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


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.


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.


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.


Krogsboll L.T.,Rigshospitalet
Cochrane database of systematic reviews (Online) | Year: 2012

General health checks are common elements of health care in some countries. These aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is, therefore, important to assess whether general health checks do more good than harm. We aimed to quantify the benefits and harms of general health checks with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes such as blood pressure and serum cholesterol levels. We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register, MEDLINE, EMBASE, Healthstar, CINAHL, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) to July 2012. Two authors screened titles and abstracts, assessed papers for eligibility and read reference lists. One author used citation tracking (Web of Knowledge) and asked trialists about additional studies. We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening general populations for more than one disease or risk factor in more than one organ system. Two authors independently extracted data and assessed the risk of bias in the trials. We contacted authors for additional outcomes or trial details when necessary. For mortality outcomes we analysed the results with random-effects model meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. We included 16 trials, 14 of which had available outcome data (182,880 participants). Nine trials provided data on total mortality (155,899 participants, 11,940 deaths), median follow-up time nine years, giving a risk ratio of 0.99 (95% confidence interval (CI) 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (152,435 participants, 4567 deaths), risk ratio 1.03 (95% CI 0.91 to 1.17) and eight trials on cancer mortality (139,290 participants, 3663 deaths), risk ratio 1.01 (95% CI 0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings.We did not find an effect on clinical events or other measures of morbidity but one trial found an increased occurrence of hypertension and hypercholesterolaemia with screening and one trial found an increased occurence of self-reported chronic disease. One trial found a 20% increase in the total number of new diagnoses per participant over six years compared to the control group. No trials compared the total number of prescriptions, but two out of four trials found an increased number of people using antihypertensive drugs. Two out of four trials found small beneficial effects on self-reported health, but this could be due to reporting bias as the trials were not blinded. We did not find an effect on admission to hospital, disability, worry, additional visits to the physician, or absence from work, but most of these outcomes were poorly studied. We did not find useful results on the number of referrals to specialists, the number of follow-up tests after positive screening results, or the amount of surgery. General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although the number of new diagnoses was increased. Important harmful outcomes, such as the number of follow-up diagnostic procedures or short term psychological effects, were often not studied or reported and many trials had methodological problems. With the large number of participants and deaths included, the long follow-up periods used, and considering that cardiovascular and cancer mortality were not reduced, general health checks are unlikely to be beneficial.


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.


Patent
Rigshospitalet and Technical University of Denmark | Date: 2015-12-14

The present invention is directed to the technical field of imaging compositions useful for diagnosing cancer and other diseases in a subject. In particular, the invention relates to a class of diagnostic compounds comprising a novel liposome composition with encapsulated metal entities such as radionuclides, for example ^(61)Cu and ^(64)Cu copper isotopes. The invention further relates to a novel method for loading delivery systems, such as liposome compositions, with metal entities such as radionuclides, and the use of liposomes for targeted diagnosis and treatment of a target site, such as cancerous tissue and, in general, pathological conditions associated with leaky blood vessels. The present invention provides a new diagnostic tool for the utilization of positron emission tomography (PET) imaging technique.

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