and will be asking if Olaparib can be used as maintenance therapy for people with SCLC, whether it can increase the length of time people live with the disease and can it be used as maintenance therapy for SCLC.

Because of this expertise, the CRCTU and the University of Birmingham’s Gary Middleton, Professor of Medical Oncology, have been selected to lead on the National Lung Matrix trial; a joint initiative between the University of Birmingham, Cancer Research UK with pharmaceutical partners AstraZeneca and Pfizer. This trial will utilise an existing network of Experimental Cancer Medicine Centres (ECMCs) across the UK to deliver a plethora of drugs to lung cancer patients. Patients will be stratified according to genetic abnormalities in their cancer. This information will be generated in phase 2 of Cancer Research UK’s Stratified Medicine Programme, which was launched in April this year. The trial is due to open to recruitment later in 2014. Once open the National Lung Matrix trial will see cancer treatment moving towards the promise of personalised medicine where a patient’s treatment is guided by the individual genetic make-up of their cancer.

This advancement has been made possible through the Cancer Research UK Stratified Medicine Programme which has looked to establish a network for nationwide molecular testing that will form a vital platform to launch future targeted treatments. Colleagues in Birmingham have been acting as a technology hub for the stratified medicine programme and are in an excellent position to help inform this new stage of cutting edge early phase clinical trials.

TraxerX is another exciting example of the rapidly developments in personalised medicine for lung cancer patients across the country. Researchers in Birmingham are working with nationwide colleagues to further their understanding of lung cancer, how it adapts and responds to treatment along with where its Achilles heels are.

A new era is dawning and Lung Cancer researchers and clinical teams are pushing boundaries to change the devastating effects of a lung cancer diagnosis. Birmingham’s CRCTU is working collaboratively with many leaders in the field to ensure that effective developments reach patients faster.

Dr Laura Crack is EDD Team Leader in the School of Cancer Sciences at the University of Birmingham.

Further useful links:

 

 

June, 2014

Spotlight on the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham

Mr Clive Stubbs and Dr Steve Johnson

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Hello and welcome to the first contribution to this blog from The Cancer Research UK Clinical Trials Unit (CRCTU), which forms part of the School of Cancer Sciences at the University. Over the next five days we are going to share with you some of the exciting clinical research being done at the unit. We will also be touching on related topical events throughout the week.

The CRCTU is one of the largest cancer trials units in the UK and has been in existence for more than 30 years. We are one of three trials units at the University that form the Birmingham Centre for Clinical Trials and also form an integral part of the Birmingham Experimental Cancer Medicine Centre. The unit receives core funding from Cancer Research UK.

We specialise in the design, conduct and analysis of all phases of trials, from phase I, largely concerned with the safety of treatments, all the way through to phase IV cancer clinical trials, looking at the long term risks and benefits of treatments.We work with a wide range of investigators nationwide and internationally in a number of specialist areas including Breast cancer, Lung cancer, Paediatric cancer, Skin cancer and Urological cancer.

The CRCTU has experience in trials involving pharmaceutically active substances, the testing of new treatments on human subjects for the first time, radiotherapy, devices, surgery, allogeneic stem cell transplantation, gene therapy, immunotherapy and biomarker discovery and development.

With this week being international men’s health week, we thought it fitting to focus on two prostate cancer trials that are the product of our unit, one that has closed to recruitment and one that began recruiting patients just over a year ago.

Prostate cancer is by far the most common cancer in men (excluding non-melanoma skin cancer), accounting for one in four cases. In 2011 in the UK, over 41,000 men were diagnosed with the disease. Whilst being relatively indolent, with most men dying with prostate cancer rather than because of it, almost 11,000 men died from their prostate cancer in 2011.

The ‘Trapeze’ study, an academic clinical trial for patients who have Prostate Cancer which has spread to include the bone (metastatic prostate cancer), was coordinated by The CRCTU with Professor Nick James the Chief Investigator and is now closed to recruitment.

This trial compared different combinations of treatment in patients whose prostate cancer that had spread to the bones and had not responded to hormone therapy, to determine whether or not the upfront use of bone targeting agents with chemotherapy improves clinical outcomes.757 patients took part. The trial started out as a ‘Phase II’ study, investigating the effectiveness of giving docetaxel together with prednisolone, with or without zoledronic acid and/or radioactive strontium and the side effects.This was then expanded into a phase III trial with a larger number of patients. This is a novel approach, as normally differing phase trials are separate.

The results, presented at the American Society of Clinical Oncology meeting in 2013 showed that radiotherapy with injectable strontium given after chemotherapy with docetaxel, increased the length of time until the disease progressed. In addition, it was shown that zoledronic acid significantly reduced the average time until the occurrence of ‘skeletal-related events’ caused by bone metastases. These ‘events’ include pathological fractures, spinal cord compression, or the need for radiation or surgery to the bone. Further health economic and quality of life analyses are pending.

Another exciting prostate cancer trial that is being run by the CRCTU and has recently opened is the ‘AdUP’ trial, investigating a new gene therapy treatment that helps the body’s own immune system fight prostate cancer, in addition to targeted ‘suicide gene therapy’. The trial is aimed at prostate cancer patients whose cancer has returned after being treated with radiotherapy and is no longer responsive to hormone therapy, but remains contained within the prostate. This condition affects around 3,000 patients every year.

The treatment is in 2 parts. The first part is an injection directly into the prostate of modified adenovirus (the virus responsible for the common cold). The virus is unable to replicate in the body and can produce an enzyme called nitroreductase (NR) and an immune agent called GM-CSF. Once inside the cells, one of the genes carried by the virus causes the cells to produce GM-CSF, which activates the body’s own immune system, attracting white blood cells to attack the cancer. Two days later, patients receive an infusion of a drug, which becomes active on coming into contact with NR and starts to kill cancer cells. The aim of this trial is to investigate the safety of this combined treatment.

The modified adenovirus was developed by the Gene Therapy Group, led by Dr. Peter Searle, in the School of Cancer Sciences at Birmingham and has taken 15 years of work with support from the Medical Research Council.

There is currently no approved curative treatment for these patients. The Chief Investigator, Mr Prashant Patel is hopeful that the AdUP treatment could delay or prevent the progression to metastatic disease, offering new hope to patients with prostate cancer.

“If this works, 15 to 20 years from now, we could be using the patient’s own immune system in this way to fight early onset prostate cancer so that patients won’t need painful treatments or even surgery” his colleague Mr Richard Viney said.

Last year when the first patient underwent treatment, the trial made headlines: Cold virus ‘treats prostate cancer’ for Birmingham patient (BBC News).

Though the focus of men’s health week this year is relating to health at work and stress, there are other men’s health and cancer awareness initiatives running throughout the year. Movember is well supported at The CRCTU and from the above video Mr Prashant Patel can be seen supporting the initiative with his Mo proudly!

We hope you found this insight interesting. Coming up in tomorrow’s post, a piece on an exciting and pioneering new project known as the National Lung Matrix trial for patients with advanced lung cancer.

To find out more about what goes on at The CRCTU you can follow our twitter feed here.

Further useful links:

May, 2014

If integration is the answer – what was the question?

Professor Jon Glasby

Over time, governments of all persuasions have sought to achieve more integrated health and social care. This ranges from the Joint Consultative Committees and joint finance of the 1960s and 1970s to care co-ordination in the 1990s, and from New Labour’s emphasis on ‘joined up solutions to joined up problems’ to the Coalition’s promotion of ‘integrated care’. The latest version is a series of ‘integrated care pioneers’ (which the University of Birmingham helped to select), with learning from these sites shared with other areas of the country to promote more holistic care.

Despite all this, we continue to have a very divided health and social care system (even if we have found ways of blurring the boundaries from time to time). Deep down, our approach is based on the assumption that it’s possible – and possibly even desirable – to distinguish between people who are ‘sick’ (who we see as having ‘health’ needs met free at the point of delivery by the NHS) from people who are merely ‘frail’ or ‘disabled’ (who we see as having ‘social care’ needs met by local authorities and subject to means-testing and significant user charges). This may once have made sense – but feels increasingly unsustainable and counter-productive with an ageing society. At best, it causes frustration, duplication and inefficiency; at worst it can lead to people with complex needs falling through the gaps in the safety net which services are meant to provide. Whether it is child protection scandals, mental health homicides or older people discharged from hospital before community services are ready for them, the consequences of not working together can sometimes be catastrophic.

In response, the emphasis on ‘integrated care’ is welcome – but the problem is that this can mean so many different things to different people. It is also becoming something of an automatic policy response (just as ‘partnership working’ did under New Labour) – put forward as a solution to a range of different ills. All too often, this leads to a situation where we use warm words, but where everyone ends up frustrated because no one way of organising could ever deliver all the potentially mutually incompatible aims that individual partners may want to achieve.

As a result, a key contribution which HSMC when working with policy makers and front-line services makes is to ask: if integration is the answer, what was the question? Although this sounds basic, we need to know what we’re trying to achieve before we decide how best to go about organising our service responses. While some sort of co-ordinated effort may be required for some outcomes, a single agency working by itself might be just as effective for other issues. Being clear what success would look like is also a crucial first step to being able to evaluate ‘what works’. However, we often fail to do this – partly because public services have such multiple accountabilities that being clear about what success looks like is really difficult; but also (slightly cynically) because if we aren’t able to be clear about what success looks like, it’s also hard to be clear about what failure looks like. Joint working is also very time-consuming and it takes significant commitment to build long-term relationships. Reserving such a labour-intensive way of working for situations where it will have maximum impact feels crucial.

In the current financial context, it is even more important to work together than ever before – but calling something a ‘partnership’ doesn’t make it so. If we’re not careful, then concepts such as ‘integrated care’ could become an end in themselves, rather than a means to an end – and people using health and social care deserve more than this.

Jon Glasby is Director of the Health Services Management Centre (HSMC) and Professor of Health and Social Care.

For further information, see Glasby, J. and Dickinson, H. (2014) A to Z of inter-agency collaboration and his new book with The Policy Press on Partnership working in health and social care: what is integrated care and how can we deliver it?

Other useful links:

What is integrated care?

Integrated care: A position paper for the WHO

Integrated delivery networks: a detour on the road to integrated health care?

Patients need to be the focus of integrated health care

 

March, 2014

Surviving Burns and Overcoming Burns

Dr Jonathan Reinarz

One of the most interesting aspects of burns work undertaken by Archibald McIndoe during the Second World War (see Wednesday’s post) was the establishment of the Guinea Pig Club. The Guinea Pigs were members of WWII Royal Air Force air crews who had undergone at least two operations for their burns injuries at East Grinstead Hospital, where McIndoe was based. Originally intended to be a drinking club for patients whose injuries could be dangerously dehydrating (see Monday’s post), it counted 39 members at its launch in June 1941, a year after the Battle of Britain. By the end of the war, there were 649 Guinea Pigs, most of whom were British (62%), but it also included Canadians (20%), Australians (6%) and New Zealanders (6%); 80% had served as bomber crew during the war. As war historian Emily Mayhew has suggested, the Club was ‘an attempt to institutionalise the unique spirit of the patient community at East Grinstead’ in order to aid the psychological recovery of burn victims. Patients collectively attended operations, assisted newcomers and otherwise offered support to each other when necessary.

‘Dealing with Disfigurement’

Rather than hide away these severely disfigured airmen, McIndoe considered both their physical and (as he termed it) psychical wellbeing. He recognised that patients relied on their surgeon ‘for mental support, for hope and encouragement.’ But he also encouraged his patients to resume ordinary lives, often commencing with a joint visit to a local pub. Most wanted to resume normal lives, but their wounds often made this more difficult than expected. McIndoe knew that his patients would inevitably attract much attention the moment they ventured into town to frequent pubs or restaurants, so he prepared the residents of East Grinstead for potential encounters with patients, some of whom were mid-operation, with tube pedicle grafts nearly in place to reconstruct missing chins or noses. He also invited key members of the town into the wards, encouraging them to become ambassadors in the community by regularly hosting concerts and balls, where patients mingled with locals. In this way, he made the residents of East Grinstead recognise and accept his patients and focus on their contributions to society, rather than their disfigurements. In the process, East Grinstead became known as ‘the town that didn’t stare’, while the hospital developed an international reputation for its Maxilla-Facial Unit. The staff was so successful at its work that 80% of aircrew patients eventually returned to flying duties. Such success continued into peacetime, but the details of McIndoe’s civilian work has been less documented. Despite the positive experiences of East Grinstead Guinea Pigs, many inevitably faced challenges when they re-entered their former communities. That said, many had learned how to deal with these difficult encounters from their membership of the Guinea Pig Club; a group of about 60 original members continue to meet.

Psychological support for burns patients has continued to grow since 1941. The emotional load on staff at burns units has also been recognised, with many practitioners expressing their own challenges coping with the onerous duties involved in caring for these unique patients. Unusually, when Guinea Pigs visited America following the war, their faces were kept out of the press for fear of alarming the public. Americans would inevitably learn about the psychological impact of burns in their own ways. The 1942 Coconut Grove nightclub fire in Boston was not the worst urban fire in twentieth-century America, but it had a huge impact on burns treatment. Besides directing attention to the consequences of inhalation injury, it provided valuable insights into the immediate and long-term psychological impact of severe burns and the importance of supporting patients after their physical wounds healed. As obvious as some of these lessons were, it seems they need to be relearned every decade or so. More often these days, the memories of disasters, collective and individual, are kept alive by patient groups. Many American victims of burns and scalds owe their emotional recovery to the Phoenix Society for Burn Survivors, a national organisation dedicated to burns patient support, public education and advocacy.  In Britain, patients with burns receive the support of similar organisations, including Changing Faces, BurnAid and the Katie Piper Foundation. So successful have burns units become at saving humans that their challenges have shifted. Many victims now expect medical teams to save lives and even restore former appearances. It is with such expectations that support groups also help a new generation of patients.

New portrait of Simon Weston recently unveiled at the National Portrait Gallery.

New portrait of Simon Weston recently unveiled at the National Portrait Gallery.

Jonathan Reinarz wishes to thank Emily Mayhew, Rebecca Wynter, Naiem Moiemen, Tony Metcalfe, Shah Mamta, Ken Dunn and James Partridge for their help with his research.

Dr Jonathan Reinarz is Director of The History of Medicine Unit and a Reader in the History of Medicine at the University of Birmingham.

March, 2014

Burns and Infections: The Birmingham Accident Hospital

Dr Jonathan Reinarz

Nearly 60% of burns patients die of infections contracted after their initial injuries. Historically, burns-related infections have proved particularly challenging. Burn wounds contain devitalised tissue and remain moist and warm during the healing process, thus an excellent breeding ground for bacteria. In the early twentieth century, burns did not appear to respond to existing antiseptic methods. Many doctors believed that burns themselves released toxins and attempted to neutralise these by treating burns with dyes and acids, which often hindered recovery. As a result, many practitioners continued to regard the infection of burns as inevitable.

In the 1940s, important research in this field began to be undertaken in the English midlands at Birmingham Accident Hospital. When an existing general hospital on Bath Row in the city centre was moved to facilities behind the newly constructed Birmingham Medical School in 1938, the old site was renovated and reopened in 1941 as the Birmingham Accident Hospital. (Incidentally, the site was also the last voluntary (or charity) hospital established in England and Wales before the introduction of the National Health Service). The new hospital’s Surgeon-in-Chief and Clinical Director William Gissane (1898-1981) regarded this as an experiment in the care of trauma in order to improve local accident services, which were inadequate across the country. At the outbreak of the Second World War and the associated production of military hardware, this had become obvious; the incidence of local industrial injuries, including burns, increased by 40%. During 1943, a small unit to treat burns and scalds was opened, and Gissane invited Leonard Colebrook (1883-1967) to be its first Director. Like Gillies (see yesterday’s post), Colebrook was a veteran of the Great War and contributed to a Government-appointed war wounds sub-committee run by Archibald McIndoe during the Second World War. Colebrook had investigated the bacteriology of wounds at the burns unit at Glasgow Royal Infirmary, where he had previously investigated puerperal sepsis in maternity cases. He therefore had experience of both burns and streptococcal infections when called on by Gissane to run the Medical Research Council-funded unit.

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‘The Topical and the Local’

On arrival, Colebrook quickly turned to the investigation of streptococcus infections in burns. With new topical anti-microbial agents, such as penicillin and propamide, he and his team managed to reduce the prevalence of these infections to 5%. Controlling infection, whether through topical creams, or ventilated wards and bandaging stations, allowed for new burns treatments, such as early excision, which is still described as an important measure to prevent infection as well as disfiguring contractures. When he retired in 1948, Colebrook turned to organising local and national burns prevention campaigns, focusing, for example, on safer electrical heaters and the introduction of less flammable clothing for children.

Colebrook’s successor was Edward Lowbury (1913-2007), who became bacteriologist at what was later renamed the MRC Industrial Injuries and Burns Research Unit in 1952. Among other things, Lowbury initiated the first properly controlled clinical trials in burns, and infection rates continued their downward trend, until the emergence of antibiotic-resistant bacteria in the late-1950s. The introduction of silver nitrate in 1966 halted this rise, but rates would continue to fluctuate, as safer alternatives were introduced. By 1963, the burns unit had already become a large regional centre comprising 36 beds, a ‘clean air’ dressing station and expanding research facilities, with Lowbury compiling a unique record of resistance changes until his retirement in 1979. Treating over 18,000 burned patients between 1941 and 1993, the burns unit developed a planned, systematic approach to the treatment of these injuries, which greatly reduced the frequency of associated infections.

Problems of infection in hospitals in the wider Birmingham region led to the establishment of the Hospital Infection Research Laboratory in the grounds of Dudley Road Hospital (later City Hospital) in 1964. Administered by the MRC Burns Unit and under the direction of Lowbury, the laboratory assessed the number of infections in regional hospitals, determining causes when possible. Although the Accident Hospital closed its doors in 1993, the Infection Control Research Laboratory continues to exist in a new location. Many of its earlier recommendations for controlling infection are still in place today. With the laboratory celebrating its 50th anniversary this year, staff have organised a commemorative conference, and the History of Medicine Unit at the University of Birmingham has organised an exhibition on ‘the history of hospital infection’, which will be on display in the foyer of the Medical School until the summer.

Dr Jonathan Reinarz is Director of The History of Medicine Unit and a Reader in the History of Medicine at the University of Birmingham.

 
March, 2014

War burns and the birth of plastic surgery

Dr Jonathan Reinarz

The majority of historical research into burns has concentrated on the remarkable reconstructive work undertaken on burns casualties during the First and Second World War. In fact, some argue that plastic surgery as a specialty first emerged during the First World War. Soldiers in both wars sustained horrific injuries and dreadful deformities from high velocity missiles, explosives and burns, many of which would previously have defied repair. A young ear, nose and throat (ENT) surgeon from New Zealand, Harold Delf Gillies, began the war in a surgical unit at the Cambridge Hospital, Aldershot. Alarmed by the number of face and jaw reconstructions he was having to perform, Gillies visited two plastic surgeons in France before setting up a larger surgical unit in 1917 at Sidcup, where he brought together a team of specialists, including ENT colleagues and dental surgeons. Gillies is best remembered for the tubed pedicle, a flap of skin which was harvested from the arm or chest, for example, stitched into a tube, so as to retain a blood supply and gradually migrated to the area where it was required. By the end of the war, Gillies had developed many other surgical techniques and performed over 11,500 operations. Many of these are included in his best known publication, Plastic Surgery of the Face (1920), which, along with Gillies’s archives, has recently been digitised and made available online as part of activities to mark the centenary of the First World War.

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From Airman’s Burns to Hiroshima

In one of those accidents of history that historians have become used to over the years, many severe burns in the Second World War were placed in the hands of another young surgeon, Archibald McIndoe, who happened to be the cousin of Harold Gillies. Unlike most of the casualties seen by cousin Harold, McIndoe treated primarily flame injuries that largely resulted from a decision to relocate the petrol tanks of fighter aircraft in front of the cockpit and pilot. The consequences of placing 48 gallons of fuel in the nose of a Spitfire rapidly became apparent during the Battle of Britain in 1940, when burn casualties mounted and the medical community defined a new injury, ‘Airman’s Burn’. Nearly 400 Royal Air Force (RAF) crew sustained serious burns to their face and hands in 1940 alone, Richard Hillary becoming perhaps the best known due to his memoir, The Last Enemy, in which he described his injuries.

‘I looked at my watch: it was not there. Then for the first time I noticed how burnt my hands were: down to the wrists, the skin was dead white and hung in shreads: I felt faintly sick from the smell of burnt flesh.’

While the smell of burn victims and high fatality associated with serious burns had led many to be isolated, removed or even excluded from nineteenth-century hospital wards, Hilary was lucky to be treated in a specialist burns unit by one of only four plastic surgeons operating in Britain at this time (including Gillies who would spend his second war at Park Prewitt Hospital in Basingstoke). Appointed civilian consultant surgeon to the RAF, McIndoe became responsible for Hillary and many other air-force casualties at a surgical unit which was established in a cottage hospital in East Grinstead, 40 miles outside of London. Here, he treated hundreds of burned airmen and developed surgical techniques in order to improve on existing plastic surgery techniques, which often left much to be desired. According to Mcindoe, in these early years of reconstructive surgery ‘the end result seemed to convert the pathetic into the ridiculous’. Rarely satisfied with his first attempts, McIndoe worked 12-hour days and frequently subjected his patients to more than a dozen operations. He rapidly became recognised as the authority in the field, influential in developing new operations and discarding older treatments, such as the use of tannic acid to coat burns injuries. He hosted many visiting surgeons at East Grinstead, which had trained 60 surgeons by 1943, and secured his reputation in 1944 when 50 North American plastic surgeons attended his unit for ten days to train in preparation for the D-Day landings. He also increased the levels and training of nurses on his wards and introduced saline baths into burns treatment.

After the 1945 atom bomb attacks on Japan, the attention of doctors turned to the impact of modern warfare on both military and civilian casualties. McIndoe himself argued that burns would likely outnumber all other injuries in future wars. McIndoe’s colleagues similarly promoted such ideas, suggesting that ‘atomic flash’ burns necessitated whole hospitals be transformed into burns units, arguments reinforced in the aftermath of Hiroshima and Nagasaki and during the Cold War. Many more units like that at East Grinstead were established in the 1950s, and McIndoe continued to work in his 50-bed Burns Centre at East Grinstead until his retirement in 1959. In a lecture to the Royal College of Surgeons in 1958, he comprehensively outlined his views on reconstructive surgery and paid homage to ‘the greatest plastic surgeon of all times’, Harold Gillies. McIndoe died in 1960, aged 59. A statue is being planned to recognise his work; if realised this will be one of only three existing British public monuments in England commemorating surgeons.

Dr Jonathan Reinarz is Director of The History of Medicine Unit and a Reader in the History of Medicine at the University of Birmingham.

March, 2014

Burns: A riot in the body

Dr Jonathan Reinarz

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You can imagine, as a medical historian, much of my research centres on ‘Saving Humans’. When I was asked to contribute to this blog, though, one particularly timely subject immediately leapt out: burns. I began researching burns last year in the British context for the years 1800 to 2000, and, in that time, the public has been reminded of the subject with regular reports of acid attacks, house fires, wars, suicides and revolutions. More than many other subjects I have researched, burns are both timeless and very timely. In June 2013, the Burns Collective was launched in Birmingham, creating a national centre for burns research linking hospitals in London, Bristol and the ‘Second City’. I attended the inaugural conference and instantly found myself fascinated by papers outlining current practices, research and priorities. Though the history of burns remains to be explored, they should also be familiar to all of us. Unlike many diseases and accidents which will thankfully remain a mystery to most of this blog’s readers, we have all experienced burns. However prevalent or timely, burns are also particularly suited to a blog managed by the University’s Institute of Advanced Studies. Like the IAS, which aims to bring together scholars from across the University of Birmingham’s various academic disciplines, burns are unique in the way they bring together people from across medicine’s many specialties. 

In a previous project, I had the opportunity broadly to explore the medical, social and cultural history of the skin. At its most basic, a burn is an injury of the skin, the body’s largest organ (though some now call it a ‘multi-organ’). Addressing burns and scalds only in passing, the project reminded us that burns are prominent in the cultural imagination, and have been so for hundreds of years. Neither are they confined to the realm of the dermatologist. Besides contributing significantly to the way in which we conceive of ourselves and others, the skin has many essential functions: it regulates the passage of fluids in and out of the body; it helps synthesis vitamin D, while shielding the body’s interior from ultraviolet radiation; it is a barrier that prevents disease-causing organisms from entering the body, while simultaneously receiving sensations which it passes on to the brain via the nervous system. As a result, when the skin is burned, whether by hot tea, a sunburn, or following more serious flame, electrical or chemical accidents, we experience pain, and much else that is more than just skin deep. The skin’s many features and functions are invariably compromised by burns, and people’s identities may be changed forever. The more serious the burn – anything larger than 10% total body surface area is considered a major burn – the more violent the body’s response. It is for this reason that burns have been described as ‘a riot in the body’. All bodily systems potentially respond to serious burns, especially if the victim also experiences smoke inhalation.

What is a burn?

The immediate aftermath of a severe burn is shock and suffocation, both related to a lack of oxygen. Plasma normally circulating in the blood surges to the tissues, leaving the blood thicker and prone to clotting. During the 24-hours following a burn, the affected area grows progressively more swollen; this is the period when blisters form. Fluid must be replaced to restore circulation and dilute the toxins being expelled in greater amounts by the kidneys (one formula used to help calculate fluid replacement was developed by Basil Pruitt, who attended the Birmingham congress). In the nineteenth century, the oozing appearance of burns might have led doctors to introduce treatments which only encouraged dehydration. As a result of these physiological changes, the body is less able to regulate temperature and shock ensues. One by one, the major organs are compromised by the loss of liquids. When the respiratory system is effected, breathing becomes difficult and the body deals with lower cardiac output by pumping more blood. The additional effort required to do so sends the body into a hypermetabolic, or catabolic, state, and it begins to break down tissues, burning protein as well as fat. As body mass decreases, the patient becomes more susceptible to infection and wounds also heal more slowly. The destructive increase in metabolism, on the other hand, is countered by feeding the patient amounts of food that might ordinarily be regarded as excessive. And, importantly, the whole process is not over in a day or two. Burns are an acute illness that lasts weeks or even months. Treatment of burns patients therefore becomes an intensive life-saving process, which these days extends beyond the immediate survival of the burned individual, and aims for full psychological recovery, involving psychiatrists, physiotherapists and social workers, among many other specialists and professionals. It is for this reason that victims of severe burns are treated in burns units. According to the British Burns Association, there are currently 27 specialised burn units in Britain. In the 1930s, more than half of major burns cases in this country might have died from their injuries. Today, 97% of approximately 16,000 people hospitalised for burns each year survive this ordeal.

Dr Jonathan Reinarz is Director of The History of Medicine Unit and a Reader in the History of Medicine at the University of Birmingham.

 
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