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Salford, United Kingdom

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News Article | April 20, 2017
Site: www.eurekalert.org

Having a stroke damages immune cells as well as affecting the brain, research has found. The findings help explain why patients have a greater risk of catching life-threatening infections, such as pneumonia, after having a stroke. Therapies that boost survival of the affected immune cells or compensate for their damage could help improve the recovery of stroke patients, the researchers say. The study found that patients have reduced levels of protective antibodies in their blood after having a stroke, which might explain why they are more susceptible to infections. Tests with mice revealed those which experienced a stroke had fewer numbers of specialised immune cells called marginal zone B cells, which produce antibodies. Affected mice were more susceptible to bacterial lung infections, the researchers found. Loss of the B cells was caused by a chemical called noradrenaline produced by nerves activated during stroke. Researchers, led by the University of Edinburgh's Roslin Institute, found they could protect the mice from infections using a therapy to block the effects of noradrenaline. Noradrenaline is part of the body's fight or flight response. It helps to prepare the body for action and has a range of effects, such as raising heart rate, boosting blood supply and triggering the release of energy from stores. Blocking noradrenaline would probably be too dangerous in stroke patients, the researchers caution. They say development of other therapies that block or bypass the damage to the immune system could offer new approaches to help cut the risk of infection after stroke. The study could also lead to new tests to identify which stroke patients have the highest chances of developing an infection, so that they can be monitored more closely. Around one-third of stroke patients are stricken by infections, which can lessen their chances of making a good recovery. Treatment with antibiotics does not protect patients from developing infections and new therapies are urgently needed. The research is published in the journal Nature Communications and was funded by the Biotechnology and Biological Sciences Research Council and the Medical Research Council. The Roslin Institute receives strategic funding from the BBSRC. Experts from The University of Manchester and Salford Royal NHS Foundation Trust also contributed to the research. Dr Barry McColl, of The Roslin Institute at the University of Edinburgh, said: "Our work shows that stroke has damaging effects on the normal ability of the immune system to protect us from infections such as pneumonia, which are particularly life-threatening in stroke patients. This could partly explain why people who have strokes are so prone to getting infections. "We now plan to build on our findings by developing and testing new treatments that can block or bypass these immune deficits with B cells a particular target" Professor Craig Smith, on behalf of the stroke research group at Salford Royal NHS Foundation Trust, said: "Infections are a major complication of stroke and lead to a worse outcome for patients. This is an important study which provides new insights about how stroke affects the immune system, which we hope will lead to new approaches to preventing infections after stroke."


Opportunity for Patients, Families, and Caregivers to Hear Additional Details on Recently Initiated Phase I and Phase I/II Clinical Trials ALACHUA, FL--(Marketwired - May 16, 2017) - CTD Holdings, Inc. ( : CTDH), a clinical stage biotechnology company that develops cyclodextrin-based products for the treatment of disease, today announced that it will host a webinar to provide details of the Company's recently initiated Phase I clinical trial in the U.S. and Phase I/II clinical trial in the EU, both evaluating CTD's proprietary formulation of hydroxypropyl beta cyclodextrin, Trappsol® Cyclo™, for the treatment of Niemann-Pick Disease Type C (NPC). NPC is a rare and fatal genetic disease that damages the brain, lung, liver, spleen, and other organs. Speakers will include two of the site leaders from the ongoing Trappsol® Cyclo™ clinical trials, Dr. Caroline Hastings, UCSF Benioff Children's Hospital Oakland, and Principal Investigator for the U.S. trial, and Dr. Reena Sharma, Salford Royal NHS Foundation Trust, The Mark Holland Metabolic Unit, Salford, United Kingdom, and Coordinating Investigator for the EU trial. Professor Alan Boyd, a globally recognized pharmaceutical physician, will provide highlights of CTD's global compassionate use programs, some of which have been in existence since 2009. CTD will be represented on the webinar by N. Scott Fine, Chairman and CEO, and Dr. Sharon Hrynkow, Senior Vice President for Medical Affairs. Participants will be able to submit questions to the presenters. The webinar will be held: To register please go to this site: https://goo.gl/ok8e42 For further information on the clinical trials, see ClinicalTrials.Gov (NCT 02939547 and NCT 02912793) as well as CTD's website at www.ctd-holdings.com, including Frequently Asked Questions at http://www.ctd-holdings.com/cyclodextrins/faq CTD Holdings, Inc. is a clinical-stage biotechnology company that develops cyclodextrin-based products for the treatment of disease. The company's Trappsol® Cyclo™, an orphan drug designated product in the United States and Europe, is used to treat Niemann-Pick Disease Type C, a rare and fatal genetic disease. Additional indications for the active ingredient in Trappsol® Cyclo™, are in development. For additional information, visit the company's website: www.ctd-holdings.com This press release contains "forward-looking statements" about the company's current expectations about future results, performance, prospects and opportunities. Statements that are not historical facts, such as "anticipates," "believes" and "expects" or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual results in future periods to differ materially from what is expressed in, or implied by, these statements. The factors which may influence the company's future performance include the company's ability to obtain additional capital to expand operations as planned, success in achieving regulatory approval for clinical protocols, enrollment of adequate numbers of patients in clinical trials, unforeseen difficulties in showing efficacy of the company's biopharmaceutical products, success in attracting additional customers and profitable contracts, and regulatory risks associated with producing pharmaceutical grade and food products. These and other risk factors are described from time to time in the company's filings with the Securities and Exchange Commission, including, but not limited to, the company's reports on Forms 10-K and 10-Q. Unless required by law, the company assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.


LONDON--(BUSINESS WIRE)--GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva Inc (NASDAQ: INVA) today announced positive results from the innovative Salford Lung Study (SLS) in asthma, carried out amongst 4,233 patients treated by their own General Practitioner in everyday clinical practice. This open-label, randomised study showed that significantly more asthma patients initiated on treatment with Relvar Ellipta 100/25mcg or 200/25mcg (fluticasone furoate ‘FF’/vilanterol ‘VI’ or ‘FF/VI’) achieved an improvement in their asthma control compared with patients who continued to take their usual care medicines. Usual care treatment included inhaled corticosteroids (ICS) administered as monotherapy or as ICS/LABA (Long Acting Beta Agonist) combinations. For the primary effectiveness analysis, at 24 weeks a significantly higher percentage of patients with uncontrolled asthma and initiated on treatment with FF/VI achieved better control of their asthma (71%) measured by the Asthma Control Test (ACT), compared with patients continuing usual care treatment (56%), (Odds ratio 2.00, 95% CI 1.70, 2.34; p<0.001). Improvement was defined as an ACT total score ≥20 or an increase from baseline of ≥3. Statistically significant findings were also seen at 12, 40 and 52 weeks. Lead Investigator, Ashley Woodcock, Professor of Respiratory Medicine and Clinical Director for Respiratory Medicine, University Hospital of South Manchester and University of Manchester said: “I am really excited to see the results from SLS asthma. Asthma control continues to be a real challenge for patients and the healthcare community. Poor control can have a major impact on the lives of asthma patients. The effectiveness of different treatments on asthma control is difficult to investigate in a traditional double-blind randomised control trial, where the study design and intrusive monitoring can influence the behaviour of patients. In SLS, patient relevant outcomes are the major endpoints. GSK should be congratulated for running this unique study, designed to understand how asthma medicines work in everyday clinical practice.” In the study for the intent-to-treat (ITT) population, the incidence of serious adverse events (SAE) was the same in both arms (FF/VI 13% and usual care 13%). Pneumonia was a safety endpoint of special interest and a regulatory post-authorisation requirement of the European Medicines Agency (EMA). A novel aspect of the study design was that it allowed patient’s treatment to be modified throughout the study. Therefore two assessments relating to pneumonia have been performed, one based on the arm to which patients were randomised, the second based upon the treatment to which patients were exposed at the time of the event. Serious adverse events of pneumonia by randomised group were reported by 39 patients (FF/VI arm 23, 1%; usual care arm 16, <1%). These patients had 42 events and based on a pre-planned analysis non-inferiority of FF/VI to usual care was not confirmed. When these events were summarised according to the actual treatment patients were taking at the time of the event, 21 events were recorded for FF/VI and 21 events for usual care. Eric Dube, Senior Vice President and Head, Global Respiratory Franchise GSK, said: “Despite medical advances, more than half of patients with asthma continue to experience poor control and significant symptoms. The primary endpoint of this study showed that patients initiated with Relvar Ellipta treatment had twice the odds of achieving an improvement in asthma control compared with patients continuing usual care in this study in everyday clinical practice. This study has been a tremendous partnership effort between healthcare professionals, patients, academics and GSK and we would like to thank everyone who has helped to make this unique study possible.” Michael W. Aguiar, President and Chief Executive Officer of Innoviva said: “We are delighted to see the positive results from a second SLS study with Relvar Ellipta, the first being in chronic obstructive pulmonary disease. Asthma control remains a significant unmet medical need in the daily lives for many patients. We believe that this positive real world data successfully builds upon the previous clinical data to provide strong evidence of the benefits of Relvar Ellipta for the treatment of asthma.” These data will be presented in future publications and will be made available on clinicaltrials.gov. The Salford Lung Study is a Phase III multi-centre, open label randomised controlled trial (RCT). The objective of this study was to compare the effectiveness and safety profile of initiating treatment with FF/VI with usual asthma maintenance therapy over a 52 week period. All suitable patients with asthma at 74 primary care sites in and around Salford and South Manchester, UK, were identified from practice databases and invited to participate in the study by their own GP. The primary endpoint of the study was measured at week 24 in the primary effectiveness analysis population. In total, 4,233 patients with asthma who were taking an inhaled corticosteroid (ICS) with or without a long acting beta -agonist (LABA) were randomised to receive either FF/VI or to continue on their existing asthma maintenance therapy (usual care). Usual care was prescribed by the patients GP and included ICS either alone or in a combination with a LABA. In the usual care arm 36% of patients were on an ICS alone and 64% were on an ICS/LABA combination at the time of commencing study medication. The Salford Lung Study had minimal exclusion criteria and involved a broad demographic of patients. At baseline patients had a mean age of 49.8 (min 18 years) and were split by gender (males vs. female 41/59%). To enrol in the study, patients were required to have a GP diagnosis of asthma as their primary respiratory disease and be receiving maintenance therapy with an ICS with or without LABA for at least 4 weeks prior to visit 2. At baseline 72% of patients had uncontrolled asthma with an ACT total score of 5 to 19. Patients were followed for a period of 52 weeks in a normal clinical practice setting using their electronic medical record (EMR), linking primary care, secondary care and pharmacy data to collect study data. Throughout the duration of the study physicians were allowed to modify or switch treatment at any point as this would happen in normal clinical practice, the only exception being a switch from usual care to FF/VI. At weeks 12, 24, and 40 patients were telephoned to enquire about whether they had experienced any serious adverse events or non-serious adverse drug reactions. On these telephone calls patients were asked to provide responses to the ACT. At month 12 a face to face visit was carried out. The Standardised Asthma Quality of Life Questionnaire (AQLQ[S]) was also conducted at week 24 and week 52 by telephone. The study team was able to monitor all hospital admissions, outpatient and emergency department visits, as well as data from primary care (including all healthcare contacts, out-of-hours activity and prescriptions of antibiotics or oral steroids) via the electronic health records. The Intent-to-Treat (ITT) population is defined as all patients who have been randomised and received at least one prescription of study medication (e.g., FF/VI or usual asthma maintenance therapy). The primary effectiveness analysis (PEA) population is defined as all ITT patients who have an ACT total score of < 20 at baseline (Randomisation Visit). The odds ratio expressed in the results is calculated as the ratio of the odds of achieving better asthma control as a patient initiated with Relvar Ellipta and the odds of achieving better asthma control as a patient continuing on usual care. This value is adjusted for any imbalances between the treatment arms in certain key characteristics. The study design protocol paper can be found on clintrials.gov. The ACT is a well recognised instrument that is used globally in asthma treatment guidelines to assess asthma control. It is self-administered utilising 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all five questions, a patient with asthma can obtain a score that may range between 5 and 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that a patient’s asthma is poorly or not well controlled. A score of 20 to 25 suggests that a patient’s asthma is likely to be well controlled. The total score is calculated as the sum of the scores from all 5 questions, provided all scores are non-missing; if any individual scores are missing then the overall score will be set to missing. A change of 3 points is clinically meaningful for the patient. The Salford Lung Study is intended to enable healthcare professionals and decision makers to more fully assess the potential value of FF/VI by providing data collected in a normal clinical practice setting which is representative of how healthcare professionals and patients may use the medicine in everyday life. It will add to the existing data set from double blind randomised clinical trials (RCTs) for the medicine which, while critical to establishing the safety and efficacy of a medicine, are conducted in a highly controlled environment and enrol a more highly selected patient population than would be expected in everyday clinical care. The study is made possible through a unique collaboration between GSK, North West e-Health (NWEH), The University of Manchester, Salford Royal NHS Foundation Trust, University Hospital of South Manchester (UHSM), NHS Salford and GPs and community pharmacists in Salford, Trafford and South Manchester. The Salford Lung Study in COPD reported findings in May 2016. This is the second of the two Salford Lung Studies to report. Asthma is a chronic lung disease that inflames and narrows the airways. Asthma affects 358 million people worldwide. The causes of asthma are not completely understood but likely involve an interaction between a person’s genetic make-up and the environment. Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta -agonist, in a single inhaler, the Ellipta. Relvar Ellipta is indicated in Europe in the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß -agonist (SABA). Full EU prescribing information is available at: EU Prescribing Information for Relvar Ellipta. FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients. FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician. Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation. Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI. Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease. For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions. An increase in the incidence of pneumonia has been observed in patients with COPD receiving FF/VI. There was also an increased incidence of pneumonias resulting in hospitalisation. In some instances these pneumonia events were fatal. The incidence of pneumonia in patients with asthma was common at the higher dose. In a previous study of FF/VI in asthma the incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo. Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus. Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI. Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures, and pyrexia and muscle spasms..Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). Rare adverse reactions (occurring in >1/10,000 to < 1/1,000) were hypersensitivity reactions (including anaphylaxis, angioedema, rash and urticaria), anxiety, tremor, palpitations, tachycardia and paradoxical bronchospasm. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD. Relvar Ellipta is known as Breo Ellipta in the United States. Breo Ellipta is licensed in the US for: Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta. Innoviva – Innoviva is focused on bringing compelling new medicines to patients in areas of unmet need by leveraging its significant expertise in the development, commercialization and financial management of bio-pharmaceuticals. Innoviva's portfolio is anchored by the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®, which were jointly developed by Innoviva and GSK. Under the agreement with GSK, Innoviva is eligible to receive associated royalty revenues from RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA®. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva's website at www.inva.com. GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com. ANORO, BREO, RELVAR and ELLIPTA are trademarks of the GlaxoSmithKline group of companies. GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Principal risks and uncertainties in the company's Annual Report on Form 20-F for 2016. This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks, uncertainties and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" contained in Innoviva's Annual Report on Form 10-K for the year ended December 31, 2016, which is on file with the U.S. Securities and Exchange Commission (SEC) and available on the SEC's website at www.sec.gov. Additional factors may be described in those sections of Innoviva's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, to be filed with the SEC in the second quarter of 2017. In addition to the risks described above and in Innoviva's other filings with the SEC, other unknown or unpredictable factors also could affect Innoviva's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. (INVA-G).


Study Evaluating Safety and Efficacy of Trappsol® Cyclo™ in a Multi-center European Trial Company Expects Final Data from Trial by End of 2018 ALACHUA, FL--(Marketwired - July 19, 2017) - CTD Holdings, Inc. ( : CTDH), a clinical stage biotechnology company developing cyclodextrin-based products for the treatment of disease, today announced that the first patient has been dosed intravenously in the Company's European Phase I/II clinical trial evaluating Trappsol® Cyclo™ in patients with Niemann-Pick Disease Type C (NPC), a rare and fatal genetic disease that impacts the brain, lung, liver, spleen, and other organs. The first patient was dosed by Dr. Reena Sharma and her team at Salford Royal NHS Foundation Trust in the United Kingdom. Dr. Sharma is Consultant for Adult Metabolic Medicine and Honorary Senior Lecturer at the Mark Holland Metabolic Unit of the Salford NHS Trust, and the Coordinating Investigator for the Phase I/II trial of Trappsol® Cyclo™ in Europe. The first patient visit was supported by NIHR Manchester Clinical Research Facility, which provides 24-hour cover for intensive and complex research studies. "There is currently no treatment available globally for this condition. Those that are available, are limited to delaying the progression of neurological symptoms or providing palliative care to relieve, for example, the gastrointestinal symptoms and seizures," said Dr. Sharma. "We need new treatments that help to address progression of neurological involvement and some of the other problems our patients experience relating to the liver, spleen and lungs. I hope that this study will lead to a new treatment for this devastating condition." The Phase I/II clinical trial, which will include additional sites in the UK and Sweden and is also expected to be expanded to Italy, requires 12 patients to be fully enrolled. The trial will evaluate the safety and efficacy of Trappsol® Cyclo™ in NPC patients ages two and older. Patients will be randomized into three dose groups of 1500 mg/kg, 2000 mg/kg and 2500 mg/kg of Trappsol® Cyclo™ administered via bi-weekly intravenous injections over a period of 48 weeks. "Commencement of dosing of the first patient at the Salford clinical site is another significant milestone for the Company in the development of our Trappsol® Cyclo™," said CTD Chairman and CEO, N. Scott Fine. "We expect final data from this important clinical trial by the end of 2018. CTD remains grateful for the continued support from the many patient families, researchers and clinicians, such as Dr. Sharma, who have helped us reach this important milestone." Trappsol® Cyclo™ is a parenteral grade of hydroxypropyl beta cyclodextrin, a donut-shaped molecule comprised of seven glucopyranose units. To date, intravenous Trappsol® Cyclo™ has been administered to 21 NPC patients worldwide, some for more than six years, via Compassionate Use Programs. Data from treating physicians in the compassionate use program have demonstrated that multiple patients have shown marked improvements in neurological symptoms, lung function or liver morphology, or had stabilization of disease progression, with no significant safety concerns. In addition to the European study, CTD Holdings has initiated a Phase I clinical trial in the U.S. evaluating intravenous administration of Trappsol® Cyclo™ in NPC patients. CTD previously received Fast Track Designation in the U.S. and Orphan Drug Designation for the use of Trappsol® Cyclo™ in the treatment of NPC from the U.S. Food and Drug Administration and the European Medicines Agency. For families interested in learning more about CTD's EU trial or the US trial, please contact CTD's Patient Liaisons: For physicians interested in learning more about the EU trial or the US trial, please contact: About CTD Holdings: CTD Holdings, Inc. is a clinical-stage biotechnology company that develops cyclodextrin-based products for the treatment of disease. The company's Trappsol® Cyclo™, an orphan drug designated product in the United States and Europe, is used to treat Niemann-Pick Disease Type C, a rare and fatal genetic disease. Additional indications for the active ingredient in Trappsol® Cyclo™, are in development. For additional information, visit the company's website: www.ctd-holdings.com Safe Harbor Statement: This press release contains "forward-looking statements" about the company's current expectations about future results, performance, prospects and opportunities. Statements that are not historical facts, such as "anticipates," "believes" and "expects" or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual results in future periods to differ materially from what is expressed in, or implied by, these statements. The factors which may influence the company's future performance include the company's ability to obtain additional capital to expand operations as planned, success in achieving regulatory approval for clinical protocols, enrollment of adequate numbers of patients in clinical trials, unforeseen difficulties in showing efficacy of the company's biopharmaceutical products, success in attracting additional customers and profitable contracts, and regulatory risks associated with producing pharmaceutical grade and food products. These and other risk factors are described from time to time in the company's filings with the Securities and Exchange Commission, including, but not limited to, the company's reports on Forms 10-K and 10-Q. Unless required by law, the company assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.


Patent
University of Manchester and Salford Royal Nhs Foundation Trust | Date: 2016-09-23

A method of selecting data, the method comprising, receiving data indicating a first requirement and identifying first records stored in a first database. The first records relate to first data subjects and the identification is based upon the first requirement. The first data subjects cannot be identified from the records of the first database. Second records are identified, the second records being stored in a second database and relating to the first data subjects. The first data subjects can be identified from the identified records of the second database. Each of the second records corresponds to a respective one of the first records, and the identification of the second records is based upon the first requirement.


LONDON & BRISBANE, Calif.--(BUSINESS WIRE)--GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced positive results from the Salford Lung Study (SLS) in asthma have been simultaneously published in The Lancet journal and presented at the European Respiratory Society (ERS) International Congress in Milan. The innovative study, which reported headline results in May 2017, showed that initiation of once-daily Relvar Ellipta (fluticasone furoate ‘FF’/vilanterol ‘VI’ or ‘FF/VI’, called Breo Ellipta in the U.S.) 92/22mcg or 184/22mcg was superior to usual care in achieving a consistent improvement in patient’s asthma control over the 12 month study duration, measured by the Asthma Control Test (ACT), compared with patients who continued to take their usual care medicines. Improvement was defined as an ACT total score ≥20 or an increase from baseline of ≥3. Statistically significant findings were also seen at 12, 40 and 52 weeks. The study was designed to explore the effectiveness of an asthma medicine when used with minimal intervention in a broad group of people with asthma, closely reflecting how typical asthma patients are managed in everyday clinical care. For the primary endpoint at 24 weeks, a significantly higher percentage of patients with symptomatic asthma and initiated on treatment with FF/VI achieved better control of their asthma (71%), compared with patients continuing usual care treatment (56%), (odds ratio 2.00, 95% CI 1.70, 2.34; p<0.001). Usual care treatment included inhaled corticosteroids (ICS) administered as monotherapy or as ICS/LABA (Long Acting Beta Agonist) combinations. This improvement in asthma control for FF/VI was also consistently seen whether patients were on ICS or ICS/LABA as usual care. Secondary analyses showed that, in addition to better asthma control, patients initiated with FF/VI also achieved higher quality of life scores (as measured by the Asthma Quality-of-Life Questionnaire, AQLQ), and lower impact on their ability to work and take part in activity (as measured by the Work Productivity and Activity Impairment Questionnaire, WPAI): Safety was also assessed and the safety profile of FF/VI in the Salford Lung Study was consistent with the product label for FF/VI. In the study for the intent-to-treat (ITT) population, the incidence of serious adverse events (SAE) was the same in both arms (FF/VI 13% and usual care 13%). Lead Investigator, Ashley Woodcock, Professor of Respiratory Medicine and Clinical Director for Respiratory Medicine, University Hospital of South Manchester and University of Manchester said: “Living with asthma can have a significant effect on people’s day to day life, from sleeping well at night, to doing exercise, and going to work or school. Unfortunately, people with asthma often don’t realise improvements can be made to these parts of their lives. That’s why research, such as the Salford Lung Studies, are important tools to help the medical community manage asthma in a way that has a positive impact for people living with this debilitating condition. We’re delighted the Lancet has published the results of what I believe to be a pioneering study.” This innovative open-label, randomised study, was carried out in 4,233 patients treated by their own General Practitioner in everyday clinical practice. The study had minimal exclusion criteria, minimal intervention, and involved a broad demographic of patients. As such 90% of screened patients were included in the study, making it more representative of everyday clinical practice than traditional randomised control trials. Professor Neil Barnes, Global Medical Head, Respiratory Franchise at GSK said: “The Salford Lung Study Programme is the first of its kind. Whilst we set out to measure the effectiveness of our medicine, Relvar/Breo, in everyday clinical practice, we also wanted to find a way for doctors to more accurately assess how people live and manage their condition on a day to day basis. Through this unique study, we saw a meaningful impact on the daily lives of people managing asthma with FF/VI compared with usual care. Importantly, the results were consistent across the whole 12 months of the study, and when compared to patients continuing either ICS or ICS/LABA as their usual care.” Michael W. Aguiar, President and Chief Executive Officer of Innoviva said: “We are pleased with the results of the Salford Lung Study in asthma that are being presented and published today showing that Relvar Ellipta was superior to usual care treatment in improving asthma control. The Salford Lung Study is important as one of the first clinical effectiveness studies of its kind, providing interesting insights into the management of asthma in clinical care.” The Salford Lung Study is a Phase III multi-centre, open label randomised controlled trial (RCT). The objective of this study was to compare the effectiveness and safety profile of initiating treatment with FF/VI with usual asthma maintenance therapy over a 52 week period. All suitable patients with asthma at 74 primary care sites in and around Salford and South Manchester, UK, were identified from practice databases and invited to participate in the study by their own GP. The primary endpoint of the study was measured at week 24 in the primary effectiveness analysis population. In total, 4,233 patients with asthma who were taking an inhaled corticosteroid (ICS) with or without a long acting beta -agonist (LABA) were randomised to receive either FF/VI or to continue on their existing asthma maintenance therapy (usual care). Usual care was prescribed by the patient's GP and included ICS either alone or in combination with a LABA. In the usual care arm 36% of patients were on an ICS alone and 64% were on an ICS/LABA combination at the time of commencing study medication. The Salford Lung Study had minimal exclusion criteria and involved a broad demographic of patients which allowed a high proportion of patients screened for inclusion into the study, to enter the study (90%). At baseline patients had a mean age of 49.8 (min 18 years) and were split by gender (males vs. female 41/59%). To enrol in the study, patients were required to have a GP diagnosis of asthma as their primary respiratory disease and be receiving maintenance therapy with an ICS with or without LABA for at least 4 weeks prior to visit. At baseline 72% of patients had uncontrolled asthma with an ACT total score of 5 to 19. Patients were followed for a period of 52 weeks in a normal clinical practice setting using their electronic medical record (EMR), linking primary care, secondary care and pharmacy data to collect study data. Throughout the duration of the study physicians were allowed to modify or switch treatment at any point as this would happen in normal clinical practice, the only exception being a switch from usual care to FF/VI. At weeks 12, 24, and 40 patients were telephoned to enquire about whether they had experienced any serious adverse events or non-serious adverse drug reactions. On these telephone calls patients were asked to provide responses to the ACT. At month 12 a face to face visit was carried out. The Standardised Asthma Quality of Life Questionnaire (AQLQ[S]) was also conducted at week 24 and week 52 by telephone. The study team was able to monitor all hospital admissions, outpatient and emergency department visits, as well as data from primary care (including all healthcare contacts, out-of-hours activity and prescriptions of antibiotics or oral steroids) via the electronic health records. The Intent-to-Treat (ITT) population is defined as all patients who have been randomised and received at least one prescription of study medication (e.g., FF/VI or usual asthma maintenance therapy). The primary effectiveness analysis (PEA) population is defined as all ITT patients who have an ACT total score of < 20 at baseline (Randomisation Visit). The odds ratio expressed in the results is calculated as the ratio of the odds of achieving better asthma control as a patient initiated with Relvar Ellipta and the odds of achieving better asthma control as a patient continuing on usual care. This value is adjusted for any imbalances between the treatment arms in certain key characteristics. The study design protocol paper can be found on clintrials.gov. The ACT is a well-recognised instrument that is used globally in asthma management and referenced in treatment guidelines to assess asthma control. It is self-administered utilising 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all five questions, a patient with asthma can obtain a score that may range between 5 and 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that a patient’s asthma is poorly or not well controlled. A score of 20 to 25 suggests that a patient’s asthma is likely to be well controlled. The total score is calculated as the sum of the scores from all 5 questions, provided all scores are non-missing; if any individual scores are missing then the overall score will be set to missing. A change of 3 points is clinically meaningful for the patient. The Salford Lung Study is intended to enable healthcare professionals and decision makers to more fully assess the potential value of FF/VI by providing data collected in a normal clinical practice setting, which is representative of how healthcare professionals and patients may use the medicine in everyday life. It will add to the existing data set from double blind randomised clinical trials (RCTs) for the medicine which, while critical to establishing the safety and efficacy of a medicine, are conducted in a highly controlled environment and enrol a more highly selected patient population than would be expected in everyday clinical care. The study is made possible through a unique collaboration between GSK, North West e-Health (NWEH), The University of Manchester, Salford Royal NHS Foundation Trust, University Hospital of South Manchester (UHSM), NHS Salford and GPs and community pharmacists in Salford, Trafford and South Manchester. The Salford Lung Study in COPD reported findings in May 2016. This is the second of the two Salford Lung Studies to report. Asthma is a chronic lung disease that inflames and narrows the airways. Asthma affects 358 million people worldwide. Despite medical advances, more than half of patients continue to experience poor control and significant symptoms impacting their daily life. The causes of asthma are not completely understood but likely involve an interaction between a person’s genetic make-up and the environment. Key risk factors are inhaled substances that provoke allergic reactions or irritate the airways. Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta -agonist, in a single inhaler, the Ellipta. Relvar Ellipta is indicated in Europe in the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß -agonist (SABA). Full EU prescribing information is available at: EU Prescribing Information for Relvar Ellipta. FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients. FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician. Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation. Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI. Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease. For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions. An increase in the incidence of pneumonia has been observed in patients with COPD receiving FF/VI. There was also an increased incidence of pneumonias resulting in hospitalisation. In some instances these pneumonia events were fatal. The incidence of pneumonia in patients with asthma was common at the higher dose. In a previous study of FF/VI in asthma the incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo. Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus. Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI. Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures, and pyrexia and muscle spasms. Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). Rare adverse reactions (occurring in >1/10,000 to < 1/1,000) were hypersensitivity reactions (including anaphylaxis, angioedema, rash and urticaria), anxiety, tremor, palpitations, tachycardia and paradoxical bronchospasm. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD. Relvar Ellipta is known as Breo Ellipta in the United States. Breo Ellipta is licensed in the US for: Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta. GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com. Trademarks are owned by or licensed to the GSK group of companies. Innoviva – Innoviva is focused on bringing compelling new medicines to patients in areas of unmet need by leveraging its significant expertise in the development, commercialization and financial management of bio-pharmaceuticals. Innoviva's portfolio is anchored by the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®, which were jointly developed by Innoviva and GSK. Under the agreement with GSK, Innoviva is eligible to receive associated royalty revenues from RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA®. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva's website at www.inva.com. GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Principal risks and uncertainties in the company's Annual Report on Form 20-F for 2016. This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events, including the expected use of the data from the Salford Lung Study and the potential benefits thereof. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks, uncertainties and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" contained in Innoviva's Annual Report on Form 10-K for the year ended December 31, 2016 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2017, which are on file with the U.S. Securities and Exchange Commission (SEC) and available on the SEC's website at www.sec.gov. In addition to the risks described above and in Innoviva's other filings with the SEC, other unknown or unpredictable factors also could affect Innoviva's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. (INVA-G).


News Article | September 21, 2017
Site: globenewswire.com

CRANBURY, N.J., Sept. 21, 2017 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD) today announced the U.S. FDA has granted orphan drug designation to ATB200/AT2221 for the treatment of Pompe disease, an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid alpha-glucosidase (GAA). This novel treatment paradigm consists of ATB200, a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures, particularly mannose-6 phosphate (M6P), to enhance uptake, co-administered with AT2221, a pharmacological chaperone. John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, stated, “Today there are significant unmet needs among people living with Pompe, and this orphan drug designation recognizes the potential for ATB200/AT2221 to become a differentiated treatment paradigm for this devastating neuromuscular disease. The initial positive clinical data we have seen to date from our ongoing Phase 1/2 study, including significant improvements in key biomarkers as well as functional outcomes following six months of treatment, are very encouraging. We look forward to announcing new clinical data in all patients from this study at World Muscle Society in early October.” The FDA, through its Office of Orphan Products Development (OOPD), grants orphan status to drugs and biologic products that are intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug designation provides a drug developer with certain benefits and incentives, including a period of marketing exclusivity if regulatory approval is ultimately received for the designated indication. Poster at 22nd International Congress of the World Muscle Society - October 3-7, 2017 Amicus Therapeutics is currently investigating ATB200/AT2221 in a global Phase 1/2 study (ATB200-02) that enrolled 20 patients with Pompe disease. Positive results, including six-month functional outcomes on motor and pulmonary function, were previously reported in the 10 initial patients. Additional data from all patients, including six-month functional outcomes, will be presented at the 22nd International Congress of the World Muscle Society in a late breaker poster (LB.P.3: First-in-Human Study of ATB200/AT2221 in Patients with Pompe Disease: Interim Results from the ATB200-02 Trial (Mark Roberts, Department of Neurology, Salford Royal NHS Foundation Trust)). World Muscle Society will take place October 3-7, 2017 in St. Malo, France. For more information please visit www.wms2017.com. The objectives of the open-label ATB200-02 clinical study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of ATB200/AT2221 over an 18-week primary treatment period followed by a long-term extension. The study enrolled a total of 20 patients across three patient cohorts: ambulatory ERT-switch (Cohort 1, n=11), non-ambulatory ERT-switch (Cohort 2, n=4) and ERT-naïve (Cohort 3, n=5). Patients in Cohort 1 received escalating doses of ATB200 (5, 10, 20 mg/kg), followed by 3 doses of 20 mg/kg ATB200 plus low dose AT2221, followed by ongoing doses of 20 mg/kg ATB200 plus high dose AT2221. Patients in Cohort 2 and 3 patients have all received 20 mg/kg ATB200 plus high dose AT2221. ATB200/AT2221 is a novel treatment paradigm that consists of ATB200, a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures, particularly mannose-6 phosphate (M6P), to enhance uptake, co-administered with AT2221, a pharmacological chaperone. In preclinical studies, ATB200 was associated with increased tissue enzyme levels and reduced glycogen levels in muscle, which was further improved when AT2221 was co-administered with ATB200. Amicus Therapeutics is currently conducting a global Phase 1/2 study (ATB200-02) to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of ATB200/AT2221. Pompe disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid alpha-glucosidase (GAA). Reduced or absent levels of GAA lead to the accumulation of the substrate glycogen in the lysosomes of muscles and other tissues. Signs and symptoms of Pompe disease can be severe and debilitating and include progressive muscle weakness throughout the body, particularly the heart and skeletal muscles. This leads to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. Pompe disease ranges from a rapidly fatal infantile form with severe cardiac involvement to a more slowly progressive, late-onset form primarily affecting skeletal muscle. All forms are characterized by severe muscle weakness that worsens over time. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide. Amicus Therapeutics (Nasdaq:FOLD) is a global biotechnology company at the forefront of therapies for rare and orphan diseases. The Company has a robust pipeline of advanced therapies for a broad range of human genetic diseases. Amicus’ lead programs in development include the small molecule pharmacological chaperone migalastat as a monotherapy for Fabry disease, as well as novel enzyme replacement therapy (ERT) and biologic products for Fabry disease, Pompe disease, and other rare and devastating diseases. This press release contains "forward- looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to encouraging preliminary data from a global Phase 1/2 study to investigate ATB200/AT2221 for the treatment of Pompe and  the potential implications on these data for the future advancement and development of ATB200/AT2221. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” "confidence," "encouraged," “potential,” “plan,” “targets,” “likely,” “may,” “will,” “would,” “should” and “could,” and similar expressions or words identify forward-looking statements. The forward looking statements included in this press release are based on management's current expectations and belief's which are subject to a number of risks, uncertainties and factors,  including that the preliminary data based on a small patient sample and reported before completion of the study  will not  be predictive of future results,  that results of additional preliminary data or data from  the completed study or any future study will not yield results that are consistent with the preliminary data presented, that the Company will be not  able to demonstrate the safety and efficacy of ATB200/AT2221, that later  study results will not support  further development, or even if such later  results are favorable, that the Company will not be able to  successfully complete the development of, obtain regulatory approval for, or successfully commercialize  ATB200/AT2221.  In addition, all forward looking statements are subject to the other risks and uncertainties detailed in our Annual Report on Form 10-K for the year ended December 31, 2016 and Quarterly Report on 10-Q for the Quarter ended June 30, 2017.  As a consequence, actual results may differ materially from those set forth in this press release.  You are cautioned not to place undue reliance on these forward looking statements, which speak only of the date hereof.  All forward looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise this press release to reflect events or circumstances after the date hereof.


Murray K.N.,University of Manchester | Parry-Jones A.R.,Salford Royal NHS Foundation Trust | Allan S.M.,University of Manchester
Frontiers in Cellular Neuroscience | Year: 2015

Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. © 2015 Murray, Parry-Jones and Allan.


DURHAM, N.C., March 1, 2017 /PRNewswire/ -- The Salford Royal NHS Foundation Trust of the National Health Service (NHS), one of the most innovative and digitally-advanced Trusts in the United Kingdom (UK), has announced a partnership with Validic, the industry's leading data connectivity...


Winter-Roach B.A.,Salford Royal NHS Foundation Trust
Cochrane database of systematic reviews (Online) | Year: 2012

Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women). One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution. Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.

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