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Take a look at a selection of our recent media coverage:
3rd October 2023
Two of the four internationally recommended sepsis screening tools used by emergency medical services (EMS) are inadequate for recognising the condition, according to a new study presented at the European Society of Emergency Medicine (EUSEM)‘s recent congress.
The study also highlighted that both EMS and emergency physicians should be more vigilant in documenting a suspicion of sepsis so that further clinical patient assessment and evaluation can take place. This could help the condition to be diagnosed and treated earlier, which could help to save lives and maintain patients‘ quality of life.
Researchers from the Charité – Universitätsmedizin Berlin and the universities of Magdeburg and Jena in Germany, aimed to assess which of four screening tools recommended in the Surviving Sepsis Campaign guidelines was best for emergency medical services (EMS) to predict the condition.
They found only the National Early Warning Score (NEWS-2) screening tool to have a reasonably accurate prediction rate for sepsis. A second tool – the quick Sequential Organ Failure Assessment (qSOFA) – had a high level of accuracy in predicting patients who did not have it.
However, the two other standard screening tools, Systemic Inflammatory Response Syndrome (SIRS) and the Modified Early Warning Score (MEWS), performed poorly in both sensitivity and specificity of sepsis detection.
Dr Wolfgang Bauer, senior physician at the Charité, said: ‘In emergency care, there are good and long-established standards for the detection and treatment of heart attacks and stroke that have improved patients’ chances of survival. Unfortunately, a lot less attention is paid to sepsis and standards to improve early sepsis recognition and survival.
‘Our study found there was a similar incidence for sepsis (1.6%) as for heart attacks (2.6%) and stroke (2.7%) in cases seen by emergency medical services. However, in terms of both percentages and absolute numbers, more patients died from sepsis than from heart attacks or stroke.
‘Out of all cases with sepsis, 31.4% died within 30 days after being seen by emergency services, versus 13.4% and 11.8% respectively for heart attacks and stroke. These findings emphasise the need for better sepsis awareness and more frequent use of effective screening tools.‘
The retrospective cohort study linked data on 221,429 emergency care cases, with follow-up between 2016 and 2017 from 10 health insurance companies, with information from documentation by paramedics and emergency doctors. In doing so, it was possible to calculate the ability of the four tools to predict a sepsis diagnosis.
Only the NEWS-2 had a reasonably accurate prediction rate for sepsis, with it able to correctly predict 72.2% of all cases (sensitivity) and correctly identify 81.4% of negative, non-septic cases (specificity).
In contrast, the qSOFA had a much lower sensitivity (24.1%) but a high specificity (96.6%) for identifying those without sepsis.
For SIRS, the corresponding sensitivity and specificity were 30.4% and 93.8%, respectively, and for MEWS they were 46.8% and 88.4%.
In total, 24.3% of cases were predicted to have sepsis by at least one of the screening tools, and only 0.9% of cases were predicted to have the conditon by all four tools.
The predictions were confirmed or rejected during subsequent hospital investigations after contact with EMS.
Silke Piedmont, a health scientist for the Department of Emergency Medicine, Campus Benjamin Franklin at the Charité, and first author on the abstract said: ‘We found that paramedics never documented a suspicion of sepsis, and emergency services physicians rarely did so, only documenting a suspicion in 0.1% of cases. The screening tools recommended in the Surviving Sepsis Campaign guidelines differed greatly in terms of which and how many patients were identified as possibly having sepsis.’
Emphasising the need for better awareness and more frequent use of screening tools, Ms Piedmont added: ‘No screening tool provides ideal performance. NEWS-2 best supports EMS in identifying most patients with sepsis. EMS patients that are NEWS-2 positive should be flagged up as potentially having sepsis and referred for special attention and assessment by emergency doctors who are expert in sepsis. If EMS insist on using the qSOFA, they should be aware that a positive qSOFA makes sepsis likely, but also that a negative qSOFA cannot rule out sepsis conclusively.
‘A rule of thumb for EMS staff could be that NEWS-2 negative patients are the most likely not to have sepsis, and qSOFA positive patients are the most likely to have sepsis – and also that qSOFA misses many patients with sepsis.‘
The researchers hope their findings will help to inform new guidelines on the condition, which are being drawn up in some countries to give more specific recommendations for its screening. In particular, Ms Piedmont said: ‘Future sepsis guidelines should be more precise and omit recommendations for MEWS and SIRS for EMS since they were inferior in all the measures for accuracy.’
These findings could also apply to other countries, the researchers suggest, especially as previous studies performed in Canada and the UK support aspects of their results.
‘Ours is the first study comparing all four screening tools and showing the predictive usefulness of applying the screening tools to all adult patients independently of any presumptions or preliminary diagnoses by EMS,‘ said Mrs Piedmont.
2nd October 2023
Tailoring opioid prescriptions for patients discharged from an emergency department (ED) with acute pain can support recovery and help to avoid the risk of drug misuse, according to a study presented at the European Society of Emergency Medicine (EUSEM)‘s recent congress.
The study found half of patients discharged from an ED with acute pain required five tablets or fewer of morphine 5 mg or an equivalent opioid painkiller to help manage their pain and recover from their injury or condition at home.
By tailoring the number of opioid painkillers prescribed for each patient, ED clinicians can ensure the right balance between sufficient pain relief and avoiding the over-prescribing of these drugs, which can lead to dependence and abuse in some cases.
Professor Raoul Daoust, from the University of Montreal, Canada, who presented the research, said: ‘Opioids such as morphine can be very beneficial for patients suffering acute pain, for example when they have injured their neck or broken a bone. However, patients are often prescribed too many opioid tablets and that means unused tablets are available for misuse. On the other hand, since the opioid crisis, the tendency in the USA is to not prescribe opioids at all, leaving some patient in agonising pain.
‘With this research I wanted to provide a tailored approach to prescribing opioids so that patients have enough to manage their pain but almost no unused tablets available for misuse.‘
Some 2,240 adult patients were recruited for the study, all of whom were treated at one of six hospital EDs in Canada for a condition that causes acute pain. They were each discharged with an opioid prescription and were asked to complete a pain medication diary for the following two weeks.
While half of patients took five 5 mg morphine tablets or fewer, the researchers noted that the number of tablets each patient required during the two-week period varied greatly according to the patient’s painful condition. For example, patients suffering from renal colic or abdominal pain needed only eight tablets and patient with broken bones needed 24 tablets.
Professor Daoust added: ‘Our findings make it possible to adapt the quantity of opioids we prescribe according to patient need. We could ask the pharmacist to also provide opioids in small portions, such as five tablets initially, because for half of patients that would be enough to last them for two weeks.’
Also commenting on the results, Professor Youri Yordanov from the St Antoine Hospital emergency department in Paris, France, who is chair of the EUSEM 2023 abstract committee but was not involved in the research, added: ‘It’s estimated that millions of people around the world are struggling with opioid addiction and more than 100,000 people die of opioid overdose every year. These drugs play an important role in emergency medicine, but we need to ensure they are prescribed wisely.
‘This study shows how opioid prescriptions could be adapted to specific acute pain conditions, and how they could be dispensed in relatively small numbers at the pharmacy to lower the chance of misuse. This research could provide a safer way to prescribe opioids that could be applied in emergency departments anywhere in the world.‘
Although widely prescribed in an emergency setting, a recent study has found that using opioids for patients with acute low back or neck pain offers no significant pain relief advantage compared to placebo.
28th September 2023
Methotrexate (MTX) is an effective treatment for children with severe atopic dermatitis and provides more sustained disease control than ciclosporin (CyA) upon discontinuation, according to the findings of a recent randomised controlled trial.
In the TREAT trial, published in the British Journal of Dermatology, a team led by King’s College London, set out to examine the safety and efficacy of these two main first-line conventional systemic immunosuppressive therapies in children and young people with severe atopic dermatitis.
The parallel group, assessor-blinded randomised trial included 103 participants aged between two and 16 years of age whose atopic dermatitis was unresponsive to potent topical treatment.
The participants were randomised to receive either 4 mg/kg/day of CyA or 0.4 mg/kg per week of MTX for a total of 36 weeks. They were also followed up for 24 weeks.
The co-primary endpoints were the change from baseline to 12 weeks in the Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to a first significant flare (relapse) after treatment cessation.
Among the 52 participants assigned to CyA, there was a greater improvement in disease severity by 12 weeks (mean difference o-SCORAD = -5.69 p = 0.01). In fact, more participants reached o-SCORAD-50 at 12 weeks in the CyA arm compared to the MTX (Odds ratio, OR = 2.60, 95% CI 1.23 – 5.49, p = 0.01).
However, by week 60, MTX was superior (OR = 0.33, 95% CI 0.13 – 0.85, p = 0.02). Furthermore, participant-reported post-treatment flares were higher in the CyA arm (OR = 3.22, 95% CI 0.42 – 6.01, p = 0.025) and both treatments gave rise to a similar level of serious adverse events.
The researchers also highlighted that MTX is significantly cheaper than CyA and concluded that MTX is a useful and safe treatment in paediatric patients with severe atopic dermatitis and a good alternative to CyA, especially in settings where healthcare resources are limited.
Until now, there has been no adequately powered randomised clinical trial evidence in relation to the safety and treatment success of methotrexate and ciclosporin for paediatric patients with atopic dermatitis. With new high-cost therapies being introduced, establishing a gold standard for treatment with the conventional systemic therapies like methotrexate and ciclosporin is deemed necessary.
Commenting on these findings study author Professor Carsten Flohr, chair in dermatology and population health sciences at King’s College London and consultant dermatologist at St John’s Institute of Dermatology, part of Guy’s and St Thomas’ NHS Foundation Trust, said: ‘This is the largest paediatric trial using conventional immuno-modulatory treatments in severe atopic dermatitis and was conducted across 13 centres in the UK and Ireland and is likely to change our treatment paradigm around this condition, not just for patients in the UK but also internationally.‘
27th September 2023
The diagnostic ability of the artificial intelligence system ChatGPT is similar to that of emergency department clinicians when examining some complex diagnostic cases, according to the findings of a new study presented at the European Society of Emergency Medicine (EUSEM)‘s recent congress.
Simultaneously published in the Annals of Emergency Medicine, the study used data from 30 undiagnosed patients who were ultimately given a single proven diagnosis.
The research team retrospectively investigated the ability of ChatGPT to generate accurate differential diagnoses based on the physician notes recorded at the initial emergency department presentation. The patient data was fed into two versions of ChatGPT: the free 3.5 version and the 4.0 subscriber version.
Clinicians correctly included the diagnosis in the top five differential diagnosis for 83% of cases. For ChatGPT v3.5 this was 77% and for v4.0 was 87%. Furthermore, the correct diagnosis was included within clinician‘s top five likely diagnoses in 87% of the cases, which compared favourably to the 97% for ChatGPT version 3.5 and 87% for version 4.0.
When laboratory results were included in the assessment, clinicians chose the correct leading diagnosis in 53% of the cases, which was of comparable accuracy to ChatGPT v3.5 at 60% and v4.0 at 53%.
Commenting on these diagnostic results, lead author, Dr Hidde ten Berg said: ‘We found that ChatGPT performed well in generating a list of likely diagnoses and suggesting the most likely option. We also found a lot of overlap with the doctors’ lists of likely diagnoses. Simply put, this indicates that ChatGPT was able suggest medical diagnoses much like a human doctor would.
‘For example, we included a case of a patient presenting with joint pain that was alleviated with painkillers, but redness, joint pain and swelling always recurred. In the previous days, the patient had a fever and sore throat. A few times there was a discolouration of the fingertips. Based on the physical exam and additional tests, the doctors thought the most likely diagnosis was probably rheumatic fever, but ChatGPT was correct with its most likely diagnosis of vasculitis.’
Professor Youri Yordanov from the St Antoine Hospital emergency department in Paris, France, who is chair of the EUSEM 2023 abstract committee but was not involved in the research, added: ‘We are a long way from using ChatGPT in the clinic, but it’s vital that we explore new technology and consider how it could be used to help doctors and their patients.
’People who need to go to the emergency department want to be seen as quickly as possible and to have their problem correctly diagnosed and treated. I look forward to more research in this area and hope that it might ultimately support the work of busy health professionals.
ChatGPT is an artificial intelligence system that is being increasingly explored in healthcare, although its value is currently varied. For example, it has shown some promise for relatively straightforward questions in cardiology but performed less well in more complex vignettes.
25th September 2023
Cancer screening is designed to detect the presence of disease at an early stage, but whether it actually has the desired effect of reducing mortality is up for debate. Clinical writer Rod Tucker investigates.
In medicine, screening is designed to identify the presence of a disease in healthy individuals who are not displaying any of the typical clinical signs or symptoms of a particular condition. Cancer screening, for instance, can therefore be considered to serve a dual purpose: on the one hand it is preventative, but it can also enable the early identification of cancer or precursor lesions and thus having the potential to improve prognosis.
Cancer screening is already well established for breast, prostate, lung, cervical and colorectal cancers, and many of the current tests are very accurate. For example, one novel prostate cancer screening test has an accuracy of 94%.
The fact that cancer screening has the potential to reduce cancer-related mortality and ultimately improve lifespan, has been the main focus in public health messaging. In the past, such messaging has been emotive, employing powerful and persuasive tools such as fear and guilt, engendering a sense of personal responsibility and convincing individuals to be screened.
And this approach has clearly worked. For instance, in a survey of 500 individuals that included women over 40 years of age and men over 50 years, without a history of cancer, the majority (87%) believed that routine cancer screening was almost always a good idea. In addition, 74% felt that finding a cancer early, through methods such as screening, saved lives most or all the time.
But does cancer screening actually extend lifetime? Five-year survival is often presented to the public as evidence of the value of early detection, but one analysis concluded that changes in five-year survival over time bear little relationship to changes in cancer mortality.
A recent meta-analysis attempted to shed further light on the relationship between cancer screening and all-cause mortality, which offered some surprising results.
Most randomised controlled trials of cancer screening focus on disease-specific mortality as the outcome of interest. However, the validity of this outcome is highly dependant on an accurate ascertainment of death, which is not always clear.
This was highlighted in an analysis of 12 published randomised trials of cancer screening for which disease-specific and all-cause mortality data were available. The researchers identified major inconsistencies in both disease-specific and all-cause mortality but concluded that since all-cause mortality is not affected by bias in classifying the cause of death, it should be used as the main outcome of interest for randomised trials looking at cancer screening.
The most recent study to examine of the impact of cancer screening on all-cause mortality was conducted by a team based at the Institute of Health and Society, which is part of the University of Oslo in Sweden. The researchers performed a systematic review and meta-analysis of randomised clinical trials that reported on all-cause mortality to estimate the potential lifetime gained for six commonly used cancer screening tests when compared to no screening.
They focused on mammography screening for breast cancer; colonoscopy, sigmoidoscopy or faecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; and prostate-specific antigen (PSA) testing for prostate cancer.
The team included trials with 10 to 15 years of follow-up and set the primary outcome of interest as lifetime in the screened group compared to the non-screening group based on all-cause mortality. Using these differences, the researchers calculated the absolute lifetime gained in days.
With the inclusion of just over 2.1 million individuals in the analysis for the six different cancer screening trials, the only screening test with a significant lifetime gain of 110 days (95% CI 0 – 274) was sigmoidoscopy. However, the lower 95% confidence interval extended to zero, so the effect was just significant.
Although there were gains in lifetime accrued for prostate (37 days) and lung (107 days) cancer screening, these increases were not significant.
Despite these largely negative findings, the researchers were quick to point out that they did not actually favour abandoning screening, merely that the current evidence did not substantiate the claim that common cancer screening tests saved lives by extending lifetime.
Although all-cause mortality has been suggested as a better study endpoint, a problem with using this metric is that the impact of screening on all-cause mortality, depends largely on the level of underlying risk of death from different causes, such as heart disease, within the population being screened.
Consequently, while there are clearly some limitations from focusing solely on cancer-related deaths as an outcome, this may be preferable with the caveat that deaths from other causes are carefully reviewed to identify potential cases of harm.
Nonetheless, a 2015 analysis concluded that currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and either very rare or non-existent for all-cause mortality.
The use of all-cause mortality as a primary outcome may be more relevant for the multi-cancer early detection test, especially if deaths from the cancers targeted constitute a high proportion of expected deaths in the population recruited.
Perhaps the most important message from the recent cancer screening analysis is that in their discussions with patients, clinicians should no longer predicate the rationale for screening on the claim that it will both save lives and increase life expectancy. This may not always be the case.
The kinase inhibitor ruxolitinib (brand name Jakavi) has been recommended in draft guidance by the UK’s National Institute for Health and Care Excellence (NICE) for the treatment of patients with the blood cancer polycythaemia vera (PV), its manufacturer Novartis has announced.
The endorsement covers the approved oral indication of ruxolitinib for the treatment of PV in adults who are unable to tolerate the standard treatment of hydroxycarbamide, or when the condition is resistant to it.
Commenting on the approval, Dr Claire Harrison, consultant haematologist at Guy’s and St Thomas’ NHS Foundation Trust in London, said: ‘There is a significant unmet need for people with polycythaemia vera in England and Wales, who live with a large symptom burden as a result of their condition.
‘[This] decision is a step in the right direction for providing additional treatment options that reduce the burden of these symptoms and improve disease progression, in this under-represented patient population.‘
Jon Mathias, co-chair of MPN Voice – a charity that supports and advocates on behalf of PV patients – added: ‘We welcome this recommendation from NICE, as polycythaemia vera can be an extremely debilitating illness that has a significant impact on patients’ lives in terms of day-to-day symptoms.
‘It affects not only patients but also their families and carers and turns many everyday tasks into major hurdles. Ruxolitinib addresses a significant unmet need in patients who cannot tolerate or no longer respond to HC/HU.‘
In 2015, a phase 3 randomised trial showed that in patients with PV who had an inadequate response or unacceptable side effects from hydroxycarbamide, ruxolitinib was superior with respect to controlling the haematocrit, reducing the spleen volume and improving associated symptoms.
Moreover, ruxolitinib has also been shown to be efficacious and well tolerated in PV patients who were previously treated with interferon.
PV is rare blood cancer affecting the bone marrow. A myeloproliferative disorder, it involves uncontrolled red blood cell production resulting in an elevated red blood cell mass. The condition affects an estimated 1,130 people in the UK every year and the underlying cause of the disease is related to dysregulation of the JAK-STAT pathway. Typically, patients have an elevated haematocrit, leading to blood thickening, increasing the risk of blood clots, as well as higher white blood cell and platelet count.
Ruxolitinib is an inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was recently approved in the UK in a topical form as a treatment for non-segmental vitiligo in adults and adolescents with facial involvement.
18th September 2023
Three studies presented at the recent European Respiratory Society (ERS) International Congress in Milan, Italy, highlight the various damaging effects of air pollution in early childhood, including on birthweight and the incidence of respiratory infections.
According to a recent consensus statement from the European Respiratory Society on climate change, there is likely to be a disproportionately greater negative impact from global warming on individuals living with respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
One of the most important and detrimental consequences of climate change is the resulting increased levels of air pollution, which is already known to damage the lungs and have other negative consequences such as mental health issues in dementia.
Now, three related studies presented at the ERS International Congress have shed further light on the deleterious effect of air pollution. The studies reveal how pollution not only reduces the birthweight of newborns, but also increases the incidence of respiratory infections experienced by young children.
In the first study (abstract PA311), researchers sought to investigate the association of maternal exposure to air pollution based on what they described as the level of environmental ‘greenness’ during pregnancy, and whether this affected birthweight.
They devised a measure of greenness termed the ‘normalised difference vegetation index‘ (NDVI), which was based on the density of vegetation seen on satellite images. In addition, the team modelled exposure to five known pollutants: nitrogen dioxide (NO2), ozone, black carbon (BC), and two types of particulate matter (PM2.5 and PM10). The levels of these pollutants were estimated for mothers based on their residential address during pregnancy.
The researchers analysed data on 5,434 children from 2,742 mothers. The median NDVI300m was 0.3 (interquartile range, IQR, 0.2 – 0.4). Increases in the level of greenness were positively associated with birthweight. For example, each IQR increase in NDVI300m was associated with an increase in birthweight of 29g, a 23% lower odds of a low birthweight (Odds ratio, OR = 0.77, 95% CI 0.64 – 0.94), as well as a 14% increased odds of a high birthweight (> 4000g) (OR = 1.14, 95% CI 1.02 – 1.26).
Commenting on the findings, lead author, Robin Mzati Sinsamala, a researcher in the department of global public health and primary care at the University of Bergen (UiB), Norway said: ‘The time when babies are growing in the womb is critical for lung development. We know that babies with lower birthweight are susceptible to chest infections, and this can lead on to problems like asthma and COPD later on.
‘Our results suggest that pregnant women exposed to air pollution, even at relatively low levels, give birth to smaller babies. They also suggest that living in a greener area could help counteract this effect. It could be that green areas tend to have lower traffic or that plants help to clear the air of pollution, or green areas may mean it’s easier for pregnant women to be physically active.’
In the second study (abstract PA311), which was published in the journal Pediatric Pulmonology, a UK team from Sussex Medical School and University Hospitals Sussex NHS Foundation Trust sought to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood.
Researchers turned to data from the GO-CHILD prospective birth cohort study, which explored the role of environment and gene variation on infection and atopy-related outcomes. As part of the study, pregnant women were recruited and their children followed up for infection and respiratory symptoms and outcomes after 12 and 24 months via postal questionnaires.
Information was available for 1,344 children, and the researchers identified how several environmental factors and settings were significantly associated with respiratory infections. For example, use of daycare facilities was associated with a more than two-fold increased risk of pneumonia (odds ratio, OR = 2.39), wheeze (OR = 2.16) and a dry cough (OR = 2.01). There was also a higher risk of developing bronchiolitis (OR = 1.40).
The presence of visible damp in the home increased the risk of wheeze (OR = 1.85) and led to a two-fold increased risk of being prescribed an inhaled corticosteroid (Relative risk, RR = 2.61).
Air pollution also contributed to the risk of respiratory problems. The presence of dense traffic around the child’s home, increased the risk of bronchiolitis (OR = 1.32). However, it was found that the harmful effects of environmental pollution could be mitigated to some extent by measures such as breastfeeding. In fact, continuing to breastfeed beyond six months was associated with a significantly reduced odds of bronchiolitis (OR = 0.55).
Commenting on this study, lead author, Dr Tom Ruffles from the Sussex Medical School, said: ‘This research provides some important evidence about how we can help reduce chest infections in babies and toddlers. The benefits of breastfeeding are well-established, and we should continue to support mothers who want to breastfeed their babies. We should also be making every effort to reduce exposure to infections in daycare, keep homes free of damp and mould, reduce tobacco smoking and cut air pollution.’
Finally, researchers in the third study (abstract PA2721), who were part of the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) based at Gentofte Hospital and the University of Copenhagen in Denmark, looked at the level of respiratory infections seen in children who had been born in either a rural or urban location.
Using the COPSAC2010 mother-child cohort, researchers followed the participants from pregnancy until three years of age and recorded whether the children were growing up in urban or rural areas and how many respiratory infections they developed. The researchers also performed an analysis of the airway immune profile in the children at age four weeks and undertook both maternal and child metabolomic profiling during week 24 of their pregnancy and two to three days after birth.
Among 663 children, the team found there was a mean of 16.3 infections, which were mainly respiratory in nature. Among children living in an urban area, there was a 15% higher risk of infections compared to those living in rural areas (adjusted incidence rate ratio = 1.15, 95% CI 1.05 – 1.26, p = 0.002).
Urbanisation resulted in a different airway immune profile and it was this change that increased the risk of infections, they concluded. Furthermore, urbanisation resulted in different maternal and child metabolomic profiles, which significantly increased the risk of infections.
Lead author for the study and COPSAC researcher and physician, Dr Nicklas Brustad, said: ‘Our findings suggest that urban living is an independent risk factor for developing infections in early life when taking account of several related factors such as exposure to air pollution and starting day care. Interestingly, changes in the blood of pregnant mothers and newborn babies, as well as changes in the newborn immune system, seem to partly explain this relationship.
‘Our results suggest that the environment children live in can have an effect on their developing immune system before they are exposed to coughs and colds. We continue to investigate why some otherwise healthy children are more prone to infections than others and what the implications are for later health.
‘We have several other studies planned that will look for risk factors and try to explain the underlying mechanisms using our large amount of data.’
14th September 2023
Using lung progenitor cell transplantation in patients with chronic obstructive pulmonary disease (COPD) appears to improve symptoms and could lead to a cure, according to a study presented at the recent European Respiratory Society (ERS) International Congress 2023 in Milan, Italy.
It has been previously shown that P63+ progenitor cells, which are used by the body to repair and replace damaged tissue, are able to induce lung epithelium regeneration in animal models.
Consequently, in this first-in-human phase 1 clinical trial (abstract OA4297), researchers set out to investigate the efficacy and safety of taking autologous P63+ progenitor cells transplanted into the lungs of patients with COPD.
They demonstrated that the use of P63+ progenitor cells in those with COPD enabled patients to breathe better, walk further and have improved quality of life. This is the first time researchers have shown it‘s possible to repair damaged lung tissue in patients with COPD using their own lung cells.
The trial included 17 COPD patients with a diffusing capacity of the lungs (DLCO) of less than 80% of the predicted value and three control patients. Individuals were autologously transplanted with the P63+ progenitor cells through bronchoscopy, followed by subsequent assessment for both safety and efficacy within 24 weeks.
The cell treatment was well tolerated by all patients and following transplantation, the median DLCO of treated patients increased from a baseline value of 30.00% to 39.70% after 12 weeks and still further to 40.30% after 24 weeks.
When it came to quality of life, the average St George’s Respiratory Questionnaire score of those receiving cell therapy group decreased from 51.3% at baseline to 44.2% after treatment. The median six-minute-walk distance increased from 410m to 447m at 24 weeks.
In addition, two patients with mild emphysema showed resolution of the lesions at 24 weeks by CT imaging.
Professor Wei Zuo, chief scientist of the study and professor in the school of medicine at Tongji University, Shanghai, China, told the congress: ‘P63+ progenitor cells are known for their ability to regenerate the tissues of the airways, and previously we and other scientists have shown in animal experiments that they can repair the damaged epithelial tissue in the alveoli.‘
He added: ‘We found that P63+ progenitor cell transplantation, not only improved the lung
function of patients with COPD, but also relieved their symptoms, such as shortness of breath, loss
of exercise ability and persistent coughing. This means that the patients could live a better life, and
usually with longer life expectancy.
‘If emphysema progresses, it increases the risk of death. In this trial, we found that P63+ progenitor cell transplantation could repair mild emphysema, making the lung damage disappear. However, we
cannot repair severe emphysema yet.‘
Commenting on the ‘encouraging‘ results, Professor Omar Usmani, head of the European Respiratory Society group on airway disease and professor of respiratory medicine at Imperial College London, UK, added: ‘COPD is in desperate need of new and more effective treatments, so if these results can be confirmed in subsequent clinical trials it will be very exciting. It is also very encouraging that two patients with emphysema responded so well.
‘A limitation of this study is that the uptake of the progenitor cells when they were transplanted back into the patients is uncontrolled. So we do not know whether the lungs of some patients responded better to the transplantation than other. We hope this information may become apparent in future studies.‘
The researchers are planning a phase II trial of the treatment, which will evaluate its efficacy in a
larger group of patients.
12th September 2023
A total of 26 significant epilepsy risk loci able to explain up to 90% of the genetic risk for certain types of epilepsy have been identified in a new study, which could help to pave the way for new treatments.
In the multi-ancestry genome-wide association study coordinated by the International League Against Epilepsy, researchers used a meta analysis to better understand the differences in the generic architectures between focal and generalised forms of the condition.
The analysis, published in the journal Nature Genetics, considered 4.9 million single-nucleotide polymorphisms (SNPs) in 52,538 controls and 29,944 people with epilepsy, of whom 16,384 had neurologist-classified focal epilepsy and 7,407 had genetic generalised epilepsy (GGE).
The team identified 26 genome-wide significant loci, of which 16 have not been reported previously and 19 of which were specific to GGE. In addition, there were 29 likely causal genes underlying these 26 loci. SNP-based analyses demonstrated how common variants explained between 39.6% and 90% of the genetic risk for GGE and its subtypes.
Commenting on these findings, Professor Gianpiero Cavalleri, professor of human genetics at the RCSI School of Pharmacy and Biomolecular Science, and deputy director of the SFI FutureNeuro Research Centre, which was involved in the research, said: ‘Gaining a better understanding of the genetic underpinnings of epilepsy is key to developing new therapeutic options and, consequently, a better quality of life for the over 50 million people globally living with epilepsy.
‘The discoveries we report on here could only be achieved through international collaboration on a global scale. We are proud of how the global community of scientists working to better understand the genetics of the epilepsies have pooled resources and collaborated effectively, for the benefit of people impacted the condition.‘
The term epilepsy describes a heterogeneous group of neurological disorders characterised by an enduring predisposition to generate unprovoked seizures. It has an annual cumulative incidence of 68 per 100,000 people.
The mechanism through which the different forms of epilepsy arise remain unclear although research in 2022 proposed hypertension as a potential cause. The role of genetics has also been uncertain with previous studies finding that only a limited proportion of cases of GGE can be explained by genetics.
Percutaneous coronary intervention (PCI) combined with implantable defibrillators and optimal medical therapy (OMT) may benefit high-risk heart failure patients with low left ventricular ejection fractions, according to a recent study.
Patients with ischaemic left ventricular dysfunction normally undergo either coronary artery bypass graft or PCI before the insertion of implantable defibrillators. This is based on the assumption that PCI lowers the incidence of potentially fatal ventricular arrhythmias, avoiding the need to insert such defibrillators.
However, a randomised trial by researchers at King’s College London and funded by the British Heart Foundation (BHF) has revealed that PCI does not reliably improve the heart’s ability to pump or reduce the risk of these life-threatening ventricular arrhythmias. As a result, the team has suggested high-risk patients should no longer have to wait the standard 90 days following PCI before assessing the need for insertion of an implantable defibrillator.
Patients with heart failure and a low ejection fraction benefit from a cocktail of drug therapy which includes ACE inhibitors, beta-blockers and amiodarone. Consequently, the study protocol dictated that all patients should receive OMT as part of the standard treatment.
Some 700 patients with ischaemic left ventricular systolic dysfunction were randomised to receive either PCI with OMT or OMT alone. Although the use of an implantable defibrillator was considered to be an integral component of OMT for all patients, the decision to implant such a device was at the discretion of heart teams at recruiting centres.
The researchers set a composite primary outcome of all-cause death or aborted sudden death, which was defined as an appropriate implantable defibrillator therapy or a resuscitated cardiac arrest, at a minimum of 24 months.
The median left ventricular ejection fraction was low at 28%, and 53.1% of patients had an implantable defibrillator inserted before randomisation or during the study follow-up.
All-cause death or aborted sudden death occurred in a similar proportion of patients in each group (hazard ratio, HR = 1.03, 95% CI 0.82 – 1.30, p = 0.80). There was also no between-group difference in the occurrence of any of the secondary outcomes.
Commenting on these findings, one of the research team, Dr Holly Morgan, BHF clinical research fellow at the King’s College London BHF Centre of Research Excellence, said: ‘Our findings have revealed that many patients with a high-risk of heart failure could benefit from receiving an ICD [implantable cardioverter defibrillator device] straight away, rather than facing a 90-day wait.‘
She continued: ‘We hope our findings will influence existing guidance, so patients can be spared unnecessary waits to receive a potentially lifesaving defibrillator.‘
Dr Sonya Babu-Narayan, associate medical director at the BHF, added: ‘The results from this large UK-wide trial could lead to re-evaluation of how best to treat people living with severe heart failure due to coronary heart disease. The findings suggest that the current “wait and see“ approach to find out whether a patients’ heart function improves with medication and stents isn’t always best, and that an unnecessary wait could even be the difference between life and death.‘
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