Frequently need to pee? App-based therapy can help, finds research

Combining pelvic floor exercises with behavioral therapy could be more effective than current medical treatments at helping men with frequent urges to urinate, new research in men has found.

The initial results from the Bladder Emptying Disorder Therapy (BEST) Trial are presented today [Monday 8 April 2024] at the European Association of Urology Congress in Paris. They reveal that an app-based therapy leads to significant improvements in the lower urinary tract symptoms that many millions of men experience – hesitancy, straining, frequent urges to urinate and emptying the bladder effectively. Full results of the trial are expected to be published later this year.

Carried out in Germany, this is the world’s first randomised controlled trial to look at combining pelvic floor training, behavioural therapy and bladder control techniques for mild, moderate and severe bladder emptying disorders in men, all delivered as an app-based therapeutic.

Bladder emptying disorders can start to appear from the age of 30 and typically affect a large proportion of men aged over 50.

While clinical guidelines recommend physiotherapy, behavioural therapy and lifestyle changes as a first-line of treatment, they are often neglected by clinicians due to a lack of available evidence. Several unpleasant side effects are associated with the few drugs available, and surgery is only advised for those with severe symptoms.

Professor Christian Gratzke, from University Hospital Freiburg in Germany, who co-led the trial, explains: “Frequent urges to urinate and issues emptying the bladder are the most prevalent urinary conditions we see in men after urinary tract infections. While some drugs are available, they don’t tend to be effective, and up until now there’s been little data available to back physiotherapy. We’re confident that we now have that data, and making this form of therapy available digitally could be a game changer for the millions of men who struggle day-to-day with issues emptying their bladder.”

The researchers recruited 237 men aged over 18 from across Germany into their 12-week study. Half the men were randomised to receive standard medical care, while the other half were given access to the Kranus Lutera app-based therapy alongside standard care. These participants were asked to record a urination diary, which was used to inform their treatment, and complete questionnaires about the severity of their symptoms and their overall quality of life.

After 12 weeks, the trial found significant and clinically meaningful improvements in symptoms and quality of life measures from participants given the app-based therapy, who reported an average seven-point increase in symptom scores compared to those in the control group.

Crucially, the study found that the app-based therapy was more effective than medical therapy. No patients reported any side-effects or challenges accessing the smartphone app.

The findings challenge the dogma of the 1980’s and 1990’s, when prostrate surgery was the first line of treatment for an overactive bladder, and offer a welcome alternative to drugs, say the researchers.

“Many men with bladder emptying disorders are ageing and have other medical conditions that require drug treatments,” says Professor Gratzke. “The limited drugs we have available aren’t suitable for these patients due to their side effects. For those with mild-to-moderate urinary symptoms, this digital therapy is without side effects and improves symptoms by a magnitude we have not seen before. Simply strengthening the pelvic floor makes all the difference, it’s a no brainer.”

Jean-Nicolas Cornu, Professor of Urology at the Charles Nicolle Hospital in France and member of the EAU Scientific Congress Office, said: “There has been little to no evidence to support training men to better control their bladders, despite this being recommended in clinical guidelines. This is the first randomised controlled trial looking at physiotherapy and behavioural therapy for bladder emptying disorders, and it shows a very positive effect over conventional drug treatment.

“We now need a bigger trial looking at the longer-term effect of this app-based therapy after 12 weeks for different forms of bladder emptying disorders. If offered widely, this treatment could dramatically change clinical practice, and could relieve symptoms without exposing patients to drugs. We could save a lot of unnecessary prescriptions for drugs that tend to be of little benefit.”

The researchers compared data from men whose symptoms were due to overactive bladder with those whose symptoms were due to an enlarged prostate. They found that both groups benefited from the therapy. However, it did not compare the effect of therapy on different forms of bladder emptying disorder.

The research was funded by Kranus Health who was independent of the trial.

Oral vaccine for UTI is potential alternative to antibiotics, finds 9-year study

Recurrent Urinary Tract Infections (UTIs) can be prevented for up to nine years in more than half of people given an oral spray-based vaccine and is a potential alternative to antibiotic treatments, finds research.

Initial results from the first long-term follow-up study of the safety and effectiveness of the MV140 vaccine for recurrent UTIs are presented this weekend at the European Association of Urology (EAU) Congress in Paris.

They show that in both men and women with recurrent UTIs, 54% of study participants remained UTI-free for nine years after the vaccine, with no notable side effects reported. Full results of the study are expected to be published by the end of 2024.

UTIs are the most common bacterial infection. They are experienced by half of all women and one in five men and can be painful and uncomfortable. Recurrent infections, needing short-term antibiotic treatment, develop in between 20 to 30 per cent of cases. With antibiotic resistant UTIs now on the rise and drugs becoming less effective, new ways of preventing and treating these infections are needed.

Carried out by clinicians at the UK’s Royal Berkshire Hospital, this long-term follow-up looked at the safety and efficacy of the MV140 vaccine in 89 patients originally treated privately at The Urology Partnership Reading.

MV140 is a new vaccine for recurrent UTIs and is administered with two sprays of a pineapple-flavoured suspension under the tongue every day for three months. While researchers have previously studied MV140’s short-term safety and effectiveness, this is the first long-term follow-up study to report globally.

Dr Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who co-led the research, said “Before having the vaccine, all our participants suffered with recurrent UTIs, and for many women, these can be difficult to treat. Nine years after first receiving this new UTI vaccine, around half of participants remained infection free. Overall, this vaccine is safe in the long term and our participants reported having fewer UTIs that were less severe. Many of those who did get a UTI told us that simply drinking plenty of water was enough to treat it.”

“This is a very easy vaccine to administer and could be given by GPs as a 3-month course. Many of our participants told us that having the vaccine restored their quality of life. While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”

In their original trial, patients were initially followed-up for 12 months and data from the women in the cohort was published in BJU International in 2017. For their nine-year follow-up study, the researchers analysed data from the electronic health records of their original cohort. They interviewed participants about their experience of UTIs since receiving the vaccine and asked them about side effects.

Forty-eight participants remained entirely infection free during the nine-year follow-up. The average infection-free period across the cohort was 54.7 months (four and a half years) – 56.7 months for women and 44.3 months, one year less, for men. 40% of participants reported having repeat doses of the vaccine after one or two years.

Gernot Bonkat, Professor of Urology at the Alta Uro Medical Centre for Urology in Switzerland, and the EAU Chairman of Guidelines on Urological Infections, said: “These findings are promising. Recurrent UTIs are a substantial economic burden and the overuse of antibiotic treatments can lead to antibiotic-resistant infections. This follow-up study reveals encouraging data about the long-term safety and effectiveness of the MV140 vaccine. Further research into more complex UTIs is needed, as well as research looking at different groups of patients, so we can better optimise how to use this vaccine.

“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments.”

Developed by the Spain-based pharmaceutical company Immunotek, MV140 contains four bacterial species in a suspension with water. It is available off-license in 26 countries.

Participants in the trial were all aged over 18 years and were UTI-free when they were initially offered the vaccine. None of the participants had other urinary abnormalities such as catheters, tumours or stones. The follow-up study included 72 women and 17 men and outcomes were self-reported.

Urine test halves painful procedures in bladder cancer follow up, new trial shows

A simple urine test can more than halve the number of cystoscopies necessary to follow up high-risk bladder cancer patients, new research has found.

Cystoscopies involve inserting a flexible probe through the urethra into the bladder, which allows a clinician to look at the bladder lining for signs of cancer. While they are predominantly safe procedures, cystoscopies do incur some risk of urinary infections and bleeding. They can also cause pain and discomfort.

Initial results from a two-year study, presented today [6 April 2024] at the European Association of Urology Congress in Paris, suggest that there is also no increased risk of recurrence in patients who had a urine biomarker test rather than a standard flexible cystoscopy. Full results on this aspect of the trial are expected in the summer.

The study was carried out in Denmark, where post-surgical follow up for high-risk bladder cancer recommends cystoscopies every four months for two years. In the UK, patients undergo even more frequent cystoscopies: every three months for two years.

High-risk patients with the most aggressive form of bladder cancer have a 60-70% likelihood of cancer returning within 5 years post-surgery, which is why follow up for these patients is so intensive.

The new research is the first time a urine biomarker test has been assessed in a randomised interventional controlled trial with high-risk patients. This trial design allowed the researchers to assess whether the test could reduce the number of cystoscopies patients had to undergo, as well as picking up any signs of returning cancer. Previous studies have only assessed biomarker tests observationally, adding the biomarker tests to existing standard of care.

Thomas Dreyer, a researcher at the Bladder Cancer Research Team, Dept of Urology, Aarhus University Hospital, who carried out the study for his PhD, explains: “There have been lots of studies of urine biomarker tests showing positive results, but no randomised trial to show what the impact would actually be in the clinic. We were confident the test was sensitive enough to not provide false negatives that put patients at risk. But would it provide false positives and actually result in equal or even higher numbers of cystoscopies being carried out? Our findings show that wasn’t the case.”

The researchers, from Aarhus University Hospital in Denmark, recruited 313 patients. Half were randomised to receive the standard three cystoscopies per year. The other half were randomised to receive just one cystoscopy per year, with their remaining two follow up cystoscopies replaced with the Xpert® Bladder Cancer Monitor test, a urine biomarker test. The test monitors for recurrence of bladder cancer by measuring levels of five target mRNAs, or genetic markers. The researchers chose to trial this particular biomarker test as it had previously shown promising results in high-risk bladder cancer patients.

Any patients who received a positive result on their urine test were called into hospital for a cystoscopy to check for evidence of the cancer returning. The urologists undertaking the cystoscopy were aware of the positive result, as they would be in normal practice.

After two years, for patients receiving primarily the urine test, just under 44% of follow up appointments involved a cystoscopy, compared to nearly 100% in those receiving standard treatment.

The researchers also found strong evidence that the urine test could pick up cancer recurrence before any disease was visible through the cystoscopy. For more than half of the patients who had a ‘false positive’ test – that is, the biomarker test showed positive but the cystoscopy was clear – the researchers found evidence of recurrence at a later visit.

“We know that many patients really dread their cystoscopy appointments, but are prepared to go through with them because they want to be sure they are free of the cancer,” said Thomas Dreyer. “However, if given the option of providing a urine sample instead of undergoing an uncomfortable medical procedure, most would choose that, so long as they were confident that it was just as effective.”

Joost Boormans, Professor of Urology at Erasmus University Medical Centre in Rotterdam and member of the EAU Scientific Congress Office said: “We know as urologists, we carry out too many cystoscopies, particularly during follow up of patients with non-muscle-invasive bladder cancer, so we need to find alternatives. Bladder cancer is a disease that particularly affects the elderly, and we foresee an increasing number of patients due to the ageing population, which could impact on the numbers able to access care.”

“This trial shows us a possible means of reducing cystoscopies. If the final results later this year do confirm that the urine test can pick up cancer recurrence as effectively as cystoscopies, then this is something we need to look at introducing into clinical practice as soon as possible, because it reduces demand on our resources and helps to make healthcare more accessible.”

The trial was funded by Cepheid, the company who make the Xpert® Bladder Cancer Monitor, but the trial was independently conceived and designed by the team at Aarhus University.

Five-year interval is safe for prostate cancer screening, research shows

A simple blood test every five years is sufficient to screen low risk men for prostate cancer, new research has shown.

The PSA blood test checks the level of prostate-specific antigen, a marker for prostate cancer. In Europe, only Lithuania routinely screens men for prostate cancer based on their PSA levels, as the test has historically been seen as insufficiently reliable.

The German study, presented at the European Association of Urology (EAU) Congress in Paris today [April 6, 2024], involved over 12,500 men aged between 45-50 taking part in the ongoing PROBASE trial, which is testing different prostate cancer screening protocols.

The research has also been accepted for publication in European Urology.

PROBASE is recruiting men aged 45 and splitting them into three groups based on their initial PSA test. Men with a PSA level of under 1.5 nanograms per millilitre (ng/ml) are deemed low risk and followed up with a second test after five years. Men with a PSA level between 1.5-3 ng/ml are deemed intermediate risk and followed up in two years. Those with a PSA level over 3 ng/ml are seen as high risk and given an MRI scan and biopsy.

Of over 20,000 men recruited to the trial and deemed low risk, 12,517 have now had their second PSA test at age 50. The researchers found that only 1.2% of these (146 in total) had high levels of PSA (over 3 ng/ml) and were referred for an MRI and biopsy. Only 16 of these men were subsequently found to have cancer – just 0.13% of the total cohort.

The EAU recommends that men should be offered a risk-adapted strategy (based on initial PSA level), with follow-up intervals of 2 years for those initially at risk, in which they include men with PSA over 1 ng/ml. The new findings suggest that the screening interval for those at low risk could be much longer with minimal additional risk.

Lead researcher, Professor Peter Albers, from the Department of Urology at Heinrich-Heine University Dsseldorf, explained: “By raising the bar for low risk from 1 ng/ml to 1.5, we enabled 20% more men within our cohort to have a longer gap between tests and very few contracted cancer in that time.  With nearly 14 million men aged between 45-50 in Europe, the numbers affected by such a change would be significant. Our study is still underway, and we may find that an even longer screening interval, of seven, eight or even ten years, is possible without additional risk.”

Prostate cancer screening has historically been a controversial subject, with concerns raised both around false positives leading to unnecessary invasive treatments and false negatives leading to cancers being missed. This is gradually changing due to MRI scans which can avoid unnecessary biopsies and the use of ‘active surveillance’, where men with early-stage cancer are monitored and only undergo treatment if their disease progresses.

Prostate cancer screening guidelines contradictory and unclear

Current guidelines and policies from European governments and health bodies remain contradictory and unclear, leading to high levels of opportunistic testing and inequality of access to early diagnosis, according to further research presented at the EAU Congress. The study reviewed early detection policies across the European Union and carried out focus groups with urologists to identify how guidelines were interpreted in clinical practice.

Dr Katharina Beyer, from the Department of Urology at the Erasmus MC Cancer Institute in Rotterdam, Netherlands carried out the research. She said: “Some country’s guidelines are actively against screening, others are non-committal and a few, such as Lithuania, have some form of screening. But in many countries, if you ask for a test, you can get one, sometimes free and sometimes not. This means that well-educated men, who know about PSA tests are more likely to be screened and get an early diagnosis, while others with less knowledge are at a disadvantage.”

This is also the situation in the UK, according to Professor Phillip Cornford, from Liverpool University Hospitals NHS Trust, who chairs the EAU Prostate Cancer Guidelines Committee.

Professor Cornford said: “The NICE guidelines here in the UK are incongruous. They say there’s no evidence that PSA screening is worthwhile, but at the same time say any man can ask for a PSA test if they want it. The result is that well-educated, driven men ask and others, including many Afro-Caribbean men who are actually at higher risk, don’t ask and so prostate cancers get missed.

“There is clearly a need for more organised prostate cancer screening and last November, the UK government and the charity, Prostate UK, announced a £42m research programme to look at this. The details of that should soon be made public. Each country will need to design a screening programme that fits their health system and the resources they have available. But there is still plenty we can learn from other countries and the work underway in the EU. New findings, such as those from the PROBASE trial, can help us design an appropriate screening programme both in the UK and elsewhere.”

Bladder cancer treatment can be better targeted and more effective, trials show

Testing for tumour DNA in the blood can successfully identify advanced bladder cancer patients who will not relapse following surgery, new research shows.

This could allow doctors to target treatments more effectively to those who need it, and spare those patients for whom further treatment is unnecessary, researchers say.

The findings from the screening phase of the IMvigor011 Phase III trial are presented today [Friday 5 April] at the European Association of Urology Congress in Paris.

They show that just over 90% of muscle invasive bladder cancer (MIBC) patients with a negative circulating DNA (ctDNA) test following surgery, which remained negative on follow up, did not relapse. The findings mean that use of a ctDNA test could allow some patients to be spared further treatment with minimal risk.

MIBC is an advanced form of bladder cancer, where the tumour has spread into the bladder wall. The disease is usually treated by surgery to remove the bladder. Around half of patients see cancer return, often in the lungs and usually within two-to-three years. All patients are currently offered follow-up treatment such as chemotherapy or immunotherapy to prevent recurrence, for which the side effects can be serious and lifechanging.

Other Phase III trial results, also presented at the EAU Congress today, show that patients given immunotherapy, nivolumab, as a follow up to surgery have an average survival of nearly six years, compared to four for patients on placebo.

The CheckMate 274 trial has already shown that nivolumab can reduce recurrence of disease, but these interim results are the first to show the potential benefit in overall survival for MIBC patients.

Joost Boormans, Professor of Urology at Erasmus University Medical Centre in Rotterdam, and member of the EAU Scientific Congress Office, is chairing the session where both trials will present their findings. He said:

“Although we already knew that nivolumab improved disease-free survival in MIUC patients who received radical surgery, overall survival is what really matters following local treatment, such as radical surgery. These interim findings, which show that overall survival also improves, are very encouraging, particularly as this hasn’t been the case in other recent immunotherapy trials.

“The question for regulators and healthcare authorities is whether the improvement in overall survival is enough to justify licensing or prescribing the drug for all patients, in the knowledge that some of these patients would have been cured of their cancer by surgery alone. This is where the findings from the IMvigor011 trial could really make a difference, by allowing us to select patients at highest risk who will benefit the most from treatment while sparing others for whom it isn’t needed.

“At a time when healthcare resources are under pressure, this kind of innovation is really needed.”

IMvigor011

IMvigor011 is a global, double-blind, randomised Phase III trial looking at the efficacy of the immunotherapy atezolizumab vs placebo in patients with high-risk MIBC.

The trial is recruiting MIBC patients post-surgery and testing their blood for circulating tumour DNA. Those with a positive ctDNA result are randomised to receive either atezolizumab or placebo. Those with a negative result are given no further treatment, but were followed up with scans and further ctDNA tests for up to two years. For the analysis presented at the EAU Congress today, 171 patients with a negative ctDNA test were included, with follow up continuing on a further 115.

Just 17 patients of the 171 patients (9.9%) saw their cancer return within two years. These outcomes were irrespective of the stage their tumour was at or whether it showed elevated levels of PD-L1, a protein biomarker that plays a role in cancer.

Professor Thomas Powles of Barts Cancer Institute leads the IMvigor011 trial. He said: “These results are even better than we were hoping. The risk of relapse in this ctDNA group of patients is just 1 in 10. It appears this test can effectively filter patients into two groups: those who are likely to relapse and those at much lower risk. Focusing treatment on those at risk and sparing the very low risk group potentially life-altering treatment-related side effects is attractive. Hopefully these data will allow patients to remain treatment free with the reassurance they need, that they’re unlikely to see their cancer return.”

The study is sponsored by F. Hoffmann-La Roche Ltd.

CheckMate 274

CheckMate 274 is a global, Phase III, randomised, double-blind trial of nivolumab vs placebo in high-risk MIBC after surgery.

The trial recruited just over 700 patients, with half given nivolumab and the other half given a placebo every two weeks for 12 months following an operation to remove the bladder. Patients were also tested to see if their cancer had elevated levels of the biomarker PD-L1, which nivolumab specifically targets.

The trial has already reported positive results in preventing recurrence, particularly for PD-L1 patients. Across all patients, those on nivolumab had an average of 22 months before recurrence, compared to 10 months for those on placebo. However, of the PD-L1 group, those on nivolumab had an average of over four years without recurrence, compared to just over eight months for those on placebo.

The latest results, although still early stage, show a similar benefit in overall survival. For all patients, those on nivolumab survive on average for nearly six years (69.5 months) compared to just over four years (50.1 months) for those on placebo. The researchers do not yet have enough follow-up data to separate out the PD-L1 patients, but the analysis so far shows that overall survival is likely to also be even better for this group when treated with nivolumab versus placebo.

Professor Matthew Galsky from the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, leads the CheckMate 274 trial. He said: “We know that patients with high-risk urothelial cancer are at highest risk for recurrence within the first three years after surgery. We’ve now followed a substantial subset of patients for longer than that on this study without recurrence. It looks as if the improvement in disease free survival is ultimately going to translate into improvement in overall survival. And that’s for all patients, but particularly patients with the PD-L1 biomarker. Our hope is that this improvement will then translate into an increased likelihood of curing cancer in these patients.”

The trial is funded by Bristol Myers Squibb and Ono Pharmaceutical. Dr. Matthew D. Galsky is a paid consultant to Bristol Myers Squibb.

Mental health costs of lockdown compliance still being felt, research shows

The more strictly people complied with Covid restrictions during the pandemic, the worse their mental health today, new research has found.

The analysis by researchers from Bangor University looked at the behaviour of around 1700 people during the Covid restrictions in relation to their personality traits and their post-pandemic recovery. The study aimed to answer three broad questions: who follows health advice, what can be done to improve compliance; and what are the costs for those who comply?

The team found that those who were more sensitive to the needs of others were more likely to have complied with lockdown rules and health advice, compared to those who were more focused on their own needs and priorities.

However, they also found that those who reported high levels of compliance with Covid restrictions and were most worried about infection during the pandemic are least likely to have resumed normal behaviour and more likely to be experiencing stress, anxiety and depression now.

Dr Marley Willegers, from the Institute for the Psychology of Elite Performance (IPEP) at Bangor University, said: “There was naturally a lot of focus on getting public health messages out when Covid first emerged, to change people’s behaviour. Similarly, throughout the pandemic, messaging campaigns were designed to ensure people continued to follow the rules. But there was no messaging campaign as we came out of the pandemic to help everyone safely transition back to normality. Without this, certain personality types have retained infection prevention behaviour and anxiety that undermines their mental wellbeing.”

The study involved over 1700 people, recruited through Healthwise Wales, who were asked earlier this year to answer questions about their personality traits and their attitudes to Covid and behaviour during the first lockdown (March-September 2020). The researchers also questioned 230 people who were friends or family of those involved in the study, to cross check respondents’ recollections of their behaviour with others who knew them well.

The team followed up with 850 of those who’d taken part, asking them to report their levels of well-being, stress, anxiety, depression and infection prevention every two weeks over a three-month period between February and May 2023.

They categorised each person in relation to two types of personality trait – those who are more focused on what affects them (agentic personalities) and those who are more focused on what affects others (communal personalities). In general, the former were less likely to have complied with Covid rules, except where they felt under personal threat of infection. Conversely, communal personalities were less likely to improve their compliance with health advice as the threat of infection increased, possibly due to them taking personal risks to help others.

The researchers found, regardless of personality, higher levels of compliance with Covid rules during the pandemic (March-September 2020) predicted lower current levels of well-being (Feb-March 2023). In other words, the more people complied with Covid rules during the pandemic, the worse their wellbeing emerged in the aftermath.  

Dr Willegers said: “It’s clear from our research that if government advertising campaigns want to change the public’s behaviour, they need to take both personality types into account. Campaigns need to highlight the personal costs and benefits involved not just people’s responsibility to others.”

One example the researchers point to is the introduction of the 20mph limit in Wales. The existing campaign to inform the public of the speed limit change, which focuses primarily on the lives potentially saved by driving slower is unlikely to encourage compliance from more agentic personalities. A broader campaign, which also focuses on personal costs and benefits of compliance with the change would target a wider range of personality types more effectively, the researchers say.

The full report ‘The effect of agency and communion on pandemic response and post-lockdown recovery’ is published by Bangor University

Research significantly reduces HIV-linked meningitis deaths in African hospitals

A research project studying how best to implement ‘back to basics’ clinical and laboratory care in public hospitals in three African countries has halved the number of deaths from HIV-linked meningitis. The results are reported in The Lancet HIV today.

A joint European and African research partnership, the DREAMM project worked with local health leaders and healthcare workers, empowering them to design and implement changes to routine care for patients with HIV-related central nervous system conditions: cryptococcal meningitis, tuberculous meningitis, bacterial meningitis and cerebral toxoplasmosis.

DREAMM (Driving Reduced AIDS-associated Meningo-encephalitis Mortality) was funded by the European and Developing Countries Clinical Trials Partnership and by ANRS – IED (ANRS Emerging Infectious Diseases).

The DREAMM project aimed to ensure that all HIV patients with symptoms of meningitis or cerebral toxoplasmosis were diagnosed and treated rapidly and effectively.

Despite the roll-out of antiretroviral therapy, there are still over half a million HIV-related deaths annually in Africa, of which a third are caused by conditions like meningitis that attack the central nervous system. These conditions should be treatable, but lack of diagnosis, the correct drugs and training on how to use these safely mean that many are fatal.

The project consortium researchers worked with the local Ministries of Health and empowered local health leaders, including hospital staff, to put in place rapid diagnostic testing and to ensure that the WHO cryptococcal meningitis treatment guidelines for confirmed cases were followed. Diagnosis involved both bedside point-of-care tests carried out by clinical staff and more detailed laboratory tests.

The project was led by Dr Angela Loyse, a global health expert based at St George’s, University of London, and African health researchers (Drs Cecilia Kanyama, Charles Kouanfack, Saulos Nyirenda & Prof Sayoki Mfinanga). It involved public hospitals in Malawi (Lilongwe and Zomba), Tanzania (Dar es Salaam) and Cameroon (Yaoundé). From Institut Pasteur, Professor Olivier Lortholary (Necker Pasteur Center for Infectious Diseases and Tropical Medicine) was the ‘Principal Investigator Nord’ for the DREAMM Cameroon site, while Research Engineer Aude Sturny-Leclere developed and led the delivery of the DREAMM laboratory training programme.

Dr Loyse said: “By performing diagnostic tests such as lumbar punctures, on admission, the hospitals could get a rapid diagnosis, and then start treatment while the patient was still in the emergency area. This meant that ward care could become more about monitoring than chasing diagnostics. We also had in-parallel lab testing for quality control and to determine diagnoses not immediately clear by the bedside.”

Local healthcare leaders provided training – with support from the St George’s and Institut Pasteur teams – for both frontline healthcare workers and laboratory technicians. The team set up ‘communities of practice’ in each hospital, so experience could be shared between staff and ongoing support provided from healthcare leaders. Virtual ward rounds enabled doctors to discuss difficult cases with a mentorship community of senior doctors, laboratory experts and researchers online.

Dr Cecilia Kanyama, an expert on HIV-related conditions, led the project in Lilongwe, Malawi. She said: “It was really encouraging to see the local leadership so involved and keen to take this on, particularly around the point of care testing. We were just facilitating, but there was excellent involvement of local key players, nurses and clinicians. That is really important to make this kind of intervention sustainable.”

Before the training was provided and the new procedures put in place, the team followed the progress of patients presenting at the hospitals with symptoms of HIV-related meningitis, and found that within two weeks of admission to hospital, nearly half (49%) of these patients had died.

The new, co-designed procedures for dealing with HIV-related meningitis and cerebral toxoplasmosis were put into practice at each site for around 10 months, between January 2018 and March 2021.

The project recruited a total of 365 adults living with HIV who were admitted to hospital with a suspected first episode of CNS infection. Just under a quarter of these patients died (24%) within two weeks of admission, half the rate before the new procedures were put in place.

The researchers are now calling for the project to be urgently scaled up to reduce unnecessary deaths from HIV-related central nervous system infections. This is echoed by African health leaders on the ground.

Dr Kanyama said: “Accessibility to point of care testing is really crucial and every hospital in Malawi should have it. Similarly with medication; tertiary level hospitals have it, but the district hospitals typically won’t. We still have a very long way to go, but we’ve seen what is possible if these resources are made available.”

Dr Loyse added: “We’ve shown that optimising the pathways for diagnosis and treatment of HIV-related central nervous system infections has a high potential to save lives, and that this is feasible in resource-limited settings. Access to essential tests and medicines in public facilities needs to be urgently ensured.”

‘Reduction in mortality from HIV-related central nervous system infections in routine care in Africa (DREAMM): A before-and after- implementation study’ is published today in The Lancet HIV.

Government reneging on food policy plans, say experts

A year after publication of the UK’s 2022 Food Strategy, the Government has abandoned promises to transform the national food system and crucial targets on health, climate and nature will be difficult to meet, a group of eminent food system experts warn.

Writing in Nature Food, five academics from the Universities of York, Sheffield, Reading and Cambridge argue that the Government’s U-turns and lack of ambition on food policy leave the nation increasingly vulnerable to rising food prices, diet-related health conditions, and a decline in biodiversity.

The academics call on the UK’s next government to develop a more coherent, coordinated and collaborative approach to food policy. They propose a new five-point plan to support the UK to transition towards a more sustainable, healthier food system.

The Government’s wide-ranging 2022 Food Strategy focused on long-term measures to support a resilient, healthier, more affordable and sustainable food supply. It was a response to the recommendations set out in the previous year’s National Food Strategy Independent Review, authored by Henry Dimbleby.

In their commentary, the academics note that there have been a series of shelved government policies and reversed decisions since the 2022 Food Strategy was published, despite what they see as a collective will for change across the UK agri-food sector.

Grounded in recommendations from the Dimbleby Review, as well as evidence from several UK Government funded policy research programmes, the five-point plan proposes:

• Setting up a cross-government commission that joins up population and planetary health to make policy decisions about future systems.

• A full economic analysis of the recommendations evidenced in Dimbleby’s review.

• Free school meals made available to all primary school children in England, revolutionising catering in schools.

• Integrating mandatory health and environmental metrics into the Food Data Transparency Partnership. This partnership promotes the use of data when making decisions about the production and sale of healthier and more sustainable food and drink.

• A comprehensive framework for how land should be used for food production, which would help to reverse the UK’s status as the worst-performing G7 country in terms of species depletion.

Lead author Professor Bob Doherty, Dean of the School for Business and Society at the University of York, said: “Although the Government’s 2022 Food Strategy was not as robust as the Dimbleby Review, it was a critical step in the right direction. Just one year later, Government have reneged on their responsibility to implement change across the whole agri-food sector. We are now seeing a gradual decline in food security, diet, soil health and biodiversity. To prevent the UK falling further behind other G7 nations, we need action to tackle diet-related health, improve school meals for the 800,000 children in poverty, increase the consumption of fibre, fruit and vegetables, and to better measure the environmental impacts of food production so the UN goals on Net Zero greenhouse gas emissions can be met.

“Rather than stalling and making U-turns, if the UK Government implemented their own food strategy it would boost our agri-food sector and save the country a lot of money in terms of GDP, as well as improve the health of soil and make a valuable and long-term contribution to human and planetary health.”

Benchtop NMR spectroscopy can accurately analyse pyrolysis oils

A team of researchers at Aston University has demonstrated that benchtop spectrometers are capable of analysing pyrolysis bio-oils just as well as far more expensive, high-field spectrometers.

Bio-oils resulting from the intense heating (pyrolysis) of industrial or agricultural by-products, are increasingly seen as potential alternatives to fossil fuels. But the stability and consequent treatment of these bio-oils depends entirely on their composition; and since they are often mixtures of many dozens, or hundreds, of different compounds, analysing such complex mixtures is not simple – or cheap.

Dr Robert Evans, Senior Lecturer in Physical Chemistry at Aston University, explains: “The composition of any pyrolysis bio-oil is absolutely key to future use. For example if there are oxygen-containing chemicals in the oil, that will make the oil more corrosive and it will be more unstable. So in particular we need to know if carbonyl groups are present – where oxygen and carbon atoms are bonded together – as these can have a major impact.”

A leading method of analysis is high-field nuclear magnetic resonance (NMR) spectroscopy, which gives a detailed breakdown of the identity and concentration of chemical species present in any sample. However these large high-field NMR spectrometry machines cost in the range of £600,000-£10million and require a supply of expensive cryogens and solvents, so are generally only found in the very biggest research facilities.

The team at Aston, led by Dr Evans, set out to see if ‘low-field’, or benchtop, NMR spectrometers, could analyse pyrolysis oils well enough to produce the necessary detailed information. Benchtop NMR spectrometers use permanent magnets, which don’t require cryogenic cooling, so cost much less to purchase and maintain. However, using lower strength magnets comes at the cost of lower sensitivity and poorer resolution. While they can find some use as research instruments, they are also commonly found in teaching laboratories.

The study, carried out with collaborators at the University of Tennessee, tested pyrolysis oils produced from a number of different plants, and compared the results from benchtop spectrometers to both high-field spectrometers and other methods of analysis. They found that the benchtop machine estimates compared favourably with titration analysis for overall carbonyl content, as well as matching high-field spectrometry for the specific identification of carbonyl groups such as ketones, aldehydes and quinones.

Dr Evans said: “Despite the known limitations of benchtop spectrometers, a very similar quality of NMR data could be obtained for these samples, enough to accurately estimate concentrations of different classes of carbonyl-containing species. Using benchtop spectrometers will make NMR analysis of pyrolysis oils much simpler, cheaper, and more accessible to a wider range of different users.”

Quantitative Low-Field 19F NMR Analysis of Carbonyl Groups in Pyrolysis Oils is published online today in ChemSusChem, a journal of Chemistry Europe.

ChatGPT could free doctors to spend more time with patients

Artificial intelligence could be used to free up hospital doctors and surgeons from repetitive paperwork so they can spend more time with patients, according to a new trial.

Doctors have used the online AI programme ChatGPT to write detailed surgical discharge letters that give information to patients and their GP about their care after procedures.

The AI-written letters were deemed to be almost indistinguishable, and in some cases were classed as better in terms of the medical information they contained, than real hospital letters written by humans.

It raises the potential for discharge letters, which NHS doctors tend to write out individually for each patient in many hospitals, to be automatically generated using AI.

The study is being presented today (12 July 2023) at the first ever Health and Care Analytics Conference, which is taking place in Birmingham on 11-12 July.

Dr Chris Bodimeade, a Core Surgical Trainee in South East England, who led the work, said: “I am half way through my core surgical training and one of the frustrations I have with the NHS is the amount of time I have to spend on a computer.

“Doctors are increasingly becoming tethered to a computer doing mundane and repetitive paperwork tasks rather than spending time with patients. But at the same time I’ve been excited by the development of AI technologies like ChatGPT, so I wondered if there was a way of using it to make some of these tasks easier.”

Surgical discharge letters for routine operations usually contain a summary of the treatment a patient has received during their stay in hospital, alongside any potential complications and how their care should be managed after they leave hospital.

Dr Bodimeade decided to ask ChatGPT to write a surgical discharge letter for two hypothetical patients who had undergone an elective tonsillectomy. To generate the letters, he gave the AI chatbot the simple instruction: “Please write a hospital discharge letter for patient undergone a tonsillectomy.” No patient information was included.

He then showed the resulting letters to 19 other consultants and doctors at his current hospital alongside two real letters written for patients that had been anonymised. The doctors and surgeons found the letters indistinguishable and one of the letters was on average rated to contain better medical information and was easier to read than the real discharge letters.

Dr Bodimeade said that while his study was small, he hopes it might lead to greater exploration of how artificial intelligence might lighten the workload of NHS staff.

He stressed that any letters would all still need to be checked by a doctor before being sent and said colleagues in other surgical departments were already conducting their own experiments to use ChatGPT to write discharge letters.

He said: “I’m hoping this work can open up a discussion about how technology that is freely available can be used within the confines of confidentiality and patient safety to make our jobs much more efficient and improve a service that is under tremendous stress.”

Machine learning helps manage demand for emergency beds

New machine learning technology can use real-time A&E data to predict how many patients will need an emergency bed later that day, in which part of the hospital.

The technology is being presented today (11 July 2023) at the inaugural Health and Care Analytics (HACA) conference.

The tool was developed by a team of analysts and hospital staff at UCL and UCLH. It is now being used by operational staff at UCLH to forecast how many emergency beds will be needed within the next eight hours, and where: surgical, medical, haematology and oncology, or paediatric departments. Early tests suggest the tool is better at predicting bed demand than standard methods.

Many UK hospitals are currently operating at capacity, which means planned surgeries can be cancelled last-minute if the demand for emergency beds is high. By predicting short-term fluctuations in capacity across the hospital, the tool can help operational staff ensure there are enough beds in each department to minimise impact on patients.

Dr Zella King (Clinical Operational Research Unit at UCL), who co-developed the technology, said: “Our research demonstrates the potential of machine learning and data in the day-to-day operation of hospitals by looking for patterns in real-time patient data and supporting hospital staff to plan accordingly. Hospital capacity is affected by many systemic factors and we’re not suggesting machine learning is a magic bullet to fix this complex challenge. But it’s fantastic that our tool is making a meaningful difference to the day-to-day running of UCLH.”

Co-author Craig Wood (Clinical Operations Manager at University College London Hospitals NHS Foundation Trust (UCLH)) said: “Managing the flow of patients around the hospital is the continuous, careful balance of patients who are in for elective treatment with people in A&E who need a bed as an emergency. Since implementing the tool at UCLH, we’ve been able to make targeted actions to free up beds in specific areas of the hospital, improving our ability to manage hospital capacity.”

As patients move through A&E, the machine learning tool incorporates additional data – like vital signs, blood test results and whether a patient is to be examined by specialist doctors – and updates its forecast every 30 minutes. It also predicts how many people will enter the emergency department and need a bed within 8 hours, assuming the A&E department is meeting its targets for wait times. The team trained the tool to do this using electronic health records from more than 166,000 patients who visited A&E between August 2021 and August 2022.

“Machine learning could be a powerful tool to support hospital operational staff, but its outputs have to be both actionable and aspirational,” said Dr King. “At HACA, we’re sharing what we’ve learned from working as a close team of analysts and hospital staff. We hope our insights will be helpful for others thinking about adopting similar approaches at their hospitals.”

The research builds on the team’s previous work, published in the open access journal npj Digital Medicine in 2022, when the tool could predict the total number of emergency beds needed in the next 8 hours, but couldn’t yet break this number down by department.

Mental health of children suffered during pandemic

The scale of the mental health crisis among children during the Covid-19 pandemic has been revealed by new analysis of NHS data.

Prescriptions for mental health conditions among children in the north-east of Scotland were 59% higher in 2021 compared to six years earlier, according to the research. Prescriptions rose by 24% between 2020 and 2021 alone.

Referrals of children to see outpatient mental health specialists increased by 9% between 2015 and 2021, but rose steeply since the pandemic. The most pronounced rise in referrals was among teenage girls which were 35% higher in 2021.

The results are due to be presented at the first ever Health and Care Analytics Conference, which is taking place in Birmingham on 11-12 July.

While the study examined data from mental health services for children aged 2-17 years old in the Grampian region of NHS Scotland, the researchers say the findings reflect similar trends in other parts of the UK.

“There has been a lot of concern about children’s wellbeing post-pandemic and the data does seem to reflect this,” said Dr Jessica Butler, Lead Data Scientist for NHS Grampian and a Senior Research Fellow at the University of Aberdeen, who led the study.

“The rate of referrals of children to specialists was steady pre-pandemic, but we see a rise post-lockdown. It’s clear that it is steepest among the older children, and particularly older girls, where we see the biggest rise in referrals.”

The research also highlighted other differences between the sexes, ages and residential areas. For example, the rate of prescribing and referrals to specialists in the most deprived areas was double that in the least deprived. Prescriptions of mental health drugs to boys were twice as high as those for girls, with the majority of the drugs being given to young boys to treat ADHD. The prescription rate to girls, however, rose steeply after puberty, mainly to treat depression.

The study highlights just how useful information within NHS databases can be to identify potential changes in patient need and help health services allocate resources, but also reveals its limitations.

Dr Butler and her team were able to examine anonymised data contained within NHS Scotland databases in the Grampian region for their research. But they said this only reflects one side of those dealing with children who are struggling with their mental health. Local authorities, social workers, teachers and police will also support children.

Butler and her team have created software that is freely available to allow other NHS services to carry out their own analysis.

The research was conducted as part of a project by the Health Foundation’s Networked Data Lab examining children and young people’s mental health in England, Scotland and Wales. Five teams around the country used anonymised, high security data held in their local NHS databases.

The full research being presented at the conference was published earlier this year in BMC Psychiatry: https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-04438-5

NHS geospatial app saves vital staff time

NHS Trusts could help staff plan their journeys more efficiently and cut their impact on the climate with software that can help district nurses and health visitors plan their journeys more efficiently.

Data scientists from NHS England’s Digital Analytics & Research Team and engineers from Google Health collaborated to develop a web app that can optimise routes between locations. This can help to reduce the amount of fuel used when making health visits or by ambulances that have a series of patient drop offs to do. As well as saving money and cutting carbon emissions, it can also mean health workers spend less time travelling between visits, giving them more time to spend with patients.

It is due to be presented at the first ever Health and Care Analytics Conference, which is taking place in Birmingham on 11-12 July.

“District nurses can be visiting multiple patients in their homes each day, so we wanted to find a way for them to plan the most efficient route to get to the patients,” said Paul Carroll, senior data scientist at NHS England’s Digital Analytics Research Team, who led the project.

“If they have 10 appointments in a day, there could be 3.6 million different routes they could take. If there are 12 addresses to visit, that becomes 479 million permutations. These are difficult problems to solve and we wanted to be able to do it in a way that could be done an average laptop computer.”

Currently, many NHS trusts rely on third party companies to provide routing information.

Mr Carroll and his team, who were working as part of programming community called NHS-pycom, developed the code in an open-source app framework called Streamlit so that analysts at NHS trusts could adapt it to their requirements. This could help to overcome potential data privacy issues as the patient information would not have to be sent to a third party or uploaded to a server.

In the case of district nurses, they could use the app to plot routes between up to 12 addresses and display them on a map, taking into account the distance between each one, driving times at peak and off-peak hours, walking time and cycling time.

“The idea is they can spend less time travelling and more time with patients,” said Mr Carroll.

The app has two additional functions which were developed in response to unmet needs identified by NHS Trusts. One suggests the shortest route that staff and patients might be able to take to reach a hospital or other health service. This could be used to help reduce the climate emissions as they travel to work or to help patients find which service is closest to them. Although this initially used driving and walking data, Mr Carroll said it could be expanded in the future to include public transport and cycle routes.

The second tool was designed to show the best location for services such as a vaccination centre or mobile blood test unit to ensure they can cover as much of the population in an area as possible. This took into account travel time and local authority population data and was a simplified version of something that many retailers already use to find the best place to locate a new store that is accessible by as many people as possible and away from competitors.

“Geospatial needs within the NHS are everywhere, from ambulance patient drop-offs to where to site a new GP practice within your community,” said Mr Carroll.

Multiple factors delay timely endometriosis diagnosis, study shows

New research from Aston University has uncovered reasons why endometriosis, one of the most common and debilitating gynaecological conditions, takes an average of 8 years to be diagnosed by medical professionals.

Reviewing qualitative studies from the past 20 years, the researchers found a range of contributing factors including: a continuing stigma around periods; society’s normalisation of menstrual pain; and a lack of medical training about the condition.

Endometriosis, which affects 10% of women globally and 1.5 million women in the UK alone, is caused by endometrial (womb) tissue growing outside the womb. It’s extremely painful, exhausting, interferes with daily life and can lead to infertility if untreated.

The researchers found that women in the studies often weren’t sure if their pain was unusual or severe enough to seek treatment. When they did, some found that their GP was doubtful, or even dismissive of their symptoms. GPs in two of the studies themselves admitted that they found it difficult to differentiate problematic pain from ordinary menstrual symptoms.

Dr Sophie Davenport, who led the research and is now working as a doctor in the NHS, says: “Society has traditionally normalised period pain, so we need to rethink what constitutes ‘non-normal’ periods. If symptoms are affecting daily life, where the woman is not going to work or school, or unable to carry on a social life, that’s a clear sign that medical intervention is needed”.

Many GPs in the studies reviewed mentioned a lack of knowledge about endometriosis, with some saying they’d had scant training in medical school about it. Endometriosis symptoms can vary widely and overlap with other common conditions, so the signs can be difficult to spot.

Dr Davenport says: “Given the numbers of women affected, we think there should be additional, mandatory training about menstrual conditions during medical school. At present, as little as 4 weeks out of 5 years of medical training may be spent on gynaecology; and during that time, endometriosis may barely be mentioned. Given that 1.5 million women in the UK are affected, we think it’s time to prioritise this.”

Even if suspected, the definitive method of diagnosis has been by laparoscopy under general anaesthetic, so some practitioners have been reluctant to order such an invasive procedure. However recent ESHRE guidelines now recommend a two-step approach in which treatment is started more quickly, based on clinical suspicion and MRI/ultrasound imaging, rather than waiting for laparoscopic findings. Supervising author Dr Dan Green, Senior Teaching Fellow at Aston University’s College of Health and Life Sciences, adds: “It will be interesting to see if these new ESHRE guidelines affect the existing time to diagnosis, and can improve patients’ experiences in future.”

Emma Cox, CEO of Endometriosis UK, comments: “We hear many stories at Endometriosis UK evidencing the points this research highlights. The study underlines once more that those with suspected and diagnosed endometriosis are being consistently let down. I urge Government to use these findings to drive forward real action towards ensuring greater, faster and easier access to medical professionals with a specialist interest in endometriosis across England, Scotland, Wales and Northern Ireland.”

She continues: “It’s important that women experiencing chronic pelvic pain or other symptoms of endometriosis speak to their GP, and when they do they should expect to be listened to, believed and understood. We have heard many stories of such symptoms being shrugged off as ‘normal’, ‘not serious’ or ‘just part of being a woman’. These attitudes are changing, but sadly we still have some way to go.”

‘Barriers to a Timely Diagnosis of Endometriosis: A Systematic Review and Qualitative Synthesis’ will be published in ‘Obstetrics & Gynaecology’ on July 6 2023.

Improve reading skills to help transition to secondary school, says report

Reading skills are critical for children to succeed at school, but many are not getting the targeted support they need, new research has found.

The Reading and Vocabulary project, by researchers from Aston University and Royal Holloway, University of London, found that about one in five children enter secondary school with their reading or vocabulary skills two years or more behind expected levels.

The findings, and recommendations based on them, are published today in a report funded by the Nuffield Foundation.

Weaknesses in reading proficiency, vocabulary or comprehension each require different types of support, but tests typically used in school fail to differentiate between them.

The researchers say that increased monitoring and more targeted support for reading and vocabulary are needed in upper primary and secondary schools.

They also call for better continuity between primary and secondary school basic skills curricula to help students make a successful transition.

The Reading and Vocabulary project tracked 598 children from age 10-13, testing their reading skills at five points during their transition from primary to secondary school and over the following summer holidays. The study involved children from 16 primary schools and 53 secondary schools in Birmingham, just over half of whom were girls.

The team looked at whether the summer between primary and secondary schools was any different to other summers in terms of children’s development in reading and vocabulary.

Secondary school teachers often report that children’s attainment in their first year is below what would be expected from their national curriculum test (SATs) results in year 6. This has led to the theory of a slump in attainment during the transition from primary to secondary school.

In fact, the Reading and Vocabulary project found that children’s development followed a similar pattern in all summers. Children continued to learn everyday vocabulary at the same rate all year round (words like adjustable, citrus, foundation), but their learning of specialist vocabulary linked to the curriculum slowed down each summer, compared to during the school year (words like hibernate, periscope, translucent).

Study lead, Dr Laura Shapiro, reader in the School of Psychology at Aston University, said: “Our results show that the issue is not a slump in attainment, but a jump in expectations. In secondary school, students need to learn a wide range of vocabulary, across different subject areas taught by specialist teachers. If students don’t have the reading proficiency to learn in this new environment, then that presents a barrier to accessing the secondary curriculum. Closer coordination between primary and secondary schools, such as a basic skills curriculum that continues through the transition, could help to mitigate this.”

As part of the Reading and Vocabulary project, the team tracked the books children were reading in their leisure time, and the number of times they encountered particular words (e.g., “tempest”, “courtroom”, “rogue”). They found a direct relationship between the number of times children read a word, and their ability to understand and remember it. This shows how important leisure reading is for vocabulary learning. The team also found that children who were more proficient at reading were more inclined to read in their leisure time. More proficient readers also found it easier to learn new words.

Study co-lead from Royal Holloway, University of London, Professor Jessie Ricketts said: “The connection between reading proficiency and learning new words might seem obvious, but this is the first time this has been demonstrated in a real-life context. We show that, if we can help children to read more proficiently, then other benefits are likely to follow, such as better learning of new vocabulary and more time spent reading. Similarly, if reading proficiency is low, then children are going to be struggling to learn new words, which will disadvantage them in the transition to secondary school.”

The team recommends that reading skills continue to be monitored during secondary school so that children’s needs can be addressed with targeted support and interventions. They also recommend a two-step process with initial screening using broad group-level tests to identify children with difficulties. These children can then be given diagnostic assessments that pinpoint the nature of their reading needs, such as lack of fluency, difficulty decoding words, challenges with reading comprehension or a limited vocabulary.

Ruth Maisy, Programme Head of Education at the Nuffield Foundation said “Time spent reading improves children’s vocabulary and understanding. So, it is clearly important to encourage children to read for pleasure. We hope this work will assure teachers and parents that anything they can do to encourage a love of reading will be time well spent.”

Ovarian cancer study identifies key genes for potential treatments

New research is increasing our understanding about why some women with the most lethal form of ovarian cancer respond much better to treatment than others.

Researchers at Imperial College London have confirmed that the tumours of some women with high-grade serious ovarian cancer (HGSOC) contain a type of lymphoid tissue – known as tertiary lymphoid structures, or TLS – and that the presence of this tissue gives women a significantly better prognosis. They have also identified genes in HGSOC that are important for TLS formation and function.

The lymphatic system in our bodies helps fight off infection by producing immune cells such as T cells and antibodies. But TLS, which are in some ways similar to ‘normal’ lymphatic tissues, are being found by researchers in different types of tumours.

By analysing tumours from 242 HGSOC patients before treatment and comparing them to progression free survival rates, the researchers found that women that had TLS in their tumours had a significantly better outcome. The study, published in Cell Reports Medicine and funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre, is one of the first times scientists have found TLS in women with high grade serious ovarian cancer and linked them to a better outcome.

Lead researcher Dr Haonan Lu, from the Department of Surgery and Cancer, said:

“People tend to think of all cancer cell activity as purely malignant – but the reality is less clear-cut. Tumours can hijack a number of normal body processes and here, they seem to be hijacking the formation of normal human lymph tissue within themselves. Some of these lymphoid structures are able to then mature and activate T cells, which could attack the cancer itself.”

Approximately 7,500 women are diagnosed with HGSOC each year, and because it is often discovered late, many patients experience disease relapse, leading to a five-year survival rate of below 40 per cent. It’s presently treated with surgery and chemotherapy.

The team was able to pinpoint the relevant genetic mutations involved in the cancer’s TLS formation, some of which are known to have immune-suppressing functions. The researchers found that copy mutations in the genes IL15 and CXCL10 in HGSOC can inhibit the lymphoid tissue forming. They also found that another set of genes, DCAF15, plays a role in interacting with the TLS tissues after they have been formed, probably making them more or less active.

Dr Lu said: “There is great potential for targeting these genes for benefits in ovarian cancer treatment. It’s now becoming clear how the genetic background of the tumour type interacts with a TLS to have more or less TLS function, and that will help us identify potential targets for therapy.”

The researchers have also, for the very first time, developed a potential method of identifying patients with high levels of TLS from standard CT scans, using artificial intelligence. This could ensure that those women who would benefit from different treatments are found more quickly.

Although CT scans form part of standard treatment of the condition, TLS tissues are not visible to the human eye from a normal CT scan. But the research team has developed an artificial intelligence algorithm that was trained to detect the structures within the tumours and have successfully tested the algorithm on scans of patients at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, known to have TLS tissues.

Professor Eric Aboagye, Professor of Cancer Pharmacology & Molecular Imaging at Imperial College London, said: “This non-invasive identification test means that oncologists will be able to determine if a patient has high or low TLS in future and treat them accordingly.”

The researchers have now received a project grant from Target Ovarian Cancer to further investigate the relevant genetic mutations identified, and explore whether it’s possible to activate anti-tumour immunity for all HGSOC patients, even those without TLS in tumours.

World’s first picture of the molecular machinery that makes cilia beat

The first picture of the structures that power human cilia – the tiny, hairlike projections that line our airways – has been produced by a team involving UCL researchers. The information revealed could lead to much-needed treatments for people with rare cilial diseases.

The study, published in Nature on, combined advanced microscopy and artificial intelligence techniques to create a detailed snapshot of the structure of human cilia. These are the microscopic projections on the cells that line our lungs, ears and sinuses and beat rhythmically to keep the lungs clear from mucus and bacteria. People who inherit the rare condition primary ciliary dyskinesia (PCD) have defective cilia that can’t effectively remove debris from the airways, and so suffer from breathing difficulties and chronic lung infections.

For the first time, the scientists visualised the molecular ‘nano-machinery’ that causes cilia to beat, visible as identical structures dotted every 96 nanometres along the cilia length. These structures come together to form the axoneme. In healthy airways, this complex structure is tightly controlled, with molecules precisely arranged to make cilia beat in a rhythmic, wave-like motion, around a million times a day.

In people with PCD, the team found that cilia don’t beat correctly because key elements of the axoneme structure are missing, caused by genetic mutations. This new information could lead to new medicines that target these defects, making cilia beat properly.

Study co-author, Professor Hannah Mitchison (UCL Great Ormond Street Institute of Child Health), said: “Treatments for PCD currently work to clear people’s airways and prevent infection. Our findings offer the possibility of molecular medicines to precisely target tiny defects in the axoneme and make cilia beat as they should.

“Molecular medicines are showing promise for other rare diseases, and COVID-19 research has unlocked new ways to deliver these drugs directly to the lung. If we can combine these advances with our new findings, my hope is that we’ll bring molecular medicines to people with PCD within the next 5 to 10 years.”

The team’s research could also prove useful for infertility, as sperm cells rely on a similar axoneme structure in their tails to propel themselves forward.

The research team was a global collaboration, with scientists based across the UK, US, Netherlands, China and Egypt. “It can be difficult to study rare diseases like PCD, because patients are spread thinly across the world. In the UK, we think around 9,000 families may be affected by PCD,” said Professor Mitchison. “Our study was made possible by a fantastic international collaboration between clinical scientists, biologists and members of the rare disease community willing to take part in our research.”

In addition to human cilia, the team examined the axoneme structure of a single-celled alga called Chlamydomonas reinhardtii, which uses two tail-like projections on its surface to swim. Despite being separated by more than 1 billion years of evolution, the alga’s tails shared structural similarities with the human airway cilia, highlighting the importance of the axoneme throughout evolution.

This study involved collaborators at Harvard Medical School, Alexandria University, University of Leicester, Amsterdam University Medical Centers, Guy’s and St Thomas’ NHS Foundation Trust and Imperial College London.

At UCL, the study was supported by NIHR Great Ormond Street Hospital Biomedical Research Centre, the Ministry of Higher Education in Egypt and a MRC UCL Confidence in Concept grant.

Urine gene test can predict bladder cancer years before diagnosis

Testing for genetic mutations in urine can detect bladder cancer years before the disease shows clinical symptoms, new research has shown.

The study, by researchers from France, Iran and the United States, identified mutations across ten genes that were able to predict the most common type of bladder cancer up to 12 years in advance of diagnosis.

The findings are presented today at the European Association of Urology (EAU) annual Congress in Milan.

Bladder cancer is not a rare disease – it is one of the top ten most common cancers in the UK and the fifth most common in the European Union, with over 200,000 cases in the EU each year. Only around half of those diagnosed with the advanced disease will survive more than five years, mainly due to late diagnosis and recurrence of the disease. By contrast, if their cancer is detected at early stage, more than 80% of patients survive for at least five years.

Lead researcher Dr Florence Le Calvez-Kelm, from the International Agency for Research on Cancer (IARC) in Lyon, said: “Diagnosis of bladder cancer relies on expensive and invasive procedures such as cystoscopy, which involves inserting a camera into the bladder. Having a simpler urine test that could accurately diagnose and even predict the likelihood of cancer years in advance could help to spot more cancers at an early stage and avoid unnecessary cystoscopies in healthy patients.”

The study was based on the UroAmp test, a general urine test that identifies mutations in 60 genes, developed by the Oregon Health Science University spin out company, Convergent Genomics. Drawing on previous research to identify genetic mutations linked to bladder cancer, the research team narrowed the new test down to focus on mutations within just ten genes.

Working with colleagues from the Tehran University of Medical Sciences in Iran, they trialled the potential new test using samples from the Golestan Cohort Study, which has tracked the health of more than 50,000 participants over ten years, all of whom provided urine samples at recruitment. Forty people within the study developed bladder cancer during that decade, and the team were able to test urine samples from twenty-nine of them, along with samples from 98 other similar participants as controls.

Of the 29 participants who’d developed bladder cancer within the Golestan cohort, the test was able to accurately predict future bladder cancer in 19 (66%) of them, even though urine samples had been taken up to 12 years before clinical diagnosis. Fourteen of these participants were diagnosed with bladder cancer within seven years of urine collection, and the test was able to predict cancer in 12 (86%) of these. The test was accurately negative in 94 of the 98 participants (96%) who would not develop cancer in the future. Among those where the test was negative but who did eventually develop bladder cancer, no cancer was diagnosed until at least six years after the urine collection.

The test was also trialled with colleagues from Massachusetts General Hospital and Ohio State University using samples from 70 bladder cancer patients and 96 controls, taken prior to a cystoscopy. In contrast with the Golestan study, some of these samples were provided by cancer patients on the day they were diagnosed, rather than many years before.

Mutations were found in urine samples from 50 of the 70 patients (71%) whose tumours were visible during the cystoscopy. Some of these were new diagnoses and others involved a cancer recurring. Mutations were not found in 90 of the 96 (94%) patients with a negative cystoscopy.

Dr Le Calvez-Kelm believes these results demonstrate the potential of a genetic urine test for early detection of bladder cancer. She said: “We’ve clearly identified which are the most important acquired genetic mutations that can significantly increase the risk of cancer developing within ten years. Our results were consistent across two very different groups – those with known risk factors undergoing cystoscopy and individuals who were assumed to be healthy.

“Should the results be replicated in larger cohorts, urine tests for these mutations could enable routine screening for high-risk groups, such as smokers or those exposed to known bladder carcinogens through their work.

“This kind of test could also be used when patients come to their doctors with blood in the urine, to help reduce unnecessary cystoscopies. If we can identify bladder cancer early on, before the disease has advanced, then we can save more lives.”

Dr Joost Boormans, a member of the EAU Scientific Congress Office and a urologist at the Erasmus University Medical Center Rotterdam, said: “Research of this nature is very encouraging as it shows that our ability to identify molecular alterations in liquid biopsies such as urine that might indicate cancer is constantly improving.

“While we do need to develop more accurate diagnostics, it’s unlikely that we’ll have a mass screening programme for bladder cancer in the near future. Where a urine test for genetic mutations could show its value is in reducing cystoscopies and scans in bladder cancer patients who are being monitored for recurrence, as well as those referred for blood in their urine. A simple urine test would be far easier for patients to undergo than invasive procedures or scans, as well as being less costly for health services.”

Difference between “growers” and “showers” revealed

A scientific definition to determine whether a man’s erection can be deemed a “grower” or a “shower” has been produced by researchers.

The findings are presented today at the European Association of Urology (EAU) Congress in Milan.

Urologists based at three hospitals and a clinic in Madrid conducted ultrasound scans on 225 men in both flaccid and then erect states.

The researchers, led by Dr Manuel Alonso-Isa, a urologist at the University Hospital HM Puerta del Sur in Madrid, Spain, had hoped to find factors among the men that would predict if they fell into one of these categories, which could be used to help make surgical decisions.

“It is important to be able to predict if a patient is a grower or a shower as when we see them, they are usually in a flaccid state,” he said. “If they grow a lot when they get an erection, it might mean they need a different surgical approach compared to someone who doesn’t grow much.”

When they examined the data, the extent of the men’s penis growth followed a pattern – a standard distribution curve – that allowed them to set parameters on each category.

They found that men whose penis increases in size by more than 56% when erect compared to a flaccid state could be considered “growers”. Those who saw an increase in size of less than 31% were “showers”.

Most men in the study, however, fell into a “grey zone” in between the two categories. Only 24% of the men were growers while 25% were classified as showers.

Unfortunately, the researchers, who also included urologists at the HM hospitals and the ROC Clinic in Madrid, found no correlations between age, weight, smoking status or other co-morbidities, and penis growth. Men who were showers, however, tended to have longer penises when flaccid than growers – an average of 11.3cm compared to 8.8cm.

They also found that the size of the fibrous tissue known as the tunica albuginea, which surrounds the spongy erectile tissue inside the penis, did not predict how much a man’s penis might grow. But they did find in men who were growers, the tunica albuginea became thinner than in men who were showers.

“This makes sense as the tissue is being stretched further,” said Dr Alonso-Isa. “So it could be that this tissue has more elastic fibres in men who are growers than those who are showers. But we need to do more research to prove this hypothesis.”

He said there may also be other factors they didn’t look at that play a role.

“In the meantime we have defined what constitutes a ‘grower’ or a ‘shower’ in a scientific way, which will be important for the future,” said Dr Alonso-Isa.

Commenting on behalf of the European Association of Urology, Professor Maarten Albersen, a urologist at the University of Leuven, Belgium, said while there may not be any medical consequences to being a shower or a grower, it was something that often weighed on the minds of patients.

He said: “This is a frequent area of concern for our patients and the emphasis should be on normalising baseline and erectile length for all.”

New technique reduces postoperative complications in prostate cancer surgery

Surgeons in Germany have shown a small technical change to keyhole surgery for prostate cancer can more than halve one of the most common post-operative complications – where lymphatic fluid collects in the pelvis.

The technique involves creating a small flap in the peritoneum – the lining of the abdomen – and attaching this flap down into the pelvis. This creates a route for lymphatic fluid to escape from the pelvis into the abdomen where it can be more easily absorbed.

The findings are presented at the 2023 European Association of Urology annual Congress in Milan.

Around 10 percent of patients whose prostate cancer and lymph nodes are removed through robot-assisted keyhole surgery require treatment for symptoms caused by lymphatic fluid collecting in the pelvis, known as lymphocele. Lymphocele can also be seen in nearly a third of patients when they were systematically checked, without them reporting symptoms.

Symptoms include superinfection, pain in the pelvis, pressure on the bladder, and swollen legs due to compression of the veins. If left untreated, symptomatic lymphocele can lead to serious infections or deep vein thrombosis.

Draining a lymphocele can take from three days to three weeks, with treatment complete only when the fluid is no longer accumulating. For some patients, this requires a stay in hospital.

Urology specialist Manuel Neuberger from University Medical Centre Mannheim and Heidelberg University said: “When they’ve only just returned home following a cancer operation, the last thing patients need is to return to hospital with this kind of complication, which unfortunately is fairly common. If drainage doesn’t cure the problem, then – in rare cases – the final treatment is to create an artificial opening in the peritoneum, which provides a route out for the lymph so it’s no longer stuck in the pelvis. As it’s such a simple step, why not create a flap as standard, to prevent the condition in the first place?

“Previous studies of the technique have been inconclusive, so we designed a larger, more robust trial to ensure our findings were statistically significant.”

The trial involved over 550 patients and four different surgeons working at University Medical Centre Mannheim, who were only informed whether a patient was to have a peritoneal flap once the rest of the operation had been completed. Patients were also randomised between the two groups – with flap or without – taking into account other factors that might increase the risk of lymphocele, such as diabetes, the extent to which lymph nodes were removed, whether they took anti-coagulants and the surgeon doing the operation. The patients were followed up for six months following the operation.

During the six month follow-up period, only 10 patients in the peritoneal flap group had developed a symptomatic lymphocele, compared to 25 in the control group. At the time of discharge, 20 patients in the flap group had lymphocele with no symptoms, compared to 46 in the control group. During the follow-up, this had risen to just 27 in the flap group, but 74 in the control group.

Professor Philip Nuhn, Professor of Urology at University Medical Centre Mannheim, who led the research, said: “Using the peritoneal flap reduced the incidence of lymphocele from nine percent to less than four percent. We now use this as the new standard in Mannheim, and hope that – following these results – it will become common practice elsewhere as well.”

Professor Jochen Walz, from the EAU Scientific Congress Office and the Institut Paoli-Calmettes Cancer Center in Marseille said: “Most problems in these operations are linked to the lymph node removal, rather than the prostate surgery itself. Removal of the lymph nodes allows us to see if the cancer has spread, so it’s important to do, particularly as surgery is now mainly used in higher risk patients. Creating a peritoneal flap is a simple, small, easy and quick procedure that takes about five minutes to complete. It is totally safe and this trial has shown it can substantially reduce complications, so there’s no reason why surgeons should not now do this as standard.

“Randomised control trials to evaluate technical changes in surgery are notoriously difficult to do – but this study has shown that they are both possible and effective. That’s good news for surgeons and for patients, who will benefit from better outcomes as a result.”