̽��ֱ�� of Cambridge - Stroke Association

Lab-grown ‘small blood vessels’ point to potential treatment for major cause of stroke and vascular dementia

cjb250 — Thu, 16 Nov 2023 16:00:19 +0000

̽��ֱ��study, published today in Stem Cell Reports, also identifies a drug target to ‘plug’ these leaks and prevent so-called small vessel disease in the brain.

Cerebral small vessel disease (SVD) is a leading cause of age-related cognitive decline and contributes to almost half (45%) of dementia cases worldwide. It is also responsible for one in five (20%) ischemic strokes, the most common type of stroke, where a blood clot prevents the flow of blood and oxygen to the brain.

̽��ֱ��majority of cases of SVD are associated with conditions such as hypertension and type 2 diabetes, and tend to affect people in their middle age. However, there are some rare, inherited forms of the disease that can strike people at a younger age, often in their mid-thirties. Both the inherited and ‘spontaneous’ forms of the disease share similar characteristics.

Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute, ̽��ֱ�� of Cambridge, used cells taken from skin biopsies of patients with one of these rare forms of SVD, which is caused by a mutation in a gene called COL4.

By reprogramming the skin cells, they were able to create induced pluripotent stem cells – cells that have the capacity to develop into almost any type of cell within the body. ̽��ֱ��team then used these stem cells to generate cells of the brain blood vessels and create a model of the disease that mimics the defects seen in patients’ brain vessels.

Dr Alessandra Granata from the Department of Clinical Neurosciences at Cambridge, who led the study, said: “Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease. Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us.

“That’s why we turned to stem cells to generate cells of the brain blood vessels and create a disease model ‘in a dish’ that mimics what we see in patients.”

Our blood vessels are built around a type of scaffolding known as an extracellular matrix, a net-like structure that lines and supports the small blood vessels in the brain. ̽��ֱ��COL4 gene is important for the health of this matrix.

In their disease model, the team found that the extracellular matrix is disrupted, particularly at its so-called ‘tight junctions’, which ‘zip’ cells together. This leads to the small blood vessels becoming leaky – a key characteristic seen in SVD, where blood leaks out of the vessels and into the brain.

̽��ֱ��researchers identified a class of molecules called metalloproteinases (MMPs) that play a key role in this damage. Ordinarily, MMPs are important for maintaining the extracellular matrix, but if too many of them are produced, they can damage the structure – similar to how in ̽��ֱ��Sorcerer’s Apprentice, a single broom can help mop the floor, but too many wreak havoc.

When the team treated the blood vessels with drugs that inhibit MMPs – an antibiotic and anti-cancer drug – they found that these reversed the damage and stopped the leakage.

Dr Granata added: “These particular drugs come with potentially significant side effects so wouldn’t in themselves be viable to treat small vessel disease. But they show that in theory, targeting MMPs could stop the disease. Our model could be scaled up relatively easily to test the viability of future potential drugs.”

̽��ֱ��study was funded by the Stroke Association, British Heart Foundation and Alzheimer’s Society, with support from the NIHR Cambridge Biomedical Research Centre and the European Union’s Horizon 2020 Programme.

Reference
Al-Thani, M, Goodwin-Trotman, M. A novel human 1 iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases. Stem Cell Reports; 16 Nov 2023; DOI: https://doi.org/10.1016/j.stemcr.2023.10.014

Cambridge scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that supports these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke.

Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease

Alessandra Granata

Alessandra Granata/ ̽��ֱ�� of Cambridge

Disease mural cells stained for calponin (mural cells marker, green), collagen IV (magenta) and DAPI (nuclei, blue)

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One in ten stroke survivors need more help with taking medication

cjb250 — Mon, 12 Mar 2018 02:51:21 +0000

According to the Stroke Associations, as many as four in ten people who have had a stroke, go on to have another one within ten years. As a second stroke carries a greater risk of disability and death than first time strokes, it is important that survivors take medicine daily to lower their risk. There are around 1.2 million stroke survivors in the UK, and at least a third suffer from severe impairments, potentially making adherence to their medicine difficult.

Half of survivors of stroke are dependent on others for everyday activities, though the proportion dependent on others for medicine taking or needing more practical help with tablets is not known.

To examine the practical support stroke survivors living in the community need and receive with taking their medicines, researchers at the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London carried out a postal questionnaire study. ̽��ֱ��researchers developed the questionnaire together with stroke survivors and caregivers. ̽��ֱ��questionnaire was completed by 600 participants across 18 GP practices in the UK.

More than half (56%) of respondents needed help with taking medication. This included help with prescriptions and collection of medicines (50%), getting medicines out of the packaging (28%), being reminded to take medicines (36%), swallowing medicines (20%) and checking that medicines have been taken (34%). Being dependent on others was linked to experiencing more unmet needs with daily medicine taking.

Around one in ten (11%) of respondents answered yes to the question “Do you feel you need more help?” ̽��ֱ��most commonly reported areas where respondents said they needed more assistance were being reminded to take medicines, dealing with prescriptions and collection of medicines, and getting medicines out the packaging. As a result, around one in three (35%) of respondents said they had missed taking medicine in the previous 30 days.

Stroke survivors taking a higher number of daily medicines and experiencing a greater number unmet needs with practical aspects of medicine-taking were more likely to miss medications.

Interestingly, the researchers found that younger stroke survivors were more likely to miss their medicines, possibly because they are less likely to receive help from a caregiver.

“Because of the risk of a second stroke, it’s important that stroke survivors take their medication, but our study has shown that this can present challenges,” says Dr Anna De Simoni from the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London. “In the majority of cases, they receive the help they need, but there is still a sizeable minority who don’t receive all the assistance they need.”

James Jamison at the Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge, who led the study as part of his PhD, adds: “Our study has shown us some of the barriers that people face to taking their medication regularly. We also learned that stroke survivors who are dependent on others are most likely to need more assistance than they currently receive.

“Our response rate was relatively low – just over one in three – so we need more research to find out if what we’ve heard from our respondents is widespread among stroke survivors. If so, this will have implications for the care provided.”

̽��ֱ��team point to the need to develop new interventions focused on the practicalities of taking medicines and aimed at improving stroke survivors’ adherence to treatment. “Advances in technology have the potential to help improve adherence, such as electronic devices prompting medication taking times,” says Jamison. “Efforts to improve medication taking among survivors of stroke using technology are already underway and have shown promise.”

̽��ֱ��research was supported by the Royal College of General Practitioners, National Institute for Health Research (NIHR), the Stroke Association and the British Heart Foundation.

Reference
Jamison J, Ayerbe L, Di Tanna GL, Sutton S, Mant J, De Simoni A. Evaluating practical support stroke survivors get with medicines and unmet needs in primary care: A survey. 2018 BMJ Open. DOI: 10.1136/bmjopen-2017-019874

Over a half of stroke patients require a degree of help with taking medicine and a sizeable minority say they do not receive as much assistance as they need, according a study published today in the journal BMJ Open.

Because of the risk of a second stroke, it’s important that stroke survivors take their medication, but our study has shown that this can present challenges

Anna De Simoni

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Researcher profile: James Jamison

James’ research seeks to understand why people sometimes do not take the medications prescribed by their GP – and then to use this to inform interventions aimed at improving their medication taking practices.

His day-to-day activities are very varied, he says. “They can involve anything from the development of research proposals, liaising with GP practices and pharmacies in the East of England to set up research studies, training health care professionals in research procedures, conducting interviews with patients, collecting questionnaire data or writing up research for publications in health care journals.”

However, the most rewarding and interesting part is coming face-to-face with stroke survivors and their caregivers to talk about their condition and the daily challenges they face, he adds.

“Working at Cambridge provides the opportunity to be part of a leading department conducting research in primary care and offers the potential to work with esteemed colleagues in the field,” he says. “ ̽��ֱ��opportunity to deliver high quality research outputs and undertake collaborations will hopefully help further my career as a successful health care researcher.”

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Concerns over side effects of statins stopping stroke survivors taking medication

cjb250 — Mon, 17 Jul 2017 08:19:58 +0000

Individuals who have had a stroke are at risk of a second stroke, which carries a greater risk of disability and death than first time strokes. In fact, one third of all strokes occur in individuals who have previously had a stroke. To prevent this recurrence, patients are offered secondary preventative medications; however, adherence is a problem with 30% of stroke patients failing to take their medications as prescribed.

To examine the barriers to taking these medications, researchers at the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ��, London (QMUL), analysed posts to TalkStroke, a UK-based online forum hosted by the Stroke Association, across a seven year period (2004-2011). ̽��ֱ��forum was used by stroke survivors and their carers.

̽��ֱ��team, led by Dr Anna De Simoni, a lecturer in Primary Care Research at QMUL and visiting researcher at the Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge, has previously used the forum to explore issues such as the impairment that can make it difficult for stroke survivors to maintain a job.

̽��ֱ��findings of the study, which looked at posts by 84 participants, including 49 stroke survivors and 33 caregivers, are published today in the journal BMJ Open. ̽��ֱ��Stroke Association gave the researchers permission to analyse the results, and to prevent identification of individuals, the team did not use verbatim comments.

Among the reasons cited by the forum users, side effects were a major factor in decisions to stop taking medication. Several contributors had experienced negative side effects and as a result had stopped taking the medication, sometimes in consultation with their GP and other times unilaterally. Others reported that they, or the person they were caring for, had stopped taking the medication after reading negative stories in the press about side effects.

Other users expressed concerns over the medication they were offered. There were conflicting views about the efficacy of the medications – some contributors believed they were very important, while others believed that their risk could be managed by lifestyle changes alone.

Contributors also reported mixed views of healthcare professionals – some felt confident in their doctor’s decision, while others questioned their decisions, some even questioning their motivation for prescribing particular drugs.

“These findings have highlighted the need for an open, honest dialogue between patients and/or their carers, and healthcare professionals,” says Dr De Simoni. “Doctors need to listen to these concerns, discuss the benefits and drawbacks of taking the medication, and be willing to support a patient’s informed decision to refuse medications.”

However, perceptions did not present the only barriers to adherence: there were often practical considerations. Drugs were sometimes too large and difficult to swallow, or a drug regime was too burdensome. ̽��ֱ��complexities of the drug regimens sometimes meant having to develop routines and strategies to ensure patients kept to them. One survivor described having to pay for the medications by credit card as she was unable to work and had no money or benefits coming in.

“By analysing people’s views as expressed in online forums, where they are more open and less guarded, we’ve seen some valuable insights into why some stroke survivors have difficulty adhering to their medication,” says PhD candidate and first author James Jamison from the Department of Public Health and Primary Care at Cambridge.

“Challenging negative beliefs about medication and adopting practices that make routines for taking medication simpler, particularly for those patients who have suffered disability as a result of stroke, should increase adherence and ultimately improve health outcomes.”

̽��ֱ��research was supported by the National Institute of Health Research, the Stroke Association and the British Heart Foundation.

For more information about statins, visit NHS Choices.

Reference
Jamison, J et al. Barriers and facilitators to adherence to secondary stroke prevention medications after stroke: Analysis of survivors’ and caregivers’ views from an online stroke forum. BMJ Open; 19 July 2017; DOI: 10.17863/CAM.10458

Negative media coverage of the side effects associated with taking statins, and patients’ own experiences of taking the drugs, are among the reasons cited by stroke survivors and their carers for stopping taking potentially life-saving drugs, according to research published today.

These findings have highlighted the need for an open, honest dialogue between patients and/or their carers, and healthcare professionals

Anna De Simoni

jarmoluk

Medications

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Stroke survivors face ‘invisible impairments’ to return to work

cjb250 — Wed, 06 Apr 2016 18:30:53 +0000

Each year, 110,000 people in England alone suffer a stroke, a quarter of whom are of working age. ̽��ֱ��UK’s stroke strategy highlights the importance for people who have had a stroke of returning to work: being unemployed is associated with physical and mental health problems, while working has positive effects on the health of people with chronic conditions. A recent study estimated the cost of stroke care in the UK to be £9 billion a year, of which almost a third (30%) is due to loss of income and productivity.

To explore the experiences of people who have returned to work after a stroke, researchers analysed the archives of TalkStroke, a UK-based online forum hosted by the Stroke Association, across a seven year period (2004-2011). It is believed to be the first study to utilise data from such forums to study barriers to staying in work after stroke.

̽��ֱ��researchers searched more than 20,000 posts for the phrases “return to work” and “back at work” and identified 60 people who had posted about the issue during the seven year period. Almost all of those who managed to return to work still experienced a range of residual invisible impairments, including memory and concentration problems and fatigue.

On the online forums, some commenters described the problems with looking ‘normal’, but not feeling the same way and how this led to a lack understanding among co-workers, but also to their own sense of feeling a fraud.

Having a supportive employer helped people ease themselves back into work and enabled survivors to make adjustments, including a gradual return to work, reduced hours and working from home. But when employers were unsupportive, survivors found this particularly distressing and stressful; some posters even reported being bullied by colleagues.

Some commenters gave specific advice to others, such as recommending speaking to their GP, but awareness was low of what do and where to seek advice if stroke-related problems persisted long-term.

“Although a stroke survivor may look like they have recovered, they can be still be affected by invisible impairments that make work difficult,” says Dr Anna De Simoni, a lecturer in Primary Care Research at QMUL and visiting researcher at the Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge.

“Conversations in the internet forums suggest we need to raise awareness of the support available to individuals, but also more widely amongst primary care professionals and employers of how they can best accommodate and support their staff.”

Perhaps surprisingly, the forums also highlighted that GPs themselves did not always understand the impairments and could often do more to support their patients. One man, aged 61 at the time of his stroke, reported that his GP was unwilling to extend his sick leave as he said the man could sit at a desk and move all his limbs and so was fit to work, yet the man suffered impairments such as walking and communication problems, limb spasms and fatigue.

In a sister paper, also in BMJ Open, the authors report how TalkStroke proved to be a powerful tool for providing advice and support for survivors and their carers. ̽��ֱ��study found that 95% of information and support requests by patients with stroke and their families in the online forum were answered in replies.

̽��ֱ��main reasons for taking part in online discussions were requests and offers of information and support, and sharing own experiences of stroke. Most information needs were around physical impairments, understanding the cause of stroke and the potential for recovery.

Professor Jonathan Mant from the Cambridge Primary Care Unit says: “Almost all requests of information and support on the forums receive an answer. In a time when GP surgeries are full and patients are waiting weeks for community appointments, these online forums can provide a way for stroke survivors and their carers to receive helpful advice and support.”

̽��ֱ��researchers were funded by the National Institute for Health Research and the Evelyn Trust.

Kate Pieroudis, Manager of the Back to Work Project at the Stroke Association said: “Employers can have a vital part to play in helping stroke survivors get back into the workplace and on the road to recovery. Stroke is incredibly complex and affects every person differently. In some cases, the long-term effects of the condition, such as communication problems or memory loss, may only become apparent in a work environment.

“With the right support, many stroke survivors can and do go back to work successfully. Planning with employers is essential so they understand how a stroke has affected an individual, and can put necessary support and adjustments in place. ̽��ֱ��Stroke Association provides information and practical advice on work and stroke to both employers and stroke survivors.”

̽��ֱ��Stroke Association’s ‘Complete Guide to Stroke for Employers’ can be downloaded here.

Reference
Balasooriya-Smeekens, C et al. Barriers and facilitators to staying in work after stroke: insight from an online forum. BMJ Open; 6 April 2016; DOI 10.1136/bmjopen-2015-009974

De Simoni, A. et al. Stroke survivors and their families receive information and support on an individual basis from an online forum: descriptive analysis of a population of 2,348 patients and qualitative study of a sample of participants. BMJ Open; 6 April 2016; DOI 10.1136/bmjopen-2015-010501

‘Invisible impairments’ can make it difficult for stroke survivors to maintain a job, according to a study from the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London (QMUL). ̽��ֱ��findings, published today in the journal BMJ Open, suggest that more needs to be done to make survivors, their GPs and employers aware of the difficulties that they may face.

Although a stroke survivor may look like they have recovered, they can be still be affected by invisible impairments that make work difficult

Anna De Simoni

Helloquence

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