Secondary Projects | NIHR SRMRC - Surgical Reconstruction and Microbiology Research Centre

CRASH-4

webteam — Wed, 18 May 2022 12:36:48 +0000

A fall from standing height in older adults is the commonest cause of major trauma in the UK. Traumatic brain injury (TBI) accounts for half of trauma admissions in older adults and is a leading cause of death and disability. Because the UK population is steadily ageing, the number of older adults with TBI will continue to rise. Most (90%) of the 1.4 million TBI patients seen each year in emergency departments in England and Wales have mild (Glasgow Coma Scale (GCS) score 13-15) head injury, but the term ‘mild’ is misleading in older adults who have higher death rates and worse outcomes than younger patients. Due to increased use of anticoagulant and antiplatelet drugs, older adults are more likely to suffer intracranial bleeding after mild TBI. TBI is also a strong risk factor for dementia in older adults. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. Results from randomised trials (CRASH-3 and NCT01990768) show that early treatment with TXA reduces head injury deaths (pooled RR 0.89, 95% CI 0.80-0.99). In the CRASH-3 trial, the reduction in head injury deaths with TXA was largest in patients with mild and moderate head injuries, particularly if patients were treated soon after
injury. However, the CRASH-3 trial included mild TBI patients only if they had intracranial bleeding on CT scan. It is uncertain whether the results apply to mild TBI patients more generally. Intracranial bleeding occurs soon after injury and early treatment is most effective. We have shown that TXA is rapidly absorbed after intramuscular injection in trauma patients without local side effects. This means that paramedics can give intramuscular TXA before transport to hospital, and for those who do not travel by ambulance, intramuscular TXA can be given immediately on hospital arrival. If early intramuscular TXA treatment reduces death and disability in older adults with mild TBI this would be a major medical advance that would improve the care of many millions of patients in the UK and world-wide.

AspiFlu

webteam — Wed, 18 May 2022 12:20:38 +0000

Some patients with seasonal Influenza (‘flu’) develop severe infection requiring admission to the Intensive Care Unit (ICU) to support their breathing. Recent research has suggested that when patients have such severe influenza they may be susceptible to a second infection with a mould (a type of fungus) called Aspergillus. The mortality for patients infected with both severe ‘flu and Invasive pulmonary Aspergillus (IPA) is high but life-saving antifungal treatments exist and thus it is important that a diagnosis of IA in patients with severe influenza is not missed. Unfortunately, IPA can be difficult and lengthy to diagnose in the laboratory and until recently it was only thought to occur in patients whose immune systems were severely impaired. This means that IPA in patients with severe influenza may be under-diagnosed currently and the main aim of this study is to establish how common this condition is in UK patients.

In 2020 a new coronavirus was identified as the cause of an outbreak of unexplained pneumonia in China. This coronavirus was later named ‘SARS-CoV-2’, and the disease it causes ‘COVID-19’. It is not yet known whether patients with severe COVID-19 infection are also at risk of IPA. This study offers an excellent opportunity to understand the risk of developing IPA in COVID-19 and find out whether fungal infection is contributing to the high death rate of COVID-19 patients in the ITU. An increased risk of IPA may not just apply to these two severe viral infections of the lung- it may also be that a heightened risk of secondary Aspergillus infection applies to any patient on the ICU with severe lung infection. In order to best understand this, we also plan to enrol patients on ICU with bacterial lung infection (pneumonia)as a control group so that we can compare the rates of IPA between patients with influenza, COVID19 and bacterial infections on the ICU.

BOSS-2

webteam — Wed, 18 May 2022 12:14:54 +0000

Hypertrophic scarring (HTS) is the single major contributor to physical and psychological difficulties not only to burn survivors, but also to people with trauma and surgical scars. Management of HTS is an enormous challenge to all health professionals, due to a lack of strong evidence of the benefits of different treatments, and, an absence of objective methods of scar assessments to evaluate those different treatments. Although there are several modalities of scar management, including; massage , topical silicone , pressure garment , intra-lesion injection of steroids or other anti-metabolite and, more recently, laser therapy or fat injections, none has thus far demonstrated sufficient evidence of clinical efficacy or cost effectiveness.

SMOOTH

webteam — Wed, 18 May 2022 11:26:19 +0000

Burn injury is the fourth most common type of trauma after road traffic accidents, falls and interpersonal intentional injury. In 2004 it was estimated that worldwide 11 million people suffered fire-related burn injury with 265,000 deaths annually. Burns are also one of the leading causes of disability-adjusted life-years lost. Crucially, up to 90% of the patients who survive a burn injury suffer significant scarring, with hypertrophic scars predominating. Burn care during the last 30 years has seen a step change in survival and this increased survival has been paralleled by improved acute care and durable wound cover resulting in less deformity and scarring. However, there remains an urgent need for improvements in post-burn scar assessment, management and the treatment of historic scars. We suggest that improved understanding of the mechanisms that mediate scar reduction with laser treatment, combined with standardised assessment of scarring and rigorous RCT design, will enable better design of laser treatment regimens and thus benefit those living with hypertrophic scarring.

MAST

webteam — Wed, 18 May 2022 10:56:07 +0000

Acute symptomatic seizures are potentially harmful. Recurrent post-traumatic seizures (PTS) after traumatic brain injury can negatively impact on quality of life, return to work/driving, and can even lead to death. Anti-Epileptic Drugs (AEDs) are the mainstay of treatment for patients with PTS but are associated with side effects that, if serious, can negatively impact on quality of life, cognition, and general health. Patients with acute symptomatic seizures are typically started on an AED in order to prevent seizure recurrence. The optimal duration of treatment remains unclear. MAST-DURATION will compare a long course of AED (at least 6 months) vs a shorter course (up to 3 months). MAST-PROPHYLAXIS will compare a 7-day course of AED (either levetiracetam or phenytoin) versus no AED.

FAME

webteam — Wed, 18 May 2022 10:40:28 +0000

Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many
patients experience pain and physical impairment, with the consequences of the fracture and its
management lasting for several months or even years. The broad aim of ankle fracture treatment is to
maintain the alignment of the joint whilst the fracture heals and to reduce the risks of problems such as
stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances
in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of
function and quality-of-life is considerable. Non-surgical treatment is an alternative to surgery and involves
applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint; the
key benefit being a reduction in the frequency of common complications of surgery. The main potential
risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function.

P2X7

webteam — Mon, 14 Feb 2022 13:20:39 +0000

Traumatic brain injury (TBI) is commonly associated with falls, road traffic accidents and assaults, and is the leading cause of death and disability in the first four decades of life. For those patients who survive, there are frequently long-term complications, such as chronic pain, epilepsy, and paralysis. The current standard of care centres upon neurosurgical intervention and stabilisation, but despite the obvious unmet clinical need, there are no approved pharmacological treatments available to reduce the impact of TBI and improve the longer-term outcomes.

Whilst it would be difficult for a drug to reduce the actual injury, it is well recognised that inflammation caused by the initial trauma spreads to the surrounding brain tissue resulting in an expansion in the area and volume of brain damage. This ‘secondary’ brain damage has been well-studied using animal models. It begins within hours to days after the initial TBI event and is considered amenable to potential treatment with drugs.

This 3-year study is funded by the Medical Research Council (MRC) and will offer the opportunity to build on the knowledge gained from animal models by examining human brain tissues and cells in vitro. The participants (approximately 150 in total) will be patients undergoing neurosurgery at the Queen Elizabeth Hospital Birmingham (QEHB) consented for the donation of samples arising from routine surgical procedures.

OPTIMAS

webteam — Tue, 14 Dec 2021 12:12:09 +0000

Atrial fibrillation (AF) has a lifetime risk of 1 in 4 in European populations, and increases the risk of ischaemic stroke 4-5 fold. About 1 in 5 strokes are caused by AF (over 20,000 strokes per year in the UK). In AF- associated acute ischaemic stroke, the risk of early recurrence (within 7-14 days) is high, between 0.4% and 1.3% per day.

AF-associated ischaemic strokes are more often disabling or fatal than other types of stroke, with
longer hospital stays and higher costs, so preventing early recurrence is a key clinical challenge.

Direct Oral Anti-Coagulants might allow safe and earlier clot-busting after acute ischaemic stroke in patients with AF, providing net benefit by reducing ischaemic stroke recurrence without increased risk of bleeding into the brain. The OPTIMAS clinical trial aims to test this hypothesis.

RANGER

webteam — Tue, 12 Oct 2021 14:22:22 +0000

The intent of this multicenter, registry study (ANG-CP-005) is to capture data on injury, repair, safety and outcomes for processed nerve allografts (Avance® Nerve Graft, Axogen, Corporation) in today’s clinical practice.

CONTACTS

webteam — Tue, 12 Oct 2021 14:08:16 +0000

Previous work suggests that concussion remains underdiagnosed in the Emergency Department and patients are rarely adequately followed up in clinical practice. This may reflect the complex nature of diagnosing and monitoring concussion but may also demonstrate the lack of NHS resources allocated towards mild Traumatic Brain Injury care. It is important therefore to assess whether well-established sports-related concussion (SRC) assessment tools may be translated into the non-sporting population of the NHS. If validated, these tests could provide invaluable additional information to clinicians, not only in diagnosis but in monitoring recovery and managing this complex condition. Whilst previous studies have utilised both the SCAT and ImPACT in non-athlete patients, no study to date has addressed translatability into the NHS. To determine whether these tools can be translatable, they must be tested in groups that are reflective of the patients who suffer concussive injury. Elderly and intoxicated patients should also be assessed. A longer-term qualitative review of the tools would add depth to existing data and indicate the willingness of non-athletes to engage in these tests using telephone and email reviews.