Rigshospitalet

Copenhagen, Denmark

Rigshospitalet

Copenhagen, Denmark
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The combined positive outcome of the results from the clinical phase IIa CHIC (Copenhagen Head Injury Cyclosporine) study, conducted at Rigshospitalet in Copenhagen, Denmark, and the preclinical studies, done in collaboration with the University of Pennsylvania (Penn), USA, have now convinced NeuroVive to proceed into the next stage of clinical development. The company has therefore decided to close the CHIC study in advance and focus its TBI project efforts on preparing for the next clinical study with NeuroSTAT for TBI. The results of the open label CHIC study show that appropriate dose-dependent concentration levels can be measured in the blood, and that NeuroSTAT reaches the target, the central nervous system (CNS). No unexpected safety signals were detected. Thus, the primary objective of CHIC to demonstrate safety and elucidate pharmacokinetics of NeuroSTAT at two different dose levels (5 and 10 mg/kg/day) in patients with severe TBI has been reached. A significantly reduced volume of brain injury (35% decrease) after NeuroSTAT treatment was observed in MRI scans in the experimental TBI studies done in collaboration with Penn. Furthermore, these studies displayed positive changes in brain energy metabolite levels and mitochondrial respiratory function, as well as decreased generation of reactive oxygen species. "The NeuroSTAT effects observed in our state-of-the art experimental model for TBI are very promising. Our collaborative approach on preclinical study design will set a completely novel standard in the development of new drugs in the field", said Susan Margulies, PhD, Professor in the Department of Bioengineering at the University of Pennsylvania, US, and lead investigator for the preclinical studies. "The positive results are important milestones for the NeuroSTAT clinical development program. We now have the data we need to move forward to the next phase in the clinical development. We want to thank all site staff, caregivers, patients and families at Rigshospitalet in Copenhagen for their valuable contribution to this project. Also, we wish to thank the team at Penn for a very fruitful collaboration that has given very important scientific support to the NeuroSTAT clinical program", said Erik Kinnman, CEO at NeuroVive. "With the decision to move forward with the TBI program, the company's project portfolio have matured further and the approach of protecting the mitochondria in TBI with NeuroSTAT is validated by the new data. Importantly, we are about to take another step towards developing a medicine to patients with TBI, which is an area of high unmet medical need", he continued. NeuroVive has initiated preparatory activities for the continued clinical development program. Next step is discussions with regulatory authorities in Europe and the US regarding the findings in the clinical and experimental studies, as well as the design of the next clinical study (Phase IIb proof of concept). Additionally, study preparations such as production of investigational medicinal product, approval of the clinical trial application, IND approval, ethics committee approval etc. need to be completed before study start. About the Phase IIa clinical study, CHIC at Rigshospitalet in Copenhagen The phase II CHIC (Copenhagen Head Injury Ciclosporin) study was an open label study. The primary objective with the study was to establish safety and to characterize the pharmacokinetic profile of two dosing regimens of NeuroSTAT in severe Traumatic Brain Injury (TBI) patients. In addition, exploratory measurements to evaluate the efficacy of NeuroSTAT at mitochondrial level, and study how NeuroSTAT affects various biochemical processes after a brain injury, are being processed Principal Investigator for the study is Jesper Kelsen, MD, PhD, Specialist in Neurosurgery, Department of Neurosurgery, Rigshospitalet, Copenhagen University Hospital. About the TBI experimental studies at the University of Pennsylvania (Penn) In collaboration with Penn, NeuroVive has evaluated the effect of NeuroSTAT in a non-clinical experimental TBI model. A total of three substudies have successfully been conducted and completed. Positive results from the first two substudies established the pharmacokinetic profile of NeuroSTAT in blood, CSF and brain in the disease model, and showed that NeuroSTAT dose-dependently crosses the blood-brain barrier. The third and final sub study evaluated several different efficacy parameters related to mitochondrial function and metabolism, as well as advanced translational brain imaging MR techniques important in the design of the next clinical study. Further analyses are ongoing and additional data will be presented at the 7th Annual Traumatic Brain Injury Conference in Washington, DC, US on 24-25 May and at the Annual National Neurotrauma Symposium, Neurotrauma 2017, in Snowbird, Utah, US, on 9-12 July 2017. Traumatic brain injury (TBI) is caused by external violence to the head resulting in immediate damage to nerve cells. The damage continues to worsen for several days after the trauma, which in many cases has a significantly negative effect on the overall injury. At present, there are no approved treatments for the prevention of these secondary injuries. In the US, some 2.2 million people are affected annually, causing more than 50,000 deaths and 280,000 hospitalizations. The direct and indirect costs associated with TBI are an estimated USD 60 billion, and a large number of patients suffer moderate to severe functional disabilities requiring intensive care and various forms of support (www.nih.gov). The aim is that better preventive therapies for secondary brain damage, such as NeuroSTAT, will lead to higher survival rates, and significantly improve quality of life and neurological function of patients post-TBI. NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine. The company is committed to the discovery and development of medicines that preserve mitochondrial integrity and function in areas of unmet medical need. The company's strategy is to advance drugs for rare diseases through clinical development and into the market. The strategy for projects within larger indications outside the core focus area is out-licensing in the preclinical phase. NeuroVive enhances the value of its projects in an organization that includes strong international partnerships and a network of mitochondrial research institutions, as well as expertise with capacities within drug development and production. NeuroVive has a project in early clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project entering clinical phase I (KL1333). NeuroSTAT has orphan drug designation in Europe and in the US. The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. NeuroVive is listed on Nasdaq Stockholm, Sweden (ticker: NVP). The share is also traded on the OTCQX Best Market in the US (OTC: NEVPF). For investor relations and media questions, please contact: This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CEST on 23 May 2017. This information was brought to you by Cision http://news.cision.com http://news.cision.com/neurovive-pharmaceutical/r/neurovive-to-continue-neurostat--clinical-development-after-positive-outcome-in-preclinical-and-clin,c2271790 The following files are available for download:


NeuroVive Pharmaceutical AB(Nasdaq Stockholm: NVP, OTCQX: NEVPF) today announced positive results from clinical and preclinical studies with its drug NeuroSTAT® for the prevention of the sequelae of traumatic brain injury (TBI). The company is now preparing for the next clinical study with NeuroSTAT for TBI. The combined positive outcome of the results from the clinical phase IIa CHIC (Copenhagen Head Injury Cyclosporine) study, conducted at Rigshospitalet in Copenhagen, Denmark, and the preclinical studies, done in collaboration with the University of Pennsylvania (Penn), USA, have now convinced NeuroVive to proceed into the next stage of clinical development. The company has therefore decided to close the CHIC study in advance and focus its TBI project efforts on preparing for the next clinical study with NeuroSTAT for TBI. The results of the open label CHIC study show that appropriate dose-dependent concentration levels can be measured in the blood, and that NeuroSTAT reaches the target, the central nervous system (CNS). No unexpected safety signals were detected. Thus, the primary objective of CHIC to demonstrate safety and elucidate pharmacokinetics of NeuroSTAT at two different dose levels (5 and 10 mg/kg/day) in patients with severe TBI has been reached. A significantly reduced volume of brain injury (35% decrease) after NeuroSTAT treatment was observed in MRI scans in the experimental TBI studies done in collaboration with Penn. Furthermore, these studies displayed positive changes in brain energy metabolite levels and mitochondrial respiratory function, as well as decreased generation of reactive oxygen species. "The NeuroSTAT effects observed in our state-of-the art experimental model for TBI are very promising. Our collaborative approach on preclinical study design will set a completely novel standard in the development of new drugs in the field", said Susan Margulies, PhD, Professor in the Department of Bioengineering at the University of Pennsylvania, US, and lead investigator for the preclinical studies. "The positive results are important milestones for the NeuroSTAT clinical development program. We now have the data we need to move forward to the next phase in the clinical development. We want to thank all site staff, caregivers, patients and families at Rigshospitalet in Copenhagen for their valuable contribution to this project. Also, we wish to thank the team at Penn for a very fruitful collaboration that has given very important scientific support to the NeuroSTAT clinical program", said Erik Kinnman, CEO at NeuroVive. "With the decision to move forward with the TBI program, the company's project portfolio have matured further and the approach of protecting the mitochondria in TBI with NeuroSTAT is validated by the new data. Importantly, we are about to take another step towards developing a medicine to patients with TBI, which is an area of high unmet medical need", he continued. NeuroVive has initiated preparatory activities for the continued clinical development program. Next step is discussions with regulatory authorities in Europe and the US regarding the findings in the clinical and experimental studies, as well as the design of the next clinical study (Phase IIb proof of concept). Additionally, study preparations such as production of investigational medicinal product, approval of the clinical trial application, IND approval, ethics committee approval etc. need to be completed before study start. About the Phase IIa clinical study, CHIC at Rigshospitalet in Copenhagen The phase II CHIC (Copenhagen Head Injury Ciclosporin) study was an open label study. The primary objective with the study was to establish safety and to characterize the pharmacokinetic profile of two dosing regimens of NeuroSTAT in severe Traumatic Brain Injury (TBI) patients. In addition, exploratory measurements to evaluate the efficacy of NeuroSTAT at mitochondrial level, and study how NeuroSTAT affects various biochemical processes after a brain injury, are being processed Principal Investigator for the study is Jesper Kelsen, MD, PhD, Specialist in Neurosurgery, Department of Neurosurgery, Rigshospitalet, Copenhagen University Hospital. About the TBI experimental studies at the University of Pennsylvania (Penn) In collaboration with Penn, NeuroVive has evaluated the effect of NeuroSTAT in a non-clinical experimental TBI model. A total of three substudies have successfully been conducted and completed. Positive results from the first two substudies established the pharmacokinetic profile of NeuroSTAT in blood, CSF and brain in the disease model, and showed that NeuroSTAT dose-dependently crosses the blood-brain barrier. The third and final sub study evaluated several different efficacy parameters related to mitochondrial function and metabolism, as well as advanced translational brain imaging MR techniques important in the design of the next clinical study. Further analyses are ongoing and additional data will be presented at the 7th Annual Traumatic Brain Injury Conference in Washington, DC, US on 24-25 May and at the Annual National Neurotrauma Symposium, Neurotrauma 2017, in Snowbird, Utah, US, on 9-12 July 2017. Traumatic brain injury (TBI) is caused by external violence to the head resulting in immediate damage to nerve cells. The damage continues to worsen for several days after the trauma, which in many cases has a significantly negative effect on the overall injury. At present, there are no approved treatments for the prevention of these secondary injuries. In the US, some 2.2 million people are affected annually, causing more than 50,000 deaths and 280,000 hospitalizations. The direct and indirect costs associated with TBI are an estimated USD 60 billion, and a large number of patients suffer moderate to severe functional disabilities requiring intensive care and various forms of support (www.nih.gov). The aim is that better preventive therapies for secondary brain damage, such as NeuroSTAT, will lead to higher survival rates, and significantly improve quality of life and neurological function of patients post-TBI. NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine. The company is committed to the discovery and development of medicines that preserve mitochondrial integrity and function in areas of unmet medical need. The company's strategy is to advance drugs for rare diseases through clinical development and into the market. The strategy for projects within larger indications outside the core focus area is out-licensing in the preclinical phase. NeuroVive enhances the value of its projects in an organization that includes strong international partnerships and a network of mitochondrial research institutions, as well as expertise with capacities within drug development and production. NeuroVive has a project in early clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project entering clinical phase I (KL1333). NeuroSTAT has orphan drug designation in Europe and in the US. The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. NeuroVive is listed on Nasdaq Stockholm, Sweden (ticker: NVP). The share is also traded on the OTCQX Best Market in the US (OTC: NEVPF). For investor relations and media questions, please contact: This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CEST on 23 May 2017. This information was brought to you by Cision http://news.cision.com http://news.cision.com/neurovive-pharmaceutical/r/neurovive-to-continue-neurostat--clinical-development-after-positive-outcome-in-preclinical-and-clin,c2271790 The following files are available for download:


The combined positive outcome of the results from the clinical phase IIa CHIC (Copenhagen Head Injury Cyclosporine) study, conducted at Rigshospitalet in Copenhagen, Denmark, and the preclinical studies, done in collaboration with the University of Pennsylvania (Penn), USA, have now convinced NeuroVive to proceed into the next stage of clinical development. The company has therefore decided to close the CHIC study in advance and focus its TBI project efforts on preparing for the next clinical study with NeuroSTAT for TBI. The results of the open label CHIC study show that appropriate dose-dependent concentration levels can be measured in the blood, and that NeuroSTAT reaches the target, the central nervous system (CNS). No unexpected safety signals were detected. Thus, the primary objective of CHIC to demonstrate safety and elucidate pharmacokinetics of NeuroSTAT at two different dose levels (5 and 10 mg/kg/day) in patients with severe TBI has been reached. A significantly reduced volume of brain injury (35% decrease) after NeuroSTAT treatment was observed in MRI scans in the experimental TBI studies done in collaboration with Penn. Furthermore, these studies displayed positive changes in brain energy metabolite levels and mitochondrial respiratory function, as well as decreased generation of reactive oxygen species. "The NeuroSTAT effects observed in our state-of-the art experimental model for TBI are very promising. Our collaborative approach on preclinical study design will set a completely novel standard in the development of new drugs in the field", said Susan Margulies, PhD, Professor in the Department of Bioengineering at the University of Pennsylvania, US, and lead investigator for the preclinical studies. "The positive results are important milestones for the NeuroSTAT clinical development program. We now have the data we need to move forward to the next phase in the clinical development. We want to thank all site staff, caregivers, patients and families at Rigshospitalet in Copenhagen for their valuable contribution to this project. Also, we wish to thank the team at Penn for a very fruitful collaboration that has given very important scientific support to the NeuroSTAT clinical program", said Erik Kinnman, CEO at NeuroVive. "With the decision to move forward with the TBI program, the company's project portfolio have matured further and the approach of protecting the mitochondria in TBI with NeuroSTAT is validated by the new data. Importantly, we are about to take another step towards developing a medicine to patients with TBI, which is an area of high unmet medical need", he continued. NeuroVive has initiated preparatory activities for the continued clinical development program. Next step is discussions with regulatory authorities in Europe and the US regarding the findings in the clinical and experimental studies, as well as the design of the next clinical study (Phase IIb proof of concept). Additionally, study preparations such as production of investigational medicinal product, approval of the clinical trial application, IND approval, ethics committee approval etc. need to be completed before study start. About the Phase IIa clinical study, CHIC at Rigshospitalet in Copenhagen The phase II CHIC (Copenhagen Head Injury Ciclosporin) study was an open label study. The primary objective with the study was to establish safety and to characterize the pharmacokinetic profile of two dosing regimens of NeuroSTAT in severe Traumatic Brain Injury (TBI) patients. In addition, exploratory measurements to evaluate the efficacy of NeuroSTAT at mitochondrial level, and study how NeuroSTAT affects various biochemical processes after a brain injury, are being processed Principal Investigator for the study is Jesper Kelsen, MD, PhD, Specialist in Neurosurgery, Department of Neurosurgery, Rigshospitalet, Copenhagen University Hospital. About the TBI experimental studies at the University of Pennsylvania (Penn) In collaboration with Penn, NeuroVive has evaluated the effect of NeuroSTAT in a non-clinical experimental TBI model. A total of three substudies have successfully been conducted and completed. Positive results from the first two substudies established the pharmacokinetic profile of NeuroSTAT in blood, CSF and brain in the disease model, and showed that NeuroSTAT dose-dependently crosses the blood-brain barrier. The third and final sub study evaluated several different efficacy parameters related to mitochondrial function and metabolism, as well as advanced translational brain imaging MR techniques important in the design of the next clinical study. Further analyses are ongoing and additional data will be presented at the 7th Annual Traumatic Brain Injury Conference in Washington, DC, US on 24-25 May and at the Annual National Neurotrauma Symposium, Neurotrauma 2017, in Snowbird, Utah, US, on 9-12 July 2017. Traumatic brain injury (TBI) is caused by external violence to the head resulting in immediate damage to nerve cells. The damage continues to worsen for several days after the trauma, which in many cases has a significantly negative effect on the overall injury. At present, there are no approved treatments for the prevention of these secondary injuries. In the US, some 2.2 million people are affected annually, causing more than 50,000 deaths and 280,000 hospitalizations. The direct and indirect costs associated with TBI are an estimated USD 60 billion, and a large number of patients suffer moderate to severe functional disabilities requiring intensive care and various forms of support (www.nih.gov). The aim is that better preventive therapies for secondary brain damage, such as NeuroSTAT, will lead to higher survival rates, and significantly improve quality of life and neurological function of patients post-TBI. NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine. The company is committed to the discovery and development of medicines that preserve mitochondrial integrity and function in areas of unmet medical need. The company's strategy is to advance drugs for rare diseases through clinical development and into the market. The strategy for projects within larger indications outside the core focus area is out-licensing in the preclinical phase. NeuroVive enhances the value of its projects in an organization that includes strong international partnerships and a network of mitochondrial research institutions, as well as expertise with capacities within drug development and production. NeuroVive has a project in early clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project entering clinical phase I (KL1333). NeuroSTAT has orphan drug designation in Europe and in the US. The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. NeuroVive is listed on Nasdaq Stockholm, Sweden (ticker: NVP). The share is also traded on the OTCQX Best Market in the US (OTC: NEVPF). For investor relations and media questions, please contact: This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CEST on 23 May 2017. This information was brought to you by Cision http://news.cision.com http://news.cision.com/neurovive-pharmaceutical/r/neurovive-to-continue-neurostat--clinical-development-after-positive-outcome-in-preclinical-and-clin,c2271790 The following files are available for download: To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/neurovive-to-continue-neurostat-clinical-development-after-positive-outcome-in-preclinical-and-clinical-tbi-studies-300462058.html


There is provided a novel conjugate that binds to the cell surface receptor uPA (uPAR). The conjugate is based on a fluorescence-labeled peptide useful as a diagnostic probe to the surfaces of cells expressing uPAR. The conjugate is capable of carrying a suitable detectable and imageable label that will allow qualitative detection and also quantitation of uPAR levels in vitro and in vivo. This renders the surgical resection of tumors more optimal.


News Article | May 9, 2017
Site: news.yahoo.com

Having low body mass index (BMI) does not increase people's risk of developing Alzheimer's disease, scientists have said. Instead, people may go on to lose weight once they are diagnosed, as their behaviours, appetite and sense of smell are modified. The study, published in the Journal of Clinical Endocrinology & Metabolism, looks at blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS) – 645 of whom developed Alzheimer's disease. Trending: Wild dolphins' immune systems are failing because of ocean pollution What is the Body Mass Index? The Body Mass Index (BMI) is used to quickly and simply assess a person's weight in regard to their height. It is calculated using the following formula: BMI (kg/m2) = mass (kg) / height (m)2 Previous research using data recorded from more than two million people in the UK had established that low BMI is associated with a heightened risk of Alzheimer's disease. Here, the researchers wanted to put these findings to a test. Most popular: Is your baby in pain? Brain scan can detect physical suffering in infants Instead of looking merely for associations, they went a step further and conducted what is known as "Mendelian randomisation analysis". This involved examining the participants' DNA for the presence of five genetic variants that are known to have a strong association with BMI. On top of the Copenhagen General Population Study, the scientists also used data from up to 249,796 individuals participating in the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Based on how many variants they had, all the participants were divided into four groups reflecting the likelihood of low BMI. The scientists then assessed the risk of developing Alzheimer's disease for each of these groups. "When we simply look at observational associations, we find the same as other previous studies. A low BMI is statistically linked to a higher risk of Alzheimer's. However, association does not mean causality", the study's senior author, Ruth Frikke-Schmidt, Chief Physician at Rigshospitalet in Copenhagen, told IBTimes UK. "Because genetic variants associated with low BMI are life-long and acquired totally randomly, it is a clean measurement of low BMI. It's good to use as a test of causality for body mass index". The researchers found that having genetic variants associated with low BMI did not increase the risk of Alzheimer's disease. Alzheimer's Society Research Communications Officer Dr Louise Walker commented:"Researching the links between BMI, weight and Alzheimer's disease is often complicated and findings are often contradictory. This research is a first step to untangle this complexity. "We need more large studies like this as they can tell us what patterns we need to investigate. The main limitation here however is that the scientists do not take into account in their analysis people who might have a low BMI for other reasons than genetic predispositions". The authors nevertheless came up with an explanation for the link observed between low BMI and the disease. They propose that patients' low BMI is due to behavioural changes, and appetite and weight loss they may suffer from in the early stages of the disease. Increasing people's BMI would probably have no impact on their risk of developing the disease. "The present research is important since it concludes that the association between low BMI and Alzheimer's disease is not of a causal nature. Changing public health recommendations based on observational data alone would cause more harm than benefits", Frikke-Schmidt concluded. You may be interested in:


Patent
Rigshospitalet, Copenhagen University and University of Southern Denmark | Date: 2017-01-06

The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.


News Article | May 9, 2017
Site: www.eurekalert.org

WASHINGTON--A new large-scale genetic study found that low body mass index (BMI) is likely not a causal risk factor for Alzheimer's disease, as earlier research had suggested, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. "Although prior studies found an association between Alzheimer's disease and low BMI, the new findings suggest this is not a causal relationship," said the study's senior author, Ruth Frikke-Schmidt, M.D., D.M.Sc., Ph.D., Chief Physician at Rigshospitalet in Copenhagen, Denmark, and Associate Research Professor at the University of Copenhagen. "The association can likely be explained by the fact that individuals with Alzheimer's disease are more likely to have low BMIs due to loss of appetite and weight loss in the early stages of the disease." More than 5 million Americans have Alzheimer's disease, according to the Alzheimer's Association's 2017 Alzheimer's Disease Facts and Figures Report. The disease affects the brain and is a common form of dementia. It is the sixth leading cause of death in the United States. To examine the association between Alzheimer's disease and low BMI, the researchers analyzed blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS). Of the participants, 645 individuals developed Alzheimer's disease. The researchers analyzed the study participants' DNA for the presence of five genetic variants that have strong associations with BMI. Based on how many variants were found, participants were divided into four groups to reflect the likelihood of low BMI. The researchers also analyzed data from up to 249,796 individuals participating in the Genetic Investigation of ANthropometric Traits (GIANT) consortium for the genetic variants closely linked to low BMI. The analysis found the presence of the genetic variants tied to low BMI was not associated with increased risk of Alzheimer's disease. For comparison, the researchers examined if individuals with genetic variants connected to high BMI were more likely to have type 2 diabetes and did find the expected causal relationship. "We found individuals with lifelong low BMI due to genetic variation were not at increased risk of Alzheimer's disease," Frikke-Schmidt said. "Since genetic variants are not affected by other risk factors or diseases, this is a clean measure that can help to determine causality. The findings highlight that testing causality of a risk factor is pivotal before considering changing public health recommendations based on observational data alone." Other authors of the study include: Liv Tybjærg Nordestgaard and Anne Tybjærg-Hansen, of Rigshospitalet; and Børge G. Nordestgaard, of Herlev and Gentofte Hospital. All three also are affiliated with the University of Copenhagen. The research was supported by the Danish Medical Research Council, the Lundbeck Foundation, the Alzheimer Research Foundation, and the Research Fund at the Capital Region of Denmark. The study, "Body Mass Index and Risk of Alzheimer Disease: a Mendelian Randomization Study of 399,536 Individuals," will be published online at https:/ , ahead of print. Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions. The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www. . Follow us on Twitter at @TheEndoSociety and @EndoMedia.


Lundh A.,Rigshospitalet
Cochrane database of systematic reviews (Online) | Year: 2012

Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. This review is an update using more stringent methodology and also investigating sponsorship of device studies. To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. We searched MEDLINE (1948 to September 2010), EMBASE (1980 to September 2010), the Cochrane Methodology Register (Issue 4, 2010) and Web of Science (August 2011). In addition, we searched reference lists of included papers, previous systematic reviews and author files. Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions. Two assessors identified potentially relevant papers, and a decision about final inclusion was made by all authors. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals). Forty-eight papers were included. Industry sponsored studies more often had favorable efficacy results, risk ratio (RR): 1.24 (95% confidence interval (CI): 1.14 to 1.35), harms results RR: 1.87 (95% CI: 1.54 to 2.27) and conclusions RR: 1.31 (95% CI: 1.20 to 1.44) compared with non-industry sponsored studies. Ten papers reported on sponsorship and effect size, but could not be pooled due to differences in their reporting of data. The results were heterogeneous; five papers found larger effect sizes in industry sponsored studies compared with non-industry sponsored studies and five papers did not find a difference in effect size. Only two papers (including 120 device studies) reported separate data for devices and we did not find a difference between drug and device studies on the association between sponsorship and conclusions (test for interaction, P = 0.23). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment and follow-up. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.32 (95% CI: 1.05 to 1.65), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.84 (95% CI: 0.70 to 1.01). Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.


Thomsen T.,Rigshospitalet
The Cochrane database of systematic reviews | Year: 2014

Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. The objectives of this review are to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively, and on the incidence of postoperative complications. We searched the Cochrane Tobacco Addiction Group Specialized Register in January 2014. Randomized controlled trials that recruited people who smoked prior to surgery, offered a smoking cessation intervention, and measured preoperative and long-term abstinence from smoking or the incidence of postoperative complications or both outcomes. The review authors independently assessed studies to determine eligibility, and discussed the results between them. Thirteen trials enrolling 2010 participants met the inclusion criteria. One trial did not report cessation as an outcome. Seven reported some measure of postoperative morbidity. Most studies were judged to be at low risk of bias but the overall quality of evidence was moderate due to the small number of studies contributing to each comparison.Ten trials evaluated the effect of behavioural support on cessation at the time of surgery; nicotine replacement therapy (NRT) was offered or recommended to some or all participants in eight of these. Two trials initiated multisession face-to-face counselling at least four weeks before surgery and were classified as intensive interventions, whilst seven used a brief intervention. One further study provided an intensive intervention to both groups, with the intervention group additionally receiving a computer-based scheduled reduced smoking intervention. One placebo-controlled trial examined the effect of varenicline administered one week preoperatively followed by 11 weeks postoperative treatment, and one placebo-controlled trial examined the effect of nicotine lozenges from the night before surgery as an adjunct to brief counselling at the preoperative evaluation. There was evidence of heterogeneity between the effects of trials using intensive and brief interventions, so we pooled these separately. An effect on cessation at the time of surgery was apparent in both subgroups, but the effect was larger for intensive intervention (pooled risk ratio (RR) 10.76; 95% confidence interval (CI) 4.55 to 25.46, two trials, 210 participants) than for brief interventions (RR 1.30; 95% CI 1.16 to 1.46, 7 trials, 1141 participants). A single trial did not show evidence of benefit of a scheduled reduced smoking intervention. Neither nicotine lozenges nor varenicline were shown to increase cessation at the time of surgery but both had wide confidence intervals (RR 1.34; 95% CI 0.86 to 2.10 (1 trial, 46 participants) and RR 1.49; 95% CI 0.98 to 2.26 (1 trial, 286 participants) respectively). Four of these trials evaluated long-term smoking cessation and only the intensive intervention retained a significant effect (RR 2.96; 95% CI 1.57 to 5.55, 2 trials, 209 participants), whilst there was no evidence of a long-term effect following a brief intervention (RR 1.09; 95% CI 0.68 to 1.75, 2 trials, 341 participants). The trial of varenicline did show a significant effect on long-term smoking cessation (RR 1.45; 95% CI 1.01 to 2.07, 1 trial, 286 participants).Seven trials examined the effect of smoking intervention on postoperative complications. As with smoking outcomes, there was evidence of heterogeneity between intensive and brief behavioural interventions. In subgroup analyses there was a significant effect of intensive intervention on any complications (RR 0.42; 95% CI 0.27 to 0.65, 2 trials, 210 participants) and on wound complications (RR 0.31; 95% CI 0.16 to 0.62, 2 trials, 210 participants). For brief interventions, where the impact on smoking had been smaller, there was no evidence of a reduction in complications (RR 0.92; 95% CI 0.72 to 1.19, 4 trials, 493 participants) for any complication (RR 0.99; 95% CI 0.70 to 1.40, 3 trials, 325 participants) for wound complications. The trial of varenicline did not detect an effect on postoperative complications (RR 0.94; 95% CI 0.52 to 1.72, 1 trial, 286 participants). There is evidence that preoperative smoking interventions providing behavioural support and offering NRT increase short-term smoking cessation and may reduce postoperative morbidity. One trial of varenicline begun shortly before surgery has shown a benefit on long-term cessation but did not detect an effect on early abstinence or on postoperative complications. The optimal preoperative intervention intensity remains unknown. Based on indirect comparisons and evidence from two small trials, interventions that begin four to eight weeks before surgery, include weekly counselling and use NRT are more likely to have an impact on complications and on long-term smoking cessation.


The present invention relates to a novel use and methods of treatment using sympathicomimetic agonists with pro-hemostatic activity.

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