Researchers from (MIB), led by Professor Nicholas Turner, Dr Sarah Lovelock and Professor Anthony Green, have developed an efficient biocatalytic manufacturing route to Molnupiravir. Experimental work was led by Dr Ashleigh Burke who developed a new enzyme, cytidine aminotransferase, to allow the production of a key Molnupiravir intermediate.

The unique approach of the 91直播 team is currently being further developed with industrial partners at multi-Kg scale to enable adoption by generic pharmaceutical manufacturers at large scale.

Professor Anthony Green said: “We are hopeful that our work will contribute to the challenge of developing a low-cost manufacturing route to Molnupiravir to allow the widest possible access to this promising COVID-19 therapy.”

The research undertaken by The University of Manchester team has been to allow pharmaceutical manufacturers around the world to take advantage of this development.

Sterling Pharma Solutions, a pharmaceutical contract development and manufacturing organisation (CDMO), has been engaged to support scale-up development and manufacturing activities utilising the novel enzyme developed by the 91直播 team. Sterling’s CEO, Kevin Cook, said: “We are incredibly proud to be working in partnership will all those involved to help improve global access to what looks to be a very promising, life-saving treatment.”

In order to maximise the impact of the new enzyme technology, Prozomix Ltd, a biocatalyst discovery and contract manufacturing organisation (CMO), will employ foundation funds to produce high-quality cytidine aminotransferase and distribute it globally free-of-charge. Any company can obtain a sample by emailing Molnupiravir@prozomix.com.

Prozomix's Managing Director, Professor Simon Charnock, said: "Establishing a new and widely employable biocatalytic route for an API has arguably never been as urgent, we feel most privileged to play our part in this collaboration."

Community pharmacy staff are to be offered training on suicide prevention, based on findings from a new study published today. As a result, a first of its kind training video has been developed and will also be available from today to mark World Suicide Prevention Day.

The research from the National Institute for Health Research Greater 91直播 Patient Safety Translational Research Centre's () mental health theme was published in the journal, .

The team conducted in-depth qualitative interviews with 25 community pharmacy staff and identified 6 key themes. The first two; relationship with patient and suitable pharmacy environment formed a basis for interacting about suicide. If supported by training, staff felt that they could maximise opportunities for contact. The need to create facilitated referral pathways and understand more about restricting access to means was recognised.

Dr Hayley Gorton who led the research team whilst at The University of Manchester, said: “This is the first qualitative interview study which has explored the important role of community pharmacy teams in suicide prevention. Our research discovered that, staff felt they could do more to support individuals if they were given training.

“It is heartening to see that pharmacists and their teams recognise that they can contribute to the suicide prevention agenda and welcome training to support them to do so.”

Community pharmacists are the most visited healthcare professionals in the UK, with pharmacy teams caring for over 1.6 million people in England alone every day. Yet, these teams are seldom mentioned in the suicide prevention plans, which are a current national and global priority.

Dr Gorton has worked with the Centre for Pharmacy Postgraduate Education (CPPE) to make the training a reality. They have produced a suicide awareness learning video aimed at pharmacy teams.

The innovative training video aims to prompt pharmacy staff to reflect on their current role in suicide prevention, and what it might be in the future. Three special guests, who speak about their experience in relation to suicide, also provide learning messages.

Dr Gorton, added: “We hope that the CPPE suicide awareness learning video is the first step in supporting our colleagues to have potentially life-saving conversations.”

The GM PSTRC mental health theme is also launching a campaign today to mark World Suicide Prevention Day, #seedsofhope with a photographic exhibition at 91直播 Town Hall. Pictures carefully selected by members of the mental health theme’s patient and carer involvement group to represent what hope means to them will be on display for the day from 10:30 until 17:30. Everyone who visits will receive a packet of seeds. Once planted pictures of the plants growth can be tweeted with using #seedsofgrowth to raise awareness of the research underway by the PSTRC to make a difference to the treatment of mental health.

A team from The University of Manchester have engineered a common gut bacterium to produce a new class of antibiotics by using robotics. These antibiotics, known as class II polyketides, are also naturally produced by soil bacteria and have antimicrobial properties which are vital in the modern pharmaceutical industry to combat infectious diseases and cancer.

The naturally produced Escherichia coli bacteria are difficult to work with as they grow in dense clumps that are incompatible with the automated robotic systems used for modern biotechnology research. By transferring the production machinery from the soil bacteria into E. coli, the 91直播 team is now making this class of antibiotics accessible for much more rapid exploration.

This breakthrough could be vital for the ongoing combat against antimicrobial resistance, as recently developed automated robotics systems can now be used to create new antibiotics in a fast and efficient way.

In this work, published in the journal , the group led by Professor Takano at The University of Manchester show the potential of this approach. By combining the bacterial production machinery with enzymes from plants and fungi, it was possible to produce new chemical compounds not previously seen in nature. Using this plug-and-play platform, it will now be possible to explore and engineer polyketides using robotic systems to develop new and diversified polyketides in an automated, rapid and versatile fashion.

Eriko Takano, Professor of Synthetic Biology said: “Nature is a huge treasure trove for powerful chemical compounds to treat a wide range of diseases. However, the most interesting chemicals often come from organisms that are difficult to work with in the laboratory.

“This has been a major bottleneck for our work on type II polyketides, a group of important chemicals, which are mostly produced by soil bacteria and other microorganisms that are challenging to grow. By successfully moving the production machinery for these compounds into the “laboratory workhorse” bacterium E. coli, we can finally produce and engineer type II polyketides in our rapid robotic systems.

“This not only allows us to trial new polyketides in an automated manner, but we will also be able to quickly rewrite the DNA sequences of the antibiotic biosynthesis pathways and combine them with new components from other organisms, such as medicinal plants and fungi, to produce variations on the antibiotic theme – including compounds that are not produced by the natural pathways, but may have enhanced or novel activities in the treatment of important diseases.”

It could take a person a whole year to make and test ten new potential antibiotics, but this automated robotic system can make thousands in that time. This would hugely decrease the time it takes for new antibiotics to reach patients, and provide the necessary agility to react to new pathogen strains and outbreaks.

 is one of The University of Manchester’s  - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

A machine learning approach for assessing images of the craters and dunes of Mars, which was developed at The University of Manchester, has now been adapted to help scientists measure the effects of treatments on tumours.

Because tumours are not uniform and different parts of them change at varying speeds, it is difficult for researchers to see what effects their treatments are having against a background of changes that would happen anyway.

Typically, to obtain meaningful results scientists have to look at average changes in tumours using many samples, often in animals. With conventional statistical methods, it can be difficult to assess the effects of treatment on individuals, as would be required for personalised medicine.

The machine learning technique was developed at 91直播 to help planetary scientists map features on planets such as Mars. It was designed to better understand the errors and uncertainties of observations, thereby enabling researchers to present their findings with confidence.

The 91直播 team, from worked in collaboration with , Head of Imaging within on studies of lab mice. They applied their machine learning technique, called Linear Poisson Modelling, to the samples and were able to demonstrate a four-fold increase in the precision of tumour change measurements that detected the beneficial effects of cancer therapies.

, from the University’s Division of Informatics, Imaging & Data Sciences, said: “The results of this study show that we can present findings which researchers can be much more certain of. This means you can get the same quality of data from one sample instead of 16.”

"This has important implications for research, meaning that instead of using 16 mice, in some studies only one is needed. This could help reduce the use of lab mice in medical research. It also opens up the potential for this technique to be used in patients by quickly and confidently identifying if drugs are having a specific effect on their tumours.”

Linear Poisson Modelling works by learning patterns within data and how they can change. Unlike other machine learning methods, such as the popular Deep Learning, it can also assess the effects of errors in data, providing as an additional output predictions of how precise its results are. The improved modelling of data also means that fewer samples are needed to provide highly accurate results.

Dr Paul Tar, who co-developed the method during his PhD project, added: “This technique is all about making the most of ‘small data’, which is common in medical studies where it is difficult to obtain large numbers of samples. Researchers use charitable or public money, so it is important that they use it in the most efficient way possible, something which this technique allows.”

Dr James O’Connor, a advanced clinician scientist, said: “Every person’s cancer is unique, which can make treating the disease challenging as a drug that works for one patient might not work for someone else. That’s why we’re increasingly looking at finding new ways to make treatment more personal, and this innovative work could be a step towards that goal. The next step will be further research to find out if that’s the case, and to help uncover this method’s potential.”

The paper, ‘,’ has been published in the journal BioInformatics. DOI: 10.1093/bioinformatics/bty115/4934935

Planetary science applications are described in ‘, (Advances in Space Research, 2015) DOI: 10.1016/j.asr.2015.03.043

The project was funded by , and Cancer Research UK. Funding for Dr Tar’s PhD was provided by . Support was provided by the at Cambridge and 91直播

Cancer

 is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

A team of scientists have created a new generation of tiny remote controlled nanorobots which could one day allow doctors to diagnose disease and deliver drugs from within the human body.

The team led by Professor Li Zhang from the , including Professor from The University of Manchester, have created the bots from a biodegradable material called spirulina algae.

The algae, sold today as a food substitute in health food shops, was a source of nourishment during the time of the Aztecs.

But it was rediscovered in the 1960s by Lake Texcoco in Mexico by French researchers.

A paper by the team, published in hails the bots’ biodegradability as a new concept, in which an iron magnetic coating helps fine-tune the rate which they degrade.

The nanorobots can be remotely controlled within complex biological fluids with high precision using magnetic fields.

The team also describes how the bots are able to release potent drug compounds that are able to attack cancer cells.

However more work still needs to be done on motion tracking, biocompatibility, biodegradation, and diagnostic and therapeutic effects before clinical trials can take place.

Professor Zhang said: “Rather than fabricate a functional microrobot from scratch using intricate laboratory techniques and processes, we set out to directly engineer smart materials in nature, which are endowed with favorable functionalities for medical applications owing to their intrinsic chemical composition. For instance, because these biohybrid bots have a naturally fluorescent biological interior and magnetic iron-oxide exterior, we can track and actuate a swarm of those agents inside the body quite easily using fluorescence imaging and magnetic resonance imaging.

“Our microrobots have the ability to sense changes in environments associated with the onset of illness and that makes them a promising probe for remote diagnostic sensing of diseases.

“We must now develop this technology further so we are able to fine tune this image–guided therapy and create a proof of concept for the engineering of multifunctional microrobotic and nanorobotic devices.”

Professor Kostarelos said: “Creating robotic systems which can be propelled and guided in the body has been and still is a holy-grail in the field of delivery system engineering.

“Our work takes advantage of some elements offered by nature such as fluorescence, degradability, shape.

“But we add engineered features such as magnetisation and biological activity to come up with a the proof-of-concept behind our bio-hybrid, magnetically propelled microrobots.

He added: “We are still in early days of development since any such robotic system would need to be either completely and safely degraded, or it will need to be removed or excreted from the body after it has finished its work.

“But nevertheless, our work provides the first ever example of how this could be possibly achieved by degradation.

“The potential of these bots for controlled navigation in hard-to-reach cavities of the human body makes them promising miniaturized robotic tools to diagnose and treat diseases which is minimally invasive.”

The research teram included the Chinese University of Hong Kong, The  University of Edinburgh and The University of Manchester.

The paper ‘Multifunctional biohybrid magnetite microrobots for imaging-guided therapy’ is published in Science Robotics (DOI: 10.1126/scirobotics.aaq1155) on 22 November, 2017.

A led by The University of Manchester has discovered that so called ‘lonely’ microbes, those living at low population densities, are more likely to mutate causing higher rates of antibiotic resistance.

After analysing 70 years of data and nearly 500 different measurements of mutations, the study shows individual microbes – such as bacteria – found in denser microbial populations mutate much less than microbes in sparser groups.

Mutations in bacteria can result in a range of outcomes, including becoming antibiotic resistant. Therefore, this research could pave the way to a better understanding of antibiotic resistance, contributing to more effective ways of combating the rise of antibiotic resistant ‘superbugs’.

The study, in collaboration with the Universities of Keele and Middlesex, follows the team’s that also looked at the relationship between mutation rate and population density of microbes, but only in one specific bacterium, E. coli. That study found that ‘lonely’ bacteria were nearly ten times as likely to mutate to resist antibiotics as those living in dense populations.

This research, funded by the , expands massively on those initial findings by analysing mutation rates from all branches of life, analysing 68 independent studies of 26 species of microbes, even including viruses.

This was followed with hundreds more experiments, using nearly 2 trillion microbial cells which, though tiny, if laid end to end, would stretch from 91直播 to Newfoundland in Canada (nearly 4000km). The findings show that the initial discovery is repeated for multiple antibiotics that target bacteria and even yeast.

, from the University’s and senior author of the study, said: ‘Spontaneous mutations fuel evolution, but when that mutation leads to something more serious, such as resistance to antibiotics, it becomes an issue. According to the World Health Organisation (WHO), if resistance continues rise, by 2050 it would lead to 10 million people dying every year.

‘That is why the particular mutations we looked at in the lab are those related to antibiotic resistance’.

The WHO says the issue threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi and is an increasingly serious threat to global public health.

The authors call their finding ‘density-associated mutation-rate plasticity’, or DAMP. DAMP is a way these mutation rates vary with the microbe’s environment. The researchers found that DAMP could play a key role in reducing the mutations that cause antibiotic resistance.

Dr Krašovec, from the and lead author of the study, explains: ‘In our analyses DAMP gives bacteria a lower chance of becoming antibiotic resistant at higher population densities. We anticipate that DAMP affects the course of evolution more generally and understanding its causes and effects will help understand and control evolution.

‘What’s exciting about DAMP is that it requires protein molecules that do the same thing in very different microbes, meaning that we can start to understand why mutation rates vary like this. This means that our results could be the first step towards manipulating microbial DAMP clinically as a way to slow the evolution of antibiotic resistance.’

Reference: This paper was published in Plos Biology. Rok Krašovec , Huw Richards , Danna R. Gifford, Charlie Hatcher, Katy J. Faulkner, Roman V. Belavkin, Alastair Channon, Elizabeth Aston, Andrew J. McBain, Christopher G. Knight. Published: August 24, 2017 https://doi.org/10.1371/journal.pbio.2002731 

A scheme launched by the Department of Health in 2011 to help patients stick to their drug regimens has been so successful, that in its first five years, it will save NHS England £517.6m  in the long-term, a team of health economists has found.

Lead researcher from The University of Manchester says – a free scheme where community pharmacists help patients take new medicines  - has improved medicines adherence by 10%.

The study was conducted by experts at The Universities of Manchester, Nottingham, UCL and a Patient and Public Representative.

Even in the short term, say the team, the scheme –where pharmacists are paid £24.60 each time they look after a patient as part of NMS has saved the NHS £75.4m.

The team used self-reported adherence at 10 weeks, considered the minimum time required to demonstrate behavioural change in a sample of 503 patients.

She said “On the basis of the evidence we have gathered for this research, we strongly  recommend that NMS should continue to be commissioned in the future.

“Our study suggests NMS  increased patient medicine adherence compared with normal practice, which translated into increased health gain at reduced overall cost.

“This is a simple intervention which has been popular with community pharmacists and patients, and is transferable into most therapeutic areas.

“Some medicines, for example,  can have early adverse effects but they subside over time such as anti-depressants.

“And we also believe these findings are likely to have applicability to other health care systems, including those based on insurance.”

From inception of the NMS to the end of August 2016, 3.59 million consultations have been claimed for with over 820 000 in the year 2015/16 – according to the researchers.

Of 11,495 community pharmacies in England, 91.2% had delivered the NMS to at least one patient between November 2011 and January 2014, according to NHS Business Services Authority.

She added: “These are significant  benefits for two reasons because so many patients have experienced the service. 

“We also think our figures are probably on the conservative side given probable patient recruitment bias, use of self-report of adherence, and the assumption that all the patients in the intervention arm actually received the NMS.”

Non-adherence is common in diseases such as chronic obstructive pulmonary disease where only 33% of patients continue their drugs after 10 weeks. In  schizophrenia the figure is  52%,  asthma: 67%; and diabetes 78%.

According to previous research, the costs to NHS England of non-adherence is over £930 million per year  in just five diseases: asthma, type 2 diabetes, high cholesterol/coronary heart disease, hypertension and schizophrenia. 

To tackle the problem –which causes reduced quality of life, increased hospitalisations and premature deaths -  the Department of Health launched  the service six years ago.

The open access paper, ',' was published in PharmacoEconomics. doi: 10.1007/s40273-017-0554-9

Researchers at the Universities of Manchester and York found the enzyme in Aspergillus oryzae, a kind of fungus used for making soy sauce. The discovery,  was published in .

The enzyme鈥檚 greatest impact could be in a class of medications called monoamine oxidase (MAO) inhibitors. One such example of this kind of drug is Rasagiline. Rasagiline helps Parkinson sufferers by increasing a substance in the brain that affects motor function.

These substances help reduce the involuntary tremors that are associated with the condition. The medicine works in both early and advanced Parkinson鈥檚, and is especially useful in dealing with non-motor symptoms of the condition, like fatigue.

The team, led by Professor Nick Turner, Professor of Chemical Biology from the 91直播 Institute of Biotechnology (MIB), have identified a new biocatalyst (RedAm) that accelerates a process called reductive amination.

Reductive amination is one of the most important methods for the synthesis of chiral amines, which are important chemical building blocks in the production of pharmaceutical products.

The discovery of RedAms means more efficient routes for chiral amine synthesis, including medications such as Rasagiline. The application of RedAms will result in a dramatic reduction in time required for synthesis which will also have a positive impact on the costings and manpower needed to produce chiral amines.

A recent analysis of drugs approved by America鈥檚 Food and Drug Administration (FDA) found that approximately 40 percent of new chemical entities (NCEs) contain one or more chiral amine building blocks. This means this new enzyme could also be key to improving the manufacture of numerous other medications on the market treating multiple conditions.

There is currently no cure for Parkinson's, but there are a range of treatments to control the symptoms. However, medication such as Rasagiline is the main treatment for Parkinson's. Every hour, someone in the UK is told they have Parkinson's. One person in every 500 has Parkinson's. That's about 127,000 people in the UK.

Professor Nick Turner said: 鈥楾his is a very exciting discovery from both a chemistry and pharmaceutical perspective. It is the first enzyme of its kind that has these properties and has the potential to improve the production of this and other important drugs.鈥�

University of Manchester researchers together with their UK and overseas collaborators have found out that more than one third of 1,400 people with high blood pressure have not been taking their blood pressure medication.

High blood pressure is the single most important risk factor for health loss and premature death globally, and although treatment is proven to be effective, target blood pressures are only achieved in 40-50% of patients. This is likely to be largely caused by high numbers of patients not taking their medicines correctly, or at all.

The scientists have used a mass-spectrometry technique to examine blood and urine samples from almost 1,400 people in the UK and Czech Republic.

They found that non-adherence to the blood pressure lowering drugs was high at 41.6% in the UK and 31.5% in the Czech Republic. Furthermore, with each additional prescription, the rate of non-adherence increased by 85% and 77% respectively.

from The University of Manchester, who led the study, said: “We suspected that some patients haven’t’ been taking their medications on a regular basis but this analysis shows how high that figure is.

“Clearly, the more blood pressure lowering drugs are prescribed, the higher the risk that the patients will not be taking them on a regular basis. We also showed that diuretics are particularly poorly taken.”

The results from this analysis, show that four easy-to-collect parameters: patients’ age, sex, the number of blood pressure lowering medications and the diuretics together can provide a good measure of the risk of not taking the medications on a regular basis.

The researchers believe that in the future they can develop even better formulae to estimate the risk of not taking blood pressure lowering drugs without a need of a urine/blood analysis.

This will be particularly useful in countries with limited resources, as Professor Tomaszewski explained. “Not all countries will have sufficient expertise and the financial capacity to invest in technology that we are using.”

Professor Tomaszewski’s research team has just been awarded £750,000 by the to further the understanding of non-adherence to antihypertensive treatment.

Professor Tomaszewski said: “We are thrilled by this generous award from the British Heart Foundation. Our collaborative OUTREACH study brings together the key UK centres and researchers in the field of hypertension to examine how our urine test can help patients taking their blood pressure lowering medications on a regular basis.”

The paper, ‘’ was published in the journal Hypertension.

The University of Manchester is part of a new consortium which will develop new CT and MRI scan techniques and biomarkers to look at the accumulation of compounds in the body caused by drugs and the harm they may cause – potentially improving patients’ safety and the development of new treatments.

The TRISTAN project, (Translational Imaging in Drug Safety Assessment) is a public-private partnership supported by involving organisations across Europe. The University of Manchester is a major part of this, receiving funding to develop scanning techniques for so-called imaging biomarkers for drug-induced liver and lung disease.

The researchers believe that by refining these techniques to adapt scans for specific compounds they can spot the early signs of disease, tailor individual treatments and identify problems with new drugs early in their development – potentially saving time and money.

One part of the package will be to develop a trial in rheumatology and patients who have drug induced lung toxicity. By scanning them, the researchers hope to refine techniques to spot this early on and identify which patients are most susceptible.

, a National Institute for Health Research Clinical Lecturer in Rheumatology, who is leading this part of the research in 91直播, said: "Some drugs can cause inflammation and damage in the lungs. We hope to develop scans that can identify early lung changes so that quick action can be taken to minimise harm to the patient. The scans may also help identify drugs which are at high risk of causing lung problems so they are not developed further.”

Another part of the project will investigate drug interactions and drug-induced liver disease. Specifically the researchers will look for the presence of imaging biomarker gadoxetate in liver cells. This will enable them to develop predictive models to help with the development of new drugs with less safety concerns.

, principal investigator and Reader in the School of Health Sciences/ Pharmacy, is leading this section of the project. She said: “Quite often drugs are far down the line of development before potential harmful side-effects are discovered. Use of imaging biomarkers and predictive models could help identify a drug that is not a good candidate much earlier, saving a lot of money and research time.”

Overall the five-year, European-wide project is budgeted at €24m. TRISTAN is led by Bayer and coordinated by the European Organisation for Research and Treatment of Cancer (EORTC). The University of Manchester will receive around £1.1m. Partners in this part of the work will be the University of Leeds, University of Sheffield/Sheffield Teaching Hospitals NHS Trust.

It will also involve The University of Manchester spin-out company Bioxydyn, a specialist provider of ground-breaking MRI applications and imaging services.

, a co-investigator and Director of (BRC) said: “Researchers across Greater 91直播 are working towards a more personalised approach that matches individuals to the treatment most likely to work for them. This grant from the European Commission will complement the funding for our new BRC and support research into the use of advanced imaging biomarkers to better predict targeting of treatment and reduce the risk of side effects.”

Cancer

 is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

Flare-ups in chronic obstructive pulmonary disease, the UK’s fourth leading cause of death, can be reduced by 20% by a combined triple inhaler, according to the results of a trial of more than 2,000 people conducted by The University of Manchester.

The study, published in the Lancet, contains the results of a year-long trial involving 2,691 patients. More than a thousand of these were given a new inhaler to manage their condition, which contains three different compounds, while another thousand were given the most common globally used inhaler. A further 500 were given the triple combination but in two inhalers.

COPD is term used to describe a number of progressive lung diseases such as emphysema. The main cause is smoking, although the condition can sometimes affect people who have never smoked. All participants in the trial were current or former smokers.

This group as a whole would expect to experience average 1.3 exacerbations per person in a year – which are usually caused by an infection and can result in hospitalisation or death and faster progression of the disease. However the risk of an exacerbation was reduced by 20% in the group using the triple inhaler.

Professor of Respiratory Medicine at The University of Manchester, , said: “This is the first long-term study to look at the possibilities of triple therapy as a preventative measure for COPD exacerbations.

“COPD exacerbations lead to approximately 150,000 hospital admissions and 1.2 million bed-days every year in the UK, so to reduce this figure by 20% would make a huge difference, not only for patients’ quality of life, but also for the resources of the NHS.”

As well as reduced exacerbations, the trial also found that the new inhaler helped to improve lung function more generally and resulted in fewer overall symptoms. The trial is also the first study to prospectively study a biomarker for individualising treatment better.

Using a count of blood eosinophil (a type of immune cell), it was possible to identify patients more likely to have even greater benefit from the triple inhaler containing an inhaled steroid.

Professor Vestbo, who is also a consultant at where the trials were carried out, added: “Our new funding from the will further build on this research, enabling us to work towards earlier diagnosis and a more targeted approach for respiratory patients that matches individuals to the treatment most likely to work for them.”

The paper, ‘’, was published in .

The study was funded by .

The human whipworm, which infects 500 million people and can damage physical and mental growth, is killed at egg and adult stage by a new drug class developed at the Universities of Manchester and Oxford and University College London.

Current treatments for human whipworm are based on 1960s drugs initially developed for livestock and have a low success rate in people. There are also no vaccines available.

As a result there’s a desperate need for new treatments. The team from the three UK universities, whose results have been published in the journal PLOS Neglected Tropical Diseases, studied a class of dihydrobenzoxazepinones, not previously associated with controlling whipworms.

The researchers found that the compounds kill the adult stages of the whipworm much more effectively than existing drugs.

Parasite immunologist, from The University of Manchester said: “Eradicating the whipworm requires more effective drugs, improving hygiene and vaccine development. The compounds we have discovered could address the first two of these.”

Whipworm eggs are also affected by the compounds. Whipworm eggs are passed from infected faeces into people by hand to mouth contact. This often happens in unsanitary toilets or areas where people live close together. The eggs are highly resistant to extreme temperature changes and ultraviolet radiation and can remain viable in the environment for many years.

However the new compounds are effective against the eggs and could be developed into a spray which can stop infection at source.

The researchers are now modifying their compounds to make them effective enough for a treatment in humans, and one that can be turned into a product used in the developing countries most affected.

Professor Else said: “This team brought expertise from immunology, medicinal chemistry and neurobiology and really shows how combining across disciplines and institutions can lead to important new discoveries.

“Although we rarely see whipworm infection in the UK, it is a serious and damaging problem in many parts of the world and if we can develop this treatment, the lives of many people could be improved.”

The paper, ‘’, was published in PLOS Neglected Tropical Diseases. DOI: 10.1371/journal.pntd.0005359

Funding was provided by .

is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

The University of Manchester, through its Innovation Company (), has signed a licensing and research agreement with that could save the lives of millions of women around the world suffering from early stage cervical cancer.

The deal initially sees New Zealand-based Douglas Pharmaceuticals sponsor research at the University to develop the cervical cancer treatment further. Then Douglas will manufacture the therapy and drive further development, clinical trials and commercialisation on an international basis, focusing initially on a multi-centre phase 2 clinical trial in the UK.

Douglas is a family owned company headquartered in Auckland, New Zealand which is committed to improving health outcomes through price containment and accessibility to complex generic medicines developed in-house for international markets.

A burgeoning interest in drug repurposing is evidenced in the current collaboration with The University of Manchester.

Douglas Managing Director, Jeff Douglas, said: “We are delighted in the collaboration with The University of Manchester, in this promising treatment of early stage cervical cancer. We are confident in the research team which consists of Dr’s Ian and Lynne Hampson and Dr Pierre-Martin Hirsch, who is President Elect of the British Society of Colposcopy and Cervical Pathology and we look forward to progressing the Phase 2 trial with them.”

“Douglas is committed to building strong relationships in medical research for global markets with a particular emphasis on medicine repurposing."

Chief Scientific Officer, Mark Fletcher, added: “Drug repurposing is a sweet spot for Douglas right now.

“We are building on our competencies in medicine formulation and have the means to fund such opportunities at least to the point of completion of proof-of-concept clinical trials in man.

“My team is actively engaged in the search for repurposing opportunities where we can add value to first class evidenced based medical research and 91直播 is a great example of our growth in this space.”

The deal is based on the work of husband and wife team and - both molecular virologists at the University - who discovered that a drug, commonly used to treat HIV, might prevent early stage cervical cancer.

The researchers found that the drug was active against strains of human papillomavirus (HPV), which cause virtually all cases of cervical cancer.

With the help of former PhD student, Dr Innocent Orora Maranga, they carried out a successful phase 1 clinical trial in Kenya using an oral form of the drug as a pessary.

Ian said: “The HIV drug is applied directly to the cervix to catch cervical cancer in its early stages. This should reduce the need for invasive and costly surgical procedures currently used in the wealthier nations.

“When we treated Kenyan women suffering from early stage cervical cancer, we found that it wiped out pre-cancerous cells in 65 per cent, and reduced the severity of disease in 15 per cent of the trial participants with virtually no side effects.”

Lynne added: “This new non-invasive treatment has the potential to provide a revolutionary self-help therapy for women with pre-cancerous changes in the cervix.

“For poorer countries that lack surgical facilities and where the disease is most common, it could be a massive game changer.”

, Vice President and Dean of at the University is delighted with the Douglas deal and is excited about the next steps as it ‘illustrates our commitment to the university's and the Northern Health Science Alliance role in tackling global health problems’.

Dr Rich Ferrie, Director of Operations at the University’s technology transfer division, UMIP, said: “I am delighted that we have partnered with Douglas Pharmaceuticals to drive the clinical development of this exciting cervical cancer therapy, which offers hope for millions of women globally who are at risk of cervical cancer. Douglas’s experience, infrastructure and know-how will be critical success factors in our collaboration. My colleagues Ian and Lynne Hampson are already working closely with Pierre and Douglas to design the phase 2 trial which will commence in early 2018.”

Cancer

 is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet. #ResearchBeacons

A new combination of drugs, tested by University of Manchester scientists, has significantly enhanced the survival of laboratory mice with lymphoma.

According to the team, the effect of Obinutuzumab - a first-line treatment for non-Hodgkin lymphoma and leukaemia - is significantly enhanced when combined with drugs that stimulate the immune system.

The research is published in the journal Leukemia and funded by and in collaboration with.

“As a result of these findings, treatment for leukaemia and lymphoma may be improved by using this novel combination of drugs,” said the University’s who led the research.

“We were excited when we discovered that combining obinutuzumab with TLR7 activation significantly enhanced survival of animals with lymphoma by effectively eradicating tumours.

“Clearly, more work needs to be done to assess the impact of this combination on humans – but this study is nevertheless very promising.”

According to the team, the combination treatment is also able to prevent tumours from returning.

It’s success, they add, was down to the activity of “Natural Killer cells - a component of the innate immune system - and ‘CD4 helper T-cells’ which can activate a number of immune system functions.

The team tested a drug which stimulates a powerful immune response through a protein called TLR7, which is usually activated when we suffer from viral infection.

The drug is routinely used to treat patients with non-Hodgkin lymphoma and leukaemia and has revolutionised the outcome for patients with B cell malignancies.

And in the laboratory they are also to examine if there are ways to improve treatments further.

, a Postgraduate Research Fellow on the team added: “While the combination therapy was highly effective, CD8 killer T-cells did not play a major role in the therapy.

“Given the important role that killer T-cells can play in long term protection from tumour regrowth, we are looking at ways to enhance activation of these cells after obinutuzumab therapy.”

Dr Justine Alford, Cancer Research UK’s senior science information officer, said: “This study in cells and mice may have found a new way to tap into the power of the immune system and boost a type of immunotherapy for blood cancers.

“Now the challenge will be to develop this potential treatment further and find out if it has similar results in people with cancer.”

The paper A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells is available.

 The Kay Kendall Leukaemia Fund was established in 1984 under the Will of the late James Sainsbury CBE. It awards grants for research on aspects of leukaemia and for relevant studies on related haematological malignancies. Grants are awarded for first class research on innovative proposals, particularly those close to the care of leukaemia patients or the prevention of leukaemia or related diseases. Project grants are awarded twice yearly, and Intermediate, and Junior Fellowships of 3 – 4 years are awarded annually. The Fund also considers support for capital projects that will have direct benefit to leukaemia patient care.

 is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.

A joint study conducted by researchers from the universities of Liverpool and 91直播 has found a link between birth defects and certain types of epilepsy medication.

For most women who have epilepsy, continuing their medication during pregnancy is important for their health. Over the last 25 years, research has shown that children exposed to these medications in the womb can be at a higher risk of having a malformation or birth defect.

The study, published in the Cochrane Database of Systematic Reviews, aimed to understand whether pregnant women exposed to antiepileptic drugs (AEDs) during pregnancy were at higher risk of having a child with a malformation.

The majority of women with epilepsy will be required to continue antiepileptic drug treatment during a pregnancy.

Previous studies have demonstrated a significant increase in risk of having a child with a significant birth defect in the mother was taking certain antiepileptic drugs and therefore treatment decisions should be made carefully and collaboratively and aim to find a balance between maximising maternal health whilst minimising fetal risk.

As part of this systematic review 50 published studies were analysed and it was found that exposure in the womb to the AED sodium valproate was associated with a 10% chance of the child having a significant birth defect and that this rose as the dose of the drug increased.

The types of birth defect that were increased were skeletal and limb defects, cardiac defects, craniofacial defects and neural tube defects.

Children exposed to carbamazepine, topiramate or phenytoin were at an increased risk of having a significant birth defect but the exact types of defects were not clear and children exposed to phenobarbital were found to be at an increased risk of cardiac defects.

The review also found that children exposed to lamotrigine or levetiracetam were not found to be at an increased risk of significant birth defects in comparison to control children and had lower risks when directly compared to the children exposed to carbamazepine, phenytoin or topiramate.

The University of Manchester’s , who carried out the study said: “It is important that we understand all there is to know about the possible risks which may be associated with taking certain medications during pregnancy.

“Whilst the overall risks associated with exposure in the womb to valproate have been known for some time now, this systematic review brought together and re-analysed a large number of cases looking at the specific types of malformations which are increased if the mother is taking valproate during her pregnancy.

“This systematic review was not just about valproate however, it also demonstrated that use of other certain other anti-epileptic drugs also increased the risk of having a child with a malformation (but to a lesser extent than the risk increased seen associated with valproate) and that, based on current data, lamotrigine and levetiracetam were associated with the lowest level of risk.”

The full study, entitled ‘Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child (Review)’, can be found . DOI: 10.1002/14651858.CD010236.pub2

A postgraduate student from the University of Manchester is hoping to inspire the next generation of female scientists and engineers with a campaign aimed at illustrating ‘real’ women in the industry.

The campaign which launches today will showcase weekly stories of 40 ‘relatable’ female scientists from across Europe; providing an insight into their careers and how they achieved it, along with photographs of them in and out of the work place. The aim is to break down stereotypes and perceptions that roles in science and engineering are unattainable and mainly reserved for men.

Rhys Archer, a PhD researcher in Materials Science and Widening Participation Fellow who is behind the crusade, is using the opportunity to educate people about the issues around diversity in science and create a resource not only for young people but also for women who are already working in the sciences and would like to find out more about their industry peers.

After winning the online public engagement competition, ‘I'm an Engineer Get Me Out of Here’ in 2015, Rhys is using her prize money to fund the marketing campaign that includes the production of a website, social media channels and leaflets which will be given to children in schools across 91直播.

Rhys said: “I recognised a lack of female scientists and engineers in the media that can act as role models and I didn't feel this fairly represented the amount of women doing fantastic work in science, technology, engineering and maths (STEM) in both research and industry.

“The premise of the project is based on the book called Humans of New York by Brandon Stanton which is made up of photos of everyday people in the city, along with short quotes and anecdotes about their lives.

“Following this theme, I wanted to present women in STEM as real people who can actually be very relatable. Science probably isn’t the be all and end all of their existence. They are not geniuses, they are regular people who do science and happen to be female.”

For the latest blogs and case studies from Women in Science, visit the website and follow @womenofsci on Facebook, Twitter and Instagram.

Researchers at The University of Manchester have discovered that a potential new drug reduces the number of brain cells destroyed by stroke and then helps to repair the damage.

A reduction in blood flow to the brain caused by stroke is a major cause of death and disability, and there are few effective treatments.

A team of scientists at The University of Manchester has now found that a potential new stroke drug not only works in rodents by limiting the death of existing brain cells but also by promoting the birth of new neurones (so-called neurogenesis).

This finding provides further support for the development of this anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra in short), as a new treatment for stroke. The drug is already licensed for use in humans for some conditions, including rheumatoid arthritis. Several early stage clinical trials in stroke with IL-1Ra have already been completed in 91直播, though it is not yet licensed for this condition.

In the research, published in the biomedical journal Brain, Behavior and Immunity, the researchers show that in rodents with a stroke there is not only reduced brain damage early on after the stroke, but several days later increased numbers of new neurones, when treated with the anti-inflammatory drug IL-1Ra.

Previous attempts to find a drug to prevent brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new treatment.

Importantly, the use of IL-1Ra might be better than other failed drugs in stroke as it not only limits the initial damage to brain cells, but also helps the brain repair itself long-term through the generation of new brain cells.

These new cells are thought to help restore function to areas of the brain damaged by the stroke. Earlier work by the same group showed that treatment with IL-1Ra does indeed help rodents regain motor skills that were initially lost after a stroke. Early stage clinical trials in stroke patients also suggest that IL-1Ra could be beneficial.

The current research is led by , who commented: “The results lend further strong support to the use of IL-1Ra in the treatment of stroke, however further large trials are necessary.”

The paper, ‘Reparative effects of interleukin-1 receptor antagonist in young and aged/co-morbid rodents after cerebral ischemia’, was published in the journal Brain, Behavior and Immunity. DOI: 10.1016/j.bbi.2016.11.013

Paper available under open access .

Funding for the research was provided by .

A highly successful University scheme to train “high flyers” who are likely to become future leaders in academia and industry has been renewed by the Medical Research Council (MRC).

The North West England MRC Clinical Research Training Fellowship Programme in Clinical Pharmacology and Therapeutics is an initiative funded by the MRC and run jointly by the Universities of Liverpool and 91直播.

The scheme, led by Professor Sir Munir Pirmohamed, from the University of Liverpool, and Professor Christopher Griffiths , from the University of Manchester, provides world-class training to develop the next generation of research leaders in clinical pharmacology. This has been identified as a skills shortage priority area for UK across multiple stakeholders including healthcare, academia and industry.

The original scheme, started in 2010, has successfully trained 13 fellows with a focus on personalised medicine and drug safety science.

Just over £3m of funding has been awarded for the renewed scheme, the MRC providing £1.5m, and the Universities of Liverpool and 91直播 providing £150K each to the scheme.

Partnerships with four major pharmaceutical companies (Eli Lilly, Novartis, Roche, UCB Pharma) have also been formed resulting in each of them committing £300K to the scheme. The aim again is to train 13 high-calibre clinical fellows.

The scheme will focus on three important disease areas of Oncology, Infectious Disease and Inflammation and Repair and each fellow will have the opportunity to utilise expertise in Drug Safety, Stratified Medicine and Systems Pharmacology.

New fellows will develop their research project in collaboration with at least one of the industry partners and will spend time at the industry partner facilities which will foster “without walls” research opportunities.

Professor Sir Munir Pirmohamed, said: “The renewal of the scheme by MRC, together with the support from four global pharmaceutical companies, is a validation of the success of the initial programme, highlights our strengths in clinical pharmacology and allows us to continue to address the national skills shortage in this important clinical specialty”.

Professor Chris Griffiths, said: “We are delighted that this innovative and collaborative programme with industry has been renewed. It provides unique training in academic clinical pharmacology for fellows from a broad range of medical disciplines such as rheumatology, dermatology and oncology.

"Academic-industrial interfaces, as exemplified by the programme, will be an increasingly important aspect of translational research leading to high quality patient care.”

Dr Nathan Richardson, Head of Molecular & Cellular Medicine, MRC, adds: “The MRC Centre for Drug Safety Sciences at the University of Liverpool, with its strong partnerships with the University of Manchester and major pharmaceutical companies, continues to play a leading national role in understanding drug safety and off-target affects. With excellent leadership the Centre offers an outstanding environment to help the UK build a stronger cadre of clinician scientists with pharmacology skills and industry experience. We are delighted to renew our investment through this important training scheme.”

For more information regarding the scheme please visit

As part of World Antibiotic Awareness Week (14-20 November), The University of Manchester has announced a new programme of visits to local primary schools to spread the message about using these medicines in a way that helps prevent the serious problem of bacteria becoming resistant to them.

They are also supporting to spread the message about this crisis.

Humanity and the wider environment is in the ‘pre-antibiotic era’, with the natural process of bacteria evolving to resist antibiotics – and this has been speeded up because many people get antibiotics when they don’t need them (in some countries they can just buy from their corner shop), and even in the UK, people commonly fail to take their full prescription without realising this adds to antibiotic resistance.

Another major threat comes from the massive use of antibiotics in agriculture. With a lack of new antibiotics in development, this problem is already causing longer hospital stays and increased difficulty in treating illnesses such as pneumonia and tuberculosis. Ultimately it is now known to be causing millions of deaths around the world, including in the UK.

Without effective antibiotics, organ transplantations, chemotherapy and surgery such as caesarean sections become much more dangerous. Already, 25,000 people a year die across Europe from infections resistant to antibiotics.

Lydia Bagg, a fourth year said: “Working with young children is a fantastic opportunity to get them to think about different medicines. We’ll be using games and quizzes to give simple messages about reducing the spread of germs and reducing antibiotic resistance.”

The school visits are not the only activity planned by the University. , Senior Lecturer in , has formed a partnership with two prominent student societies: the Global Health Society and the Medics in Primary Schools society.

Working with the GHS, on Thursday, 17 November, members of the public are invited to attend an open evening of presentations, where local, national and international experts on subjects relating to antibiotic resistance will be presented.

Clarissa Hemmingsen, first year medical student and President of the Global Health Society said that: “Interest in this week’s event is overwhelming –it’s a brilliant way for the public and students to learn about antibiotic resistance and differences in other countries.”

The event features leading experts from Thailand, the US, and in the UK from London, Oxford and closer to home in 91直播.

Dr Harrison said: “This work all about getting the message out to people; that around the world we’ve have turned to antibiotics too often, and even used them when science shows it’s impossible for them to help, such as with a basic cold.”

He went on to say how: “There are thousands of students coming to 91直播 every year – so it’s not only the public we’re concerned about. Using support from the student societies is brilliant and makes links across different degree courses too.”

Event: , Supported by the British Society for Antimicrobial Therapy, Antibiotic Action, and Antibiotic Guardian.

Thu 17 November 2016, 17:30 – 20:30 at Citylabs, Nelson Street, 91直播, M13 9NQ

#AntibioticResistance

Antibiotic resistance: What can I do?

• Antibiotics don’t have any effect on treating colds and flu symptoms
• If you’re worried about your health then speak to a local community pharmacist, or a member of your primary health care team
• Take antibiotics exactly as prescribed, never save them for later and never share them with others
• Spread the word: tell your friends and family about antibiotic resistance
• Play your part and show you’re an Antibiotic Guardian

A major public debate will be held in 91直播 following the recent UN declaration to combat the proliferation of antibiotic resistance. Organised by Public Health England, The University of Manchester and the British Society for Antimicrobial Chemotherapy, the debate will seek for a solution to chronic over-reliance on antibiotics by patients, GPs and other health professionals.

It will be held on 28 September 2016 in Lecture Theatre A, University Place, University of Manchester from 17:00 to 20:00; all are welcome to attend.

The event, which is open to the public, follows on the announcement by UN General Secretary Ban Ki-moon that antimicrobial resistance is a “fundamental threat” to global health and safety.

The UN Declaration is only the fourth time the General Assembly has considered a health issue, and aims to prevent over 700,000 deaths a year because of antimicrobial resistance.

Dr Roger Harrison, Senior Lecturer and Dr David Allison, Reader in Pharmacy Education, both at The University of Manchester’s School of Health Sciences and key personnel in the debate said it was absolutely essential to deal with antimicrobial resistance.

“Put simply, we have over-used the same old antibiotics for far too long, and the bacteria are increasingly getting wise. Simple infections are starting to become more and more untreatable, and urgent international action is required at all levels”.

“This includes better understanding of what leads to resistance, better surveillance and regulation of antibiotic usage and development of new antibiotics and improved diagnostic methods for infections. The need to educate health professionals and public to prevent drug resistant infections cannot be ignored – and that is one of the key messages for our debate.”

As well as the efforts by DRs Harrison and Allison, fellow scientists, researchers and pharmacy undergraduate students in The University’s Faculty of Biology, Medicine and Health have been at the forefront of reducing needless antibiotic prescribing in England.

Public Health England is keen to use the debate to increase awareness of the Antibiotic Guardians campaign – a mass movement to provide grassroots support for reduced antibiotic prescribing and use.

“91直播 has the highest number of Antibiotic Guardians than any other metropolitan area, and we are committed to building on this fantastic base to ensure unnecessary use of antibiotics is completely eliminated,” said Dr Diane Ashiru-Oredope from Public Health England.

This event will be followed by another public debate, focusing on the global impact of antibiotic resistance, again at The University of Manchester and led by the Universities Global Health Society, on Nov 17th, to help mark World Antibiotic Awareness Week and European Antibiotic Awareness Day.

Two newer epilepsy drugs may not harm the thinking skills or IQs of school-aged children whose mothers took them while pregnant – but an older drug is linked to cognitive problems in children, especially if their mothers took high doses – according to new research from The University of Manchester.

Valproate, one of the most commonly prescribed antiepileptic medications, has been associated in the past with birth defects and developmental problems. However, two newer drugs – levetiracetam and topirimate – have had little or no investigations into their developmental impact until this latest research, published in the August 31, 2016, issue of Neurology®, the medical journal of the American Academy of Neurology.

Lead researcher and author of the paper Dr Rebecca Bromley, of The University of Manchester’s School of Biological Sciences, said expectant mothers had to know the possible impacts their drug regimes may have on unborn children.

“Over the past few years, doctors have been moving away from prescribing valproate to pregnant women, shifting them to newer antiepileptic drugs. But, until now, there hasn’t been any definitive research to understand what implications for IQ and development two of these drugs may have.

“Working with funding from Epilepsy Research UK, our team was able to undertake a rigorous set of tests on the children of 171 women who had taken one of the three drugs while pregnant. From the results, we have concluded that – at the moment – levetiracetam and topiramate have no discernable impact on childhood intellectual development.

“However promising a start our findings are, we do acknowledge larger studies need to be carried out over a longer period of time to ensure these drugs do not change the thinking abilities of children in the future.”

The 171 mothers were identified using the UK Epilepsy and Pregnancy Register; each had a child between five and nine years old. Of these 171 women, 42 had taken levetiracetam, 27 had taken topirimate and 47 had taken valproate while pregnant – an additional control group of women with similarly-aged children who had not taken any antiepileptic drug while pregnant was also included in the study.

Dr Bromley and her team performed tests on their children to measure IQ, verbal and non-verbal reasoning, the speed at which they could process visual information and their memory skills.

Regardless of the level of dose of medication, the topirimate and levetiracetam-prescribed group showed no discernible difference in IQ or thinking skills compared to the control group.

However, the valproate group had an average IQ 11 points lower than the control, levetiracetam and topirimate cohort.

“Expectant mothers with epilepsy are likely to need to continue their drug regime during pregnancy and this may involve maximising the health of the mother while keeping the risks to the foetus as low as possible. Whilst some women will be able to take one of the newer drugs, others may require treatment with valproate and they should be informed of both the risks and benefits of treatment.” concluded Dr Bromley.

A team led by from The University of Manchester found that the anti-inflammatory drug completely reversed memory loss and brain inflammation in mice.

Nearly everybody will at some point in their lives take non-steroidal anti-inflammatory drugs; mefenamic acid, a common Non-Steroidal Anti Inflammatory Drug (NSAID), is routinely used for period pain.

The findings are published today in a paper authored by Dr Brough and colleagues, in the respected journal Nature Communications. Dr Brough and supervised PhD student Mike Daniels, and postdoc Dr Jack Rivers-Auty who conducted most of the experiments.

Though this is the first time a drug has been shown to target this inflammatory pathway, highlighting its importance in the disease model, Dr Brough cautions that more research is needed to identify its impact on humans, and the long-term implications of its use.

The research, funded by the Medical Research Council and the Alzheimer’s Society, paves the way for human trials which the team hope to conduct in the future.

Around 500,000 people in the UK have Alzheimer’s disease which gets worse over time, affecting many aspects of their lives, including the ability to remember, think and make decisions.

In the study transgenic mice that develop symptoms of Alzheimer's disease were used. One group of 10 mice was treated with mefenamic acid, and 10 mice were treated in the same way with a placebo.

The mice were treated at a time when they had developed memory problems and the drug was given to them by a mini-pump implanted under the skin for one month.

Memory loss was completely reversed back to the levels seen in mice without the disease.

Dr Brough said: “There is experimental evidence now to strongly suggest that inflammation in the brain makes Alzheimer’s disease worse.

“Our research shows for the first time that mefenamic acid, a simple Non-Steroidal Anti Inflammatory Drug can target an important inflammatory pathway called the NLRP3 inflammasome , which damages brain cells.”

He added: “Until now, no drug has been available to target this pathway, so we are very excited by this result.

“However, much more work needs to be done until we can say with certainty that it will tackle the disease in humans as mouse models don’t always faithfully replicate the human disease.

“Because this drug is already available and the toxicity and pharmacokinetics of the drug is known, the time for it to reach patients should, in theory, be shorter than if we were developing completely new drugs.

“We are now preparing applications to perform early phase II trials to determine a proof-of-concept that the molecules have an effect on neuroinflammation in humans.”

Dr Doug Brown, Director of Research and Development at , said: “Testing drugs already in use for other conditions is a priority for Alzheimer’s Society - it could allow us to shortcut the fifteen years or so needed to develop a new dementia drug from scratch.

“These promising lab results identify a class of existing drugs that have potential to treat Alzheimer’s disease by blocking a particular part of the immune response. However, these drugs are not without side effects and should not be taken for Alzheimer’s disease at this stage – studies in people are needed first.”

, published in the journal . DOI: 10.1038/NCOMMS12504

Please note, this study is experimental and doctors do not prescribe Mefenamic Acid as a treatment for Alzheimer’s Disease. For queries about treatment and care, please contact Alzheimer’s Society on 0330 333 0804. or email enquiries@alzheimers.org.uk

A period of intense debate about statins, covered widely in the mainstream media, was followed by a substantial rise in the proportion of people in the UK stopping taking the drug, according to a new study published in the BMJ.

Led by the London School of Hygiene & Tropical Medicine, supported by The University of Manchester and funded by , the study by Anthony Matthews and colleagues is the first to attempt to quantify how the controversy questioning the risk-benefit balance for statins, reflected by the UK media, may have affected the use of the drug in primary care.

The researchers found no evidence that widespread media coverage of the debate was linked to changes in the proportion of newly eligible patients starting statins, but there was an increase in the likelihood of existing users stopping statin therapy.

Statins reduce the risk of cardiovascular disease (CVD) and are widely recommended as part of the prevention strategy for patients with a high recorded 10-year CVD risk score (primary prevention) and patients who have experienced a recent cardiovascular event such as a heart attack or stroke (secondary prevention). Severe side effects associated with statins are extremely rare, but questions over the frequency with which the drugs cause problematic symptoms, such as muscle pain and weakness, have been raised in the academic press and reported in the national media.

Using data from UK primary care records, the researchers calculated the proportion of patients initiating and stopping statins for primary and secondary CVD prevention each month from January 2011 - March 2015. They analysed the data to investigate changes in statin use following a period of intense media coverage of the public debate around statins from October 2013 to March 2014.

The researchers found an 11% and 12% increase of existing users stopping statins given for primary and secondary prevention respectively following the period of intense coverage. The increase appeared to be temporary, with the overall proportion stopping the drug returning to expected levels six months after the coverage. Older patients and those who had been taking statins for longer were more likely to stop therapy.

The analysis also revealed a marked decrease in the proportion of patients receiving a 10-year CVD risk score from their GP after the period of media coverage, which the researchers say suggests other important impacts on conversations between GPs and patients regarding general cardiovascular health.

91直播 author Dr Liam Smeeth from the London School of Hygiene & Tropical Medicine said: “Our findings suggest that widespread coverage of health stories in the mainstream media can have an important, real world impact on the behaviour of patients and doctors. This may have significant consequences for people’s health.

“It’s undoubtedly important that debates around health issues are reflected in the media, who play a key role in communicating public health advice. We have seen many other instances where health-related media coverage has had an impact on patient behaviour, sometimes in a positive way, such as increases in attendance for cancer screening after coverage of celebrities developing cancer.

“However, in the case of statins, we are concerned that widespread reporting of the debate has given disproportionate weight to a minority view about possible side effects. This has dented public confidence in a drug which most scientists and health professionals believe to be a safe and effective option against heart disease for the vast majority of patients.”

from The University of Manchester’s added: “This study was made possible by accessing anonymised health records. It is another powerful example of how data that already exists in the health service can be re-used for the purpose of research, enhancing our understanding of the factors that influence human health.”

Scaling their findings up to the UK population, the researchers estimated that, assuming the intense media coverage was the cause of the observed changes, it could have resulted in more than 200,000 patients across the UK stopping statin therapy in the six months following the exposure period.

Previous research suggests that up to two-thirds of patients who stop statins will restart within 12 months, but the remainder may have stopped permanently, losing any protection their statins conferred against cardiovascular disease.

The researchers then modelled the number of cardiovascular events (such as heart attack and stroke), that may have resulted from the changes, by combining the number of people thought to be affected with established estimates for the effectiveness of statins. Based on a number of assumptions, they estimated there would be at least 2,000 cardiovascular events over the next 10 years, which would not have occurred if these patients had continued taking statins.^[2] The British Heart Foundation estimate that 188,000 hospital stays are attributable to heart attacks per year.

Dr Smeeth said: “Journalists are faced with the difficult task of reporting claims and counter claims when it comes to health research. While they are accountable for accurate, balanced and responsible reporting, scientists, journals and press offices are accountable for the accurate dissemination of research.

“Patients should have the most accurate information possible that reflects the balance of scientific evidence to enable them to make informed decisions about their health. People with concerns about statins, or who are thinking about making any important health decision, should always discuss this with their doctor.”

Professor Peter Weissberg, Medical Director at the British Heart Foundation, said: “There is no debate that patients who have suffered a heart attack or stroke should be taking statins to reduce their risk of another cardiovascular event. Evidence from numerous objective clinical trials also shows that statins are a safe and effective way of reducing risk of someone suffering a heart attack or stroke in the first place.

“It is absolutely vital that medical practice is guided by evidence, rather than strongly held personal opinions. This study shows that confidence in the evidence can be shaken by opinions published in the mainstream media and medical press and points to an important and complex relationship between doctors, patients and the media.

“No one should stop taking their statin without first discussing it with their GP.”

The authors acknowledge that their study cannot confirm that media coverage of the statins debate was the cause of the observed changes in the likelihood of stopping statins. If other external factors affecting prescribing rates coincided with the media coverage, this may have affected the study estimates. To try to rule this out they carried out two additional analyses, one using the same methods to look for changes in the use of drugs prescribed for glaucoma, and another looking at changes in statin prescribing exactly a year earlier when there was no notable media coverage. As expected, neither analyses showed associations, strengthening the researchers’ confidence in their methods and their main findings.

, BMJ. DOI: 10.1136/bmj.i3283

High workload, rigid rules, and conflicting pressures from their employers are all leading to community pharmacy staff deviating from standard procedures at times to ensure patients receive the tailored care they require, a new study from The University of Manchester has found.

The research which was funded by the National Institute for Health Research () and published in , analysed interviews with 24 practising staff working at a variety of levels in pharmacies. The interviewees discussed their views and experiences of complying with procedures that had been laid down either for safety or for other company purposes. Participants came from a variety of pharmacy types and from a range of locations across England and Wales.

In this study, funded by the NIHR Greater 91直播 PSTRC, some interviewees raised concerns that they were asked to follow rigid procedures that didn’t allow staff to use their professional judgement when caring for patients. In such circumstances, pharmacists felt that they should do what they judged to be best for safe patient care rather than following procedures to the letter. A further challenge for pharmacy staff was the need to balance safe patient care with the achievement of company targets for services such as medicines usage reviews. However, some respondents felt that they weren’t able to express their concerns about strict adherence to the procedures.

The study also highlighted that during peak times, staff were still expected to follow procedures but often had many tasks to complete at the same time, which made following procedures more difficult. For example, one participant said: “Easter weekend, the week before Christmas [and] the end of [a] week [are] usually very busy…[then] sticking to the rules becomes less of a priority.”

Lead researcher, said: “It’s clear that pharmacists under pressure don’t always follow procedures exactly. In the interests of individual patients this isn’t always the wrong thing to do, but the scale, complexity and inefficiency of some of these procedures is creating an atmosphere where staff think it isn’t realistic to know or follow every procedure to the letter.

“Pharmacy companies should look to involve their staff more in developing procedures and ensuring they can be used in practice.”

Ms Thomas added: “The study highlights the tension between standardising practice on the one hand and the need, at times, for greater flexibility on the other hand to deliver effective patient care.”

“These findings should help to inform policy makers and practitioners with regards to the factors most likely to influence the implementation, or not, of procedures in community pharmacy settings.”

The paper, ‘When procedures meet practice in community pharmacies: qualitative insights from pharmacists and pharmacy support staff,’ was published in the BMJ Open. It is freely available here:

An international clinical trial to test the first new cough drug in 50 years is being led by The University of Manchester’s Professor Jaclyn Smith. If approved, the promising new treatment could offer hope to the millions of people living with chronic cough for whom few, if any, effective treatments exist.

The new drug, called AF-219, is being developed by US-based biotech company, and is now being tested by the National Institute for Health Research’s () Translational Research Partnership (TRP) as part of a 12-week clinical trial. It involves 200 patients at 47 sites in the UK and US.

AF-219 works by selectively blocking the P2X3 receptors stopping the mechanism by which certain airway nerves become hyper-sensitized. The drug has already been shown to be effective in reducing cough frequency in several clinical studies, including an initial proof-of-concept study involving 24 patients, where AF-219 reduced the number of times people coughed by 75 per cent compared to placebo.

NIHR TRP study lead , from the Centre of Respiratory and Allergy at The University of Manchester and based at the University Hospitals of South 91直播 NHS Foundation Trust’s , said: “We are just beginning to understand how the nerves in the airways are involved in pathologic cough such as chronic cough. With recent developments in the technology to effectively measure coughs and this important new drug, we have started to see real progress in this area.”

The trial will use a cough monitor that was developed by Professor Smith and her team at UHSM and The University of Manchester, in collaboration with UK SME and supported by the NIHR South 91直播 Respiratory and Allergy Clinical Research Facility (RACRF). The VitaloJAK works by recording the cough sounds and allows the number of coughs in a 24-hour period to be counted and the effects of new therapies to be objectively quantified.

Professor Smith said: “Previously, studies relied on patient reported outcomes, which are not always reliable. This may lead to effective drugs being dismissed due to inaccurate reporting and, I believe, is a contributing factor to the lack of interest from big pharma companies in investigating new cough treatments. For the first time, we have a new drug for which we will be able to demonstrate reliably whether it can reduce coughing in our patients.”

Patient recruitment is now underway and is due to complete in the next two months.

Mark Samuels, Managing Director of the NIHR, said: “This could be the first new cough drug in 50 years. This large-scale trial takes us a step closer to being able to treat chronic cough. It offers real hope that this severe condition can be treated.”

George Freeman, Parliamentary Minister for Life Sciences, said: “It’s fantastic that the Government’s NIHR is testing this promising new treatment that could help the millions of patients suffering from distressing chronic coughs. Through our commitment to investing £1bn every year in the NIHR during this Parliament, we’re funding world class medical breakthroughs which can help NHS patients and avoid unnecessary NHS treatment costs.”

Your shoe fits the size of your foot, so why is your drug dose not tailored to your own personal characteristics in the same way? To answer this question, some of the world’s leading experts in health care and pharmaceutical science are coming to 91直播 this week.

The conference, organised by The University of Manchester and sponsored by global biosimulation and regulatory writing company, , aims to bring the latest research in ‘precision dosing’ together – this is the first time that experts in this field have got together at a dedicated event to debate and tackle barriers to introducing these advanced techniques into every day health care

This could be manifested in, for example, an app that will be used by doctors and a 3D printer in the local pharmacy making a tablet that exactly fits a patient’s need.

Professor Kay Marshall, Head of and a speaker at the conference, said: “Everyone is different and this means that they react to drugs in different ways. The emerging precision dosing field is all about harnessing the explosion of genomic data and various markers of bodily functions using mathematical modelling to make sure that individuals or groups get the best possible treatment.”

However, the use of this technique is currently restricted to research hospitals. Barriers such as legal issues, training and the availability of software all contribute to preventing precision dosing benefitting as many people as it could.

The Health Care Summit on Model-based Precision Dosing, which runs 19-20 May at Shrigley Hall Hotel, Cheshire, will seek to address these issues. It includes speakers such as Professor Catherine Knibbe from Leiden University, Netherlands, who will talk about the difficulties of making sure that children get the right doses, based on size and other individual factors.

The former Director of the Office of Clinical Pharmacology at the US FDA, Professor Larry Lesko, will talk about the challenges regulatory agencies face regarding implementation of more personalised dose recommendations at the stage of drug approval.

The Summit comes at the same time that has been appointed Certara Lecturer in Precision Dosing at the 91直播 Pharmacy School. Certara has endowed this lectureship, which is part of the University’s precision medicine initiative. A leader in the field, 91直播 is one of six initial regional centres of excellence for The Precision Medicine Catapult, the UK’s innovation centre for precision medicine.

Dr Darwich will co-chair the Summit, which also includes speakers from the United States, France, Germany, Switzerland and Australia. Discussions will range from the application of precision dosing for patients with conditions such as HIV infection and cancer, to heart failure and transplant recovery. In all of these cases, the dosing level of drugs can be optimised based on factors such as age, sex, weight and genetics – assuming the right environment exists to enable the use of the technique.

Professor of Systems Pharmacology, , convened the conference. He said: “We have the mathematical techniques to ensure that patients receive the correct drug dose for their individual needs, and to minimise any interactions that could occur with other medications they may need to take. However, the current framework in which this science works is restrictive.

“While these rules are in place for good reason, they are beginning to look outdated and by gathering this global panel of experts we hope to be able to make concrete recommendations for change leveraging various new technologies.”

For the first time, researchers have devised a method to selectively deliver drugs to a pregnant woman’s placenta without harming the foetus, in a development which could help prevent some premature births and treat conditions such as pre-eclampsia.

The University of Manchester scientists, writing in the journal Science Advances, have demonstrated that two peptides – chains of amino acids – originally used to target tumours selectively, will perform the same function on a placenta, delivering drugs which improve placental function and benefit the growing baby without causing it harm.

Many pregnancy complications are caused by the placenta not growing or functioning correctly. But currently there are no drugs that can be used to treat pregnancy complications, such as pre-eclampsia or foetal growth restriction, which affect more than ten percent of pregnant women.

Instead doctors have to induce early delivery of the baby. Premature babies are at increased risk of developing infections and cerebral palsy and throughout their lives have an increased risk of heart disease and diabetes.

The 91直播 research has the potential to avoid these problems by treating the baby inside the mother and avoiding induced labour. , the lead researcher explained: “Placentas behave like well-controlled tumours,” she said. “They grow quickly, produce growth hormones and evade the immune system.

“A lot of cancer research focuses on finding ways of delivering drugs to kill the tumour without affecting the rest of the body. We had the idea that if we could selectively target the placenta in the same way, we could deliver other drugs which help improve placental function and therefore treat pregnancy complications.”

As a result the researchers have demonstrated that in mice a growth hormone can be delivered to placentas, which has no effect on normal-sized foetuses, but helps undersized ones to grow, proving that there is potential for this method to be used in humans.

There were no signs that these drugs built up in the mouse’s organs, instead passing out of the body, and there were no drugs found in the mouse foetuses. The paper acknowledges that there may be harmful effects in mothers who have undiagnosed cancers, because the drugs will also target their tumours, but the authors suggest a screening programme would overcome these difficulties.

Dr Harris added: “Only one drug for use during pregnancy has been licensed in the last twenty years. By developing this platform we have opened up the possibility of any number of new drugs which can be adapted and then used safely to treat common and serious pregnancy complications.”

Professor Melanie Welham, Chief Executive, said: “This research demonstrates the value of novel approaches to drug delivery that could help us lead healthier, longer lives. The findings could help develop therapies that can help both the mother and particularly the unborn baby.”

The paper, ‘’, was published in the journal Science Advances and was funded by the .

Glucocorticoid (or steroid) therapy, prescribed to around half of patients with rheumatoid arthritis, is a known risk factor for developing diabetes. A study from The University of Manchester has found how the risk of diabetes increases in relation to the dosage, duration and timing of steroids.

In a paper published in the journal Arthritis and Rheumatology, the researchers looked at the records of more than 20,000 patients with rheumatoid arthritis in the UK and compared rates of new-onset diabetes in those who were prescribed glucocorticoids to those who didn’t receive glucocorticoids.

They found that glucocorticoids were associated with one new case of diabetes for every 150-200 people treated per year. However, within this group, risk was affected by the dose only in the most recent six months. Each increase of 5mg prednisolone per day carried a 25-30 percent increase in diabetes, although a dose of less than 5mg wasn’t associated with any measurable risk of diabetes compared to no treatment.

Dr Will Dixon, Director of at The University of Manchester and Honorary Consultant Rheumatologist at , led the study. He said: “Doctors treating people with arthritis have to make a decision how best to prescribe glucocorticoids by balancing the benefits against the risks. However, until now, no studies have considered how the risk changes with the dose and duration of treatment.

“This research provides important evidence for doctors to make this decision.”

As well as the 21,962 patients from the UK database, the research team also checked their results against a further 12,657 records held in the USA. Results also took into account patients’ BMI and smoking status, as well as their disease severity.

The research does not advocate that people stop using glucocorticoids as they have been used effectively since 1948 to treat flare-ups in joint pain and for longer periods at a low dose to help people who don’t respond to other treatments.

Mrs Stones is a patient with rheumatic diseases that have required steroid therapy for several decades. In this time, she has developed multiple steroid-related side effects including fractures and diabetes. She said: “It is important that health professionals communicate clearly, and transparently with patients, so that decisions can be made together. Understanding the risk of long-term steroids needs to be better communicated, as they can have life-long implications on quality of life.”

Dr Dixon said: “This research shows that low doses of steroids (below 5mg/ day) do not increase the risk of diabetes. However, there is an increased risk of acquiring diabetes for people who use them for long periods or at high doses which can now be quantified.”

The paper, ‘’, was published in the journal Arthritis and Rheumatology.

DOI: 10.1002/art.39537

Expert researchers in 91直播 have welcomed the decision by NASA to send fungus into space in order to try and create new drugs to help treat diseases like cancer and Alzheimer’s.

and his team at The University of Manchester say they are standing by to see if the month long experiment on the International Space Station using the fungus Aspergillus nidulans produces molecules capable of becoming potential medicines.

Richardson, who is Professor of Medical Mycology, explains: “This is exciting stuff. When fungi are put into stressful environments it can sometimes produce useful drugs, like penicillin. This fungus is known to produce drugs for osteoporosis and current research on earth suggests that it may produce molecules, which will help in studies to fight cancer, fungal diseases and Alzheimer’s.

“Fellow researchers at the University of Southern California (USC) have found that when the fungi are put in stressful conditions, silent secondary metabolite pathways are turned on. The hope is that by sending the fungus to the International Space Station, the stressful environment (high radiation and microgravity) may prompt the Aspergillus nidulans to produce more molecules of the types we know of and others that aren’t made when on earth. Genetic analysis of the fungus has shown that it has the potential to produce 40 different types of drugs,” he adds.

As well as having wide-ranging uses back on Earth, being able to produce drugs in space is vital as humans spend longer periods of time in space. NASA’s human mission to Mars for example, is expected to last between one and three years – some drugs will not last this long. The development of self-sustaining drug production will enable man to go further away from Earth and spend longer in space.

Specimens sent from Cape Canaveral Air Force Station in Florida on Friday (April 8) and are due to return in early May.

A new study has revealed a belief among pharmaceutical industry personnel that greater involvement of patients and the public could improve medicines research and development (R&D). The study, which is one of the first of its kind and part of the wider European Patients’ Academy (EUPATI) project, was published today in the BMJ Open.¹

Patients have become increasingly involved in managing their own health over recent years. Although still an emerging area, patient involvement in medicines R&D – in which patients are actively involved in research projects and in research organisations – is most visible in public research environments (e.g. the UK’s National Institute for Health Research) and areas where existing treatment options are limited (e.g. rare diseases).

Researchers interviewed 21 pharmaceutical industry professionals, representing 11 companies, from the UK, Spain and Poland, with diverse professional roles including pan-European roles, about their attitudes regarding Public and Patient Involvement (PPI) in medicines R&D.

Most of the professionals had positive beliefs about PPI, and many were optimistic that greater involvement of patients and the public would contribute positively to the medicines R&D process. However, those in Spain and Poland expressed more uncertainty about the benefits and value of PPI than those in the UK or with pan-European roles.

The interviewees also highlighted potential barriers to further PPI activity within the sector, including a sense that the concept was too intangible at the moment to persuade industry leaders of its importance and benefits; that organisational codes of practice currently represent obstacles to PPI; and that it may be difficult to engage public and patients if they have negative views of the sector.

As a result of the study, the EUPATI project is discussing the and has identified examples of patient/industry partnerships in this area.

Suzanne Parsons, Health Researcher at the Public Programmes Team at Central 91直播 University Hospitals NHS Foundation Trust (CMFT) and The University of Manchester, said: “We recommend the provision and wide communication of strong case studies to improve awareness of PPI and its benefits among industry professionals. To do this, we need to identify what constitutes good practice, as it is still a relatively new field.

“It would also be useful for industry to revisit codes of practice to ensure they do not serve as barriers against greater PPI activity.”

Key outputs of the project are the EUPATI Patient Expert Training Course and the EUPATI Toolbox for Medicines R&D to be launched later this month. These are for patients who are interested in learning more about the medicines R&D process and can help both patients and industry professionals implement patient involvement in medicines R&D, in order to address some of the aforementioned barriers to PPI identified in this study (i.e. patient education and industry regulatory worries).

“For different reasons, including cultural conservatism and concerns about regulatory barriers, industries have been somewhat reticent to engage directly with patients in clinical development. This approach is changing as we seek to understand and integrate patients’ views, and EUPATI is supporting patients with tools and knowledge for their meaningful involvement. Patients should be a partner in drug development, not just the subjects of studies,” explained Jane Griffiths, EMEA Company Group Chairman, Janssen Europe, Middle East & Africa.

The study was performed as part of EUPATI, a patient-led project, which involves a unique European team of academia, patient advocacy organisations and the pharmaceutical industry.

Suzanne Parsons, Bella Starling, Christine Mullan-Jensen, Su-Gwan Tham, Kay Warner, Kim Wever. What do pharmaceutical industry professionals in Europe believe about involving patients and the public in research and development of medicines? A qualitative interview study. BMJ Open 2016. ()

, Professor of Child and Adolescent Psychiatry, University of Manchester comments on a new Cochrane review of evidence for the use of medicines for attention deficit hyperactivity disorder (ADHD):

鈥淚t would be easy to draw the wrong overall conclusions from this Cochrane review.

Despite the fact that generally speaking the studies find a positive effect of methylphenidate, the Cochrane reviewers define the trials as having a 鈥榟igh risk鈥� of bias - and this leads them to say that the evidence is weak.

The basic issue that this review identifies is the poor design of studies to date in this field - specifically that the outcome measures, mainly parent and teacher report behaviour, may not have been made completely blind to whether the child was having the active medication or placebo. This leads to the Cochrane review of 'high risk' of bias.

听

听

This problem is intrinsic to many psychological treatment studies since it is difficult to find 鈥榦bjective鈥� measures of the disorder in question outside parent and teacher report.听 However until recently clinical scientists and trialists themselves in this field have been insufficiently focused on getting this aspect of trial design right (this has partly been a matter of culture within clinical trials in this field, partly that there are real challenges in finding appropriate objective measures).

It would therefore be wrong to draw the conclusion from this review that methylphenidate is ineffective.听 In fact clinical level evidence strongly supports the effectiveness of methylphenidate for many children with ADHD, and this is supported in the trial evidence (albeit with their design weaknesses as above).

The evidence for the positive effect of methylphenidate on ADHD symptoms is for instance much stronger than for psychological treatment.

My own view is that clinical scientists in this area should put more effort into finding valid objective measures of ADHD symptoms for use in trials, rather than concentrating on the use of so-called 'nocebos', as suggested in the report 鈥� a use that I think will be fraught with difficulty; partly because the incidence of unwanted-effects from methylphenidate is so variable and unpredictable.鈥�

Read the full review, 鈥楳ethylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)鈥� .

Around one in 100 patients in a study of over 500 UK general practices are at risk of receiving an inappropriate prescription and around one in 250 have no record of monitoring within the recommended time period, finds a study in The BMJ this week.

Older patients and those receiving multiple repeat prescriptions were at highest risk, the findings show.

The results “emphasise the need to give due consideration to the risks of prescribing multiple drugs and the importance of regular drug reviews, especially for patients with multiple conditions,” say the researchers.

Prescribing errors in primary care can cause considerable harm, with adverse drug events accounting for around 7% of hospital admissions in the UK, and half of these are judged to be preventable.

Prescribing safety indicators have been developed to identify patients at increased risk of hazardous prescribing, but they have not yet been assessed in general practices from across the UK.

So a team of researchers, led by at The University of Manchester, used anonymised patient data from the Clinical Practice Research Datalink (CPRD) to investigate the prevalence and predictors of prescribing safety indicators in UK general practice.

Potential of risk

Their findings are based on about one million adult patients registered with 526 general practices across the UK who were potentially at risk of a prescribing or monitoring error.

Around 5% of patients at risk triggered at least one prescribing indicator and almost 12% triggered at least one monitoring indicator.

Older patients and those prescribed multiple repeat drugs had significantly higher risks of triggering a prescribing indicator, whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator.

There was also high variation between practices for some indicators.

The researchers stress that, although prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified.

Nevertheless, they say the high prevalence for certain indicators “emphasises existing prescribing risks and the need for appropriate consideration within primary care, particularly for older patients and those taking multiple drugs.”

The high variation between practices for some indicators also suggests potential for improvement through targeted practice level intervention, they add.

The paper, ‘’ (PDF) appeared in the BMJ. DOI: 10.1136/bmj.h5501

The study was funded by .

Researchers have developed cancer drug-packed ‘grenades’ armed with heat sensitive triggers, allowing for treatment to be targeted directly at tumours, according to two studies due to be presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

The team based at The University of Manchester has been developing liposomes – small, bubble-like structures built out of cell membrane that are used as packages to deliver molecules into cells – to carry drugs into cancer cells. The challenge, as with any treatment, is to direct the liposomes and their payload directly to tumours while sparing healthy tissue.

Two new studies show the team has taken a step closer to solving this problem by fitting liposomes with a heat-activated trigger. By slightly heating tumours in the lab and in mouse models*, the researchers have been able to control when the pin is pulled so that the cancer-killing ‘grenades’ release the drug and target the cancer.

, study author and professor of nanomedicine at The University of Manchester, said: “Temperature-sensitive liposomes have the potential to travel safely around the body while carrying your cancer drug of choice.

“Once they reach a ‘hotspot’ of warmed-up cancer cells, the pin is effectively pulled and the drugs are released. This allows us to more effectively transport drugs to tumours, and should reduce collateral damage to healthy cells.

“The thermal trigger is set to 42 degrees celsius, which is just a few degrees warmer than normal body temperature. Although this work has only been done in the lab so far, there are a number of ways we could potentially heat cancer cells in patients – depending on the tumour type – some of which are already in clinical use.”

Professor Charles Swanton, chair of , said: “Liposomes are small bubbles of cell membrane that act like a cellular postal service, delivering molecules to our cells. Using them to deliver cancer medicines has been a holy grail of nanomedicine. But finding ways to accurately direct the liposomes towards tumours has been a major challenge in targeted drug delivery.

“These studies demonstrate for the first time how they can be built to include a temperature control, which could open up a range of new treatment avenues. This is still early work but these liposomes could be an effective way of targeting treatment towards cancer cells while leaving healthy cells unharmed.”

Abstracts for the research are available and .

Cancer is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.

Scientists at The University of Manchester have shown for the first time that the numbers of opiate receptors in the brain increases to combat severe pain in arthritis sufferers. 

Chronic pain – pain which lasts for more than six months – is a real problem for many people with approximately 46% of the UK population estimated to suffer from it (comprising 20% of consultations in general practice).   However, some people seem to cope better than others with pain, and knowing more about how these coping mechanisms work might help to develop new ways of treating this distressing symptom.

It has been known for a long time that we have receptors in our brains that respond to natural painkilling opiates such as endorphins, but the researchers in 91直播 have now shown that these receptors increase in number to help cope with long-term, severe pain.

By applying heat to the skin using a laser stimulator, Dr Christopher Brown and his colleagues showed that the more opiate receptors there are in the brain, the higher the ability to withstand the pain.

The study used Positron Emission Tomography (PET) imaging on 17 patients with arthritis and nine healthy controls to show the spread of the opioid receptors.

This suggests that the increase in opiate receptors in the brain is an adaptive response to chronic pain, allowing people to deal with it more easily.

Dr Brown said: “As far as we are aware, this is the first time that these changes have been associated with increased resilience to pain and shown to be adaptive. 

“Although the mechanisms of these adaptive changes are unknown, if we can understand how we can enhance them, we may find ways of naturally increasing resilience to pain without the side effects associated with many pain killing drugs.”

is the director of the 91直播 Pain Consortium which is focused on improving the understanding and treatment of chronic pain. He said: “This is very exciting because it changes the way we think about chronic pain. 

“There is generally a rather negative and fatalistic view of chronic pain.  This study shows that although the group as a whole are more physiologically vulnerable, the whole pain system is very flexible and that individuals can adaptively upregulate their resilience to pain.

“It may be that some simple interventions can further enhance this natural process, and designing smart molecules or simple non-drug interventions to do a similar thing is potentially attractive.”

Val Derbyshire, a patient with arthritis said: “As a patient who suffers chronic pain from osteoarthritis, I am extremely interested in this research.  I feel I have developed coping mechanisms to deal with my pain over the years, yet still have to take opioid medication to relieve my symptoms. 

“The fact that this medication has to be increased from time to time concerns me greatly, due to the addictive nature of these drugs. The notion of enhancing the natural opiates in the brain, such as endorphins, as a response to pain, seems to me to be infinitely preferable to long term medication with opiate drugs. 

“Anything that can reduce reliance on strong medication must be worth pursuing.”

Professor of Cognitive Neuroscience at the University, said: “Receptor imaging is challenging and requires the co-ordination of a large team to collect and analyse the images.   We are very lucky to have this technique in 91直播. There are very few places in the world where this study could have been done.”

The paper, ‘’, featured in , published by Wolters Kluwer. doi: 10.1097/j.pain.0000000000000299

The research was funded by .

Researchers in 91直播 have demonstrated for the first time the relative safety and effectiveness of treatment, eltrombopag, in children with persistent or chronic immune thrombocytopenia (ITP), as part of an international duo of studies. 

The results of the studies conducted in 91直播 by the ITP Centre, in partnership with the (CRF), both based at Royal 91直播 Children’s Hospital were published in and .

ITP is an autoimmune disorder where the immune system attacks platelets and blood fails to clot as it should.  Four in every 100,000 children develop the disorder each year globally.  The symptoms of ITP include bleeding and bruising more easily.  Frequent nose bleeds and bleeding from the gums can be common, and bruising often appears as purple patches or tiny red spots on the skin. On rare occasions bleeding can be life threatening.

The condition may resolve by itself, but for one in every four of the affected children, the condition becomes chronic persisting after primary intervention and lasting for more than twelve months.  For eight-year-old George, a patient from Royton near Rochdale who was involved in the study, having chronic ITP meant frequent visits to A&E for nose bleeds that wouldn’t stop and he would also miss out on social activities.

George’s mum, Joanne, explains: “George was diagnosed when he was four years old. I’d find myself chasing after George trying unsuccessfully to wrap a very active little boy in cotton wool.  On this new treatment, George can make the most of his childhood and he recently celebrated his eighth birthday with friends in style at a trampoline park.”

Historically, second-line treatment options for children with ITP have been scarce and, one of the earliest options, surgical removal of the spleen (splenectomy) was associated with a high risk of sepsis and thrombosis.  A better understanding about the underlying cause of ITP led to the development of the use of newer immunosuppressant agents, including rituximab.  More recently, thrombopoietin receptor agonists (e.g. eltrombopag) have been approved for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an inadequate response or are intolerant to other treatments.

Chief investigator, , Consultant Paediatric Haematologist and Honorary Lecturer at The University of Manchester, explains: “The studies, funded by , provide clinicians with much needed evidence to help decide when eltrombopag would benefit paediatric patients and provide dosage regimens suitable for paediatric patients. 

“The studies demonstrate that eltrombopag is well tolerated and effective, consistently stabilising the platelet count to over 50 X 10⁹ per litre within 2–6 weeks for 40 per cent of children receiving the treatment, compared with 0 per cent on the placebo arm.”  

Life Sciences Minister George Freeman MP said: “This important research has the potential to bring real benefits to children suffering from rare and life threatening bleeding disorders. By investing more than £1 billion a year through the National Institute for Health Research we are giving our world leading life sciences sector the ability to trial the latest 21st century medical breakthroughs.”

Professor Nick Webb, Director of the NIHR / Wellcome Trust 91直播 CRF adds: “The first ever patient to be recruited to a clinical trial at our clinical research facility in 91直播 was also the first patient globally to be recruited into the ITP study.  This research will enable patients to be more actively involved in school and social activities, and is also an historical milestone for the clinical research facility – affirming the value of having a dedicated children’s research facility to test and tailor treatments to children’s needs.” 

On the back of these studies eltrombopag was licenced by the FDA for use in children >1 year old.  EU licencing for this application is currently in progress.

University of Manchester researchers funded by Breast Cancer Now have discovered a new explanation as to why women with oestrogen receptor positive (ER+) breast cancer develop resistance to hormone treatment, and a potential new approach to overcome the problem.

Around 80% of breast cancers are ER+ and are treated with anti-oestrogen therapies such as tamoxifen and aromatase inhibitors. But around one in five of these cases recur within 10 years, and nearly all advanced cases develop resistance, which is why it’s so important that we continue to learn more about how the disease finds ways to survive in some patients and not others.

The study team, based at The University of Manchester’s , found that while short-term treatment with anti-oestrogen drugs decreased tumour growth, it increased the activity of breast cancer stem cells. They found that these stem cells were driven by a signal called NOTCH4. Their results from patient-derived breast cancers in mice and cells grown in the laboratory indicated that it was the presence of NOTCH4 that enabled the cancer stem cells to avoid anti-oestrogen treatment. In patient tumours, having high levels of NOTCH4 before treatment was linked to breast cancer spread and worse survival outcomes.

This suggested that resistance to anti-oestrogen treatment could be overcome by targeting the cancer stem cells with a NOTCH inhibitor, using the cells’ reliance on NOTCH4 as their Achilles heel.

91直播 team leader , from the Breast Cancer Now Research Unit at The University of Manchester’s Institute of Cancer Sciences said: “When treating with both tamoxifen and a NOTCH inhibitor, tamoxifen decreased the tumour growth while the NOTCH inhibitor decreased the numbers of breast cancer stem cells that could form new tumours, compared to treating with tamoxifen alone.

“This showed us that combining standard hormonal therapies with a NOTCH pathway inhibitor, or other drugs targeting breast cancer stem cells, could improve treatment of ER+ breast cancer patients by preventing relapse due to therapy resistance.”

Importantly, testing for high levels of NOTCH4, or another molecule called ALDH1, could predict whose breast cancer is likely to be resistant to anti-oestrogen drugs and which patients could benefit most from combined treatment with anti-oestrogen therapies and a NOTCH inhibitor.

Katie Goates, Senior Research Communications Officer at Breast Cancer Now, said: “This is an exciting new explanation as to why women become resistant to tamoxifen and how we could predict and prevent this by testing for, and blocking, NOTCH4 in breast cancer stem cells.

“Validating these findings will take time but general inhibitors of the NOTCH pathway are already being tested in breast cancer clinical trials. The development of resistance to cancer therapies is a huge challenge in the clinic which is why it’s vitally important that we continue to find ways to counteract it, taking us closer towards our ambitious goal of stopping women dying from this devastating disease by 2050.”

The research was published in and was funded by , the UK’s largest breast cancer charity, created by the merger of Breast Cancer Campaign and Breakthrough Breast Cancer.

Cancer is one of The University of Manchester’s - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.