Connolly S.J.,Hamilton Health Sciences |
Eikelboom J.,Hamilton Health Sciences |
Joyner C.,University of Toronto |
Diener H.-C.,University of Duisburg - Essen |
And 27 more authors.
New England Journal of Medicine | Year: 2011
BACKGROUND: Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. METHODS: In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism. RESULTS: Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P = 0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P = 0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups. CONCLUSIONS: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. Copyright © 2011 Massachusetts Medical Society.
News Article | October 31, 2016
Treatment Effect of AC5-Significantly Shortening of Time To Hemostasis vs Control- Was Consistent Whether Patients Were Taking Antiplatelet Therapy or Not FRAMINGHAM, MA--(Marketwired - Oct 31, 2016) - Arch Therapeutics, Inc. ( : ARTH) ("Arch" or the "Company"), developer of devices for use in controlling bleeding and fluid loss in order to provide faster and safer surgical and interventional care, reports additional positive data in its recently completed single-center, randomized, single-blind prospective clinical study (NCT 02704104) of the AC5 Topical Hemostatic Device™ ("AC5™") in skin lesion patients with bleeding wounds. On August 15, 2016, the Company reported top-line data from the clinical study that indicated that AC5 was safe and that it reduced time to hemostasis in wounds versus controls. Today, the Company released the results of additional analysis of the subgroup of 10 patients who were taking a prescribed antiplatelet medication, commonly known as a blood thinner, such as aspirin, which indicated that AC5 had similar effects for the subgroup of patients taking an antiplatelet agent. In particular, in this newly reported analysis of the primary and secondary outcomes for wounds among patients treated with an antiplatelet agent, the primary objective of safety throughout the surgical procedure and until the end of a 30-day follow-up period post procedure was met and AC5 was well tolerated. Moreover, AC5 shortened time to hemostasis ("TTH") versus a control whether or not patients were taking antiplatelet therapy, suggesting that AC5 performance is not affected by antiplatelet therapy. The reduced median TTH of the AC5 treated wounds versus the control wounds was statistically significant for both the overall group of 46 patients (p<0.001) and for the subgroup of 10 patients on antiplatelet therapy (p=0.005). Further, the median TTH for wounds treated with AC5 was less than 30 seconds for both the overall study group and for the subset of patients taking antiplatelet therapy. Terrence W. Norchi, MD, President and CEO of Arch Therapeutics, said, "We have eagerly awaited initial data to support the hypothesis that the mechanism of action of AC5 is independent of a patient's underlying bleeding or coagulation status. These results are an important first step in highlighting an important differentiating feature of AC5 and our self-assembling peptide technology platform." Jack Kelly, MD, Principal Investigator of the study, and a plastic, reconstructive and aesthetic surgeon and Professor of Surgery at Galway University Hospital, Galway, Ireland, said, "We have been impressed with how patients in this study responded to treatment and how easy AC5 was to use. The favorable safety and efficacy profile of AC5 in the overall study was supported when looking at the subset of patients taking antiplatelet therapy, which is particularly noteworthy. Many patients have perturbed hemostasis pathways, whether from natural disease or the use of prescribed or over the counter blood thinners, therefore we always have a concern about more bleeding in these patients. AC5 may provide their care providers a valuable tool to address those challenges." As previously reported, this first study assessing the safety and performance of AC5 in humans served to evaluate the safety and performance of AC5 in patients scheduled to undergo excision of skin lesions on their trunk or upper limbs. Of the 46 patients enrolled in the human study, 10 patients were taking an antiplatelet agent and 36 were not. Each patient had two wounds, of which one was treated with AC5 and the other received standard care plus a sham treatment according to a randomization process. Consequently, each patient served as her/his own control. The study's overall primary objective of safety throughout the surgical procedure and until the end of a 30-day follow-up period post procedure was met and AC5 was well tolerated. No serious adverse events were reported. A secondary endpoint was performance as assessed by time to hemostasis. The median time to hemostasis of wounds in the AC5 treatment group was 41% faster than for those in the control group. This result was statistically significant (p<0.001, Wilcoxon signed rank test). An additional secondary endpoint of healing of treated wounds was assessed as measured by the ASEPSIS wound score at Days 7 and 30. The majority of patients had an ASEPSIS score of 0 in both wounds on both days, and all AC5-treated wounds healed satisfactorily as per wound healing scoring criteria. Previously, Arch's clinical advisory committee deemed the study results to be clinically significant and have recommended submitting a manuscript to a peer-reviewed medical journal for publication. In light of this new data, the committee added, "This first human study assessing the safety and performance of AC5 has revealed an impressive and statistically significant result in patients on an antiplatelet agent, indicating that it may have broad potential scope in different applications." The advisors include Arthur Rosenthal, PhD, Professor of Practice, Emeritus, Department of Biomedical Engineering, Boston University, and a former member of Arch's Board of Directors; Steven Schwaitzberg, MD, Professor and Chairman of the Department of Surgery at the University of Buffalo's Jacobs School of Medicine and Biomedical Sciences and past President of the Society of American Gastrointestinal Endoscopic Surgeons; Paresh Shah, MD, Vice Chair of Surgery, Director of General Surgery and Professor of Surgery at New York University Langone Medical Center, New York University Langone School of Medicine; and William Denman, MD, anesthesiologist at Massachusetts General Hospital, past Chief Medical Officer of GE Healthcare and past Chief Medical Officer of Covidien. The Company expects to submit further study details and data to a peer-reviewed journal for publication. The Company also plans to include data from this trial in its regulatory filings, including in a CE mark application for AC5, which is currently anticipated to be filed at the earliest by the end of this year. Arch is currently planning its next clinical-regulatory steps for both the EU and the US. The study, conducted at University College Hospital, Galway, Ireland, was carried out in collaboration with CÚRAM, Science Foundation Ireland Centre for Research in Medical Devices and the HRB Clinical Research Facility based at National University of Ireland Galway. Arch Therapeutics, Inc. is a medical device company developing a novel approach to stop bleeding (hemostasis) and control leaking (sealant) during surgery and trauma care. Arch is developing products based on an innovative self-assembling peptide technology platform to make surgery and interventional care faster and safer for patients. Arch's flagship development stage product candidate, known as the AC5 Surgical Hemostatic Device™, is being designed to achieve hemostasis in surgical procedures. The HRB Clinical Research Facility, Galway (CRFG) is a joint venture between Galway University Hospitals (GUH), Saolta, and National University of Ireland, Galway (NUIG) and has been in operation since March 2008. The HRB-CRFG provides the infrastructure, physical space, facilities, expertise and culture needed to optimally support clinical research. It focuses on studies aimed at understanding a range of diseases and speedily translating the knowledge obtained through this research work into advances in patient care. CÚRAM is the Science Foundation Ireland Centre for Research in Medical Devices, based at NUI Galway. Supported by Science Foundation Ireland (SFI) and industry partners, CÚRAM enhances Ireland's standing as a major hub for the global medical devices industry. Its goal is to radically improve quality of life for patients with chronic illness by developing the next generation of smart, implantable medical devices. CÚRAM's innovative approach incorporates biomaterials, drug delivery, cell based technologies, glycosciences and device design to enhance, develop and validate both traditional and new combinational medical devices, from molecular design stage to implant manufacturing. CÚRAM's devices are being developed with strong clinical collaborations to enable rapid translation of research findings to clinical application. Key to the approach is the establishment of unique networks of national and international collaborations, integrating world class clinical, academic and industrial partners This news release contains "forward-looking statements" as that term is defined in Section 27(a) of the Securities Act of 1933, as amended, and Section 21(e) of the Securities Exchange Act of 1934, as amended. Statements in this press release that are not purely historical are forward-looking statements and include any statements regarding beliefs, plans, expectations or intentions regarding the future. Such forward-looking statements include, among other things, references to novel technologies and methods, our business and product development plans and projections, or market information. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies and operating as a development stage company, our ability to retain important members of our management team and attract other qualified personnel, our ability to raise the additional funding we will need to continue to pursue our business and product development plans, our ability to obtain required regulatory approvals, our ability to develop and commercialize products based on our technology platform, and market conditions. These forward-looking statements are made as of the date of this news release, and we assume no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements. Although we believe that any beliefs, plans, expectations and intentions contained in this press release are reasonable, there can be no assurance that any such beliefs, plans, expectations or intentions will prove to be accurate. Investors should consult all of the information set forth herein and should also refer to the risk factors disclosure outlined in the reports and other documents we file with the SEC, available at www.sec.gov. On Behalf of the Board, Terrence W. Norchi, MD Arch Therapeutics, Inc.
Kgosidialwa O.,Galway University Hospital |
Egan A.M.,Galway University Hospital |
Carmody L.,Galway University Hospital |
Kirwan B.,Galway University Hospital |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: Prevalence of gestational diabetes mellitus (GDM) and obesity continue to increase. Objective: This study aimed to ascertain whether diet and exercise is a successful intervention for womenwithGDMand whether a subset of these women have comparable outcomes to those with normal glucose tolerance (NGT). Design, Setting, and Participants: This was a retrospective cohort study of five antenatal centers along the Irish Atlantic seaboard of 567 women diagnosed with GDM and 2499 women with NGT during pregnancy. Intervention: Diet and exercise therapy on diagnosis of GDM were prescribed and multiple maternal and neonatal outcomes were examined. Results: Infants of women with GDM were more likely to be hypoglycemic (adjusted odds ratio [aOR], 7.25; 95% confidence interval [CI], 2.94-17.9) at birth. They were more likely to be admitted to the neonatal intensive care unit (aOR, 2.16; 95% CI, 1.60-2.91). Macrosomia and large-forgestational-age rates were lower in the GDM group (aOR, 0.48; 95% CI, 0.37-0.64 and aOR, 0.61; 95% CI, 0.46-0.82, respectively). There was no increase in small for gestational age among offspring of women with GDM (aOR, 0.81; 95% CI, 0.49-1.34). Women with diet-treated GDM and body mass index (BMI)<25 kg/m2 had similar outcomes to those with NGT of the same BMI group. Obesity increased risk for poor pregnancy outcomes regardless of diabetes status. Conclusion: Medical nutritional therapy and exercise for women with GDM may be successful in lowering rates of large for gestational age and macrosomia without increasing small-for-gestational-age rates.WomenwithGDMandaBMIless than 25kg/m2hadoutcomes similar to those with NGT suggesting that these women could potentially be treated in a less resource intensive setting. Copyright © 2015 by the Endocrine Society.
Zafar H.,National University of Ireland |
Sharif F.,University Hospital |
Sharif F.,HRB Clinical Research Facility |
Sharif F.,National University of Ireland |
And 2 more authors.
International Heart Journal | Year: 2014
Frequency domain optical coherence tomography (FD-OCT) provides cross-sectional images of coronary arteries and deployed stents with micron resolution and measures lumen dimensions with excellent reproducibility. FD-OCT combined with a blood flow resistances model can overcome many limitations of conventional measures of stenosis severity based on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The aim of this feasibility study was to investigate the relationship between pressure derived fractional flow reserve (FFR) and FD-OCT derived FFR, a new method for quantitative measure of stenosis severity that estimates the blood flow resistance and microvascular resistance of the vessel segments imaged by FD-OCT. A total of 26 coronary stenoses in 20 patients were studied consecutively with QCA, pressure derived FFR, and FD-OCT. There was a moderate but significant correlation between pressure derived FFR and FD-OCT derived FFR (r = 0.69, P < 0.001). Bland-Altman analysis showed that the mean differences between pressure derived FFR and FD-OCT derived FFR were 0.05 ± 0.14 (limits of agreement: -0.09 to 0.19). The root mean square error (RMSE) between FD-OCT derived FFR and pressure derived FFR was found to be ± 0.087 FFR units. FD-OCT derived FFR has the potential to become a valuable tool for the assessment of coronary artery stenosis.
Zafar H.,National University of Ireland |
Ullah I.,University Hospital Galway |
Dinneen K.,University Hospital Galway |
Matiullah S.,University Hospital Galway |
And 6 more authors.
Journal of Cardiology | Year: 2014
Objectives: The main objective of this study is to determine the correlation between fractional flow reserve (FFR)- and frequency domain optical coherence tomography (FD-OCT)-measured lumen parameters, and to determine the diagnostic competence of FD-OCT concerning the identification of severe coronary stenosis. Methods: A total of 41 coronary stenoses in 30 patients were assessed consecutively by quantitative coronary angiography (QCA), FFR, and FD-OCT. Stenoses were labeled severe if FFR. ≤. 0.80. The minimal lumen area (MLA), minimal lumen diameter (MLD), and percent lumen area stenosis (%AS) were measured using FD-OCT. Results: FFR was ≤0.80 in 10 stenoses (24.4%). A poor but significant correlation between FFR and FD-OCT-measured MLA (r2=0.4, p<0.001), MLD (r2=0.28, p<0.001), and %AS (r2=0.13, p=0.02) was found. In the overall group, the diagnostic efficiency of MLA and MLD in identifying significant stenosis was moderate. The area under the curve (AUC) was 0.80 [95% confidence interval (CI): 0.64-0.91] for MLA and 0.76 (95% CI: 0.60-0.88) for MLD. The best cut-off values of FD-OCT-measured lumen parameters to identify stenosis with FFR≤0.80 were 1.62mm2 [specificity 97%, sensitivity 70%, positive predictive value (PPV) 89% and negative predictive value (NPV) 91%] for MLA and 1.23mm (specificity 87%, sensitivity 70%, PPV 64% and NPV 90%) for MLD. The diagnostic efficiency of MLA in identifying significant stenosis in vessels having reference diameter<3mm was high. The AUC was 0.96 (95% CI: 0.83-1.0). Conclusions: The FFR values and FD-OCT anatomical parameters MLA, MLD were found to be significantly correlated. In the overall group, the FD-OCT-measured MLA and MLD have shown moderate diagnostic efficiency in the functional evaluation of significant stenosis. FD-OCT-measured MLA has high diagnostic efficiency in identifying severe coronary stenosis in vessels having reference diameter <3. mm. © 2013 Japanese College of Cardiology.
Monaghan D.,National University of Ireland |
O'Connell E.,National University of Ireland |
Cruickshank F.L.,University of Edinburgh |
O'Sullivan B.,National University of Ireland |
And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2014
Anisomycin was identified in a screen of clinical compounds as a drug that kills breast cancer cells (MDA16 cells, derived from the triple negative breast cancer cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells died by apoptosis. There was no correlation between cell death and either protein synthesis or JNK activation, which had previously been implicated in anisomycin-induced cell death. In addition, anisomycin analogues that did not inhibit protein synthesis or activate JNK retained the ability to induce cell death. These data suggest that either a ribosome-ANS complex is a death signal in the absence of JNK activation or ANS kills cells by binding to an as yet unidentified target. © 2013 Elsevier Inc. All rights reserved.
McElwain J.,Clinical science Institute |
Simpkin A.,HRB Clinical Research Facility |
Newell J.,National University of Ireland |
Laffey J.G.,Clinical science Institute
Anaesthesia | Year: 2011
The purpose of this study was to determine whether the Intubation Difficulty Scale is meaningful when used with indirect laryngoscopes. Data were analysed from previously published clinical trials from our group that compared the indirect laryngoscopes with the Macintosh laryngoscope. For each laryngoscope type, the Intubation Difficulty Scale score obtained for each tracheal intubation was correlated with data for duration of the intubation attempt and with the user rated difficulty of the intubation attempt. The strengths of the correlations between these indices were then compared for tracheas intubated with the Macintosh vs the indirect laryngoscopes. The Intubation Difficulty Scale performed well when compared with data for duration and user rated difficulty of the intubation attempts for the both direct and indirect laryngoscopy. However, the correlation between the Intubation Difficulty Scale score and both user rated difficulty (p = 0.001) and the duration of tracheal intubation (p = 0.003) were significantly stronger for the Macintosh laryngoscope compared with the indirect laryngoscopes. In contrast, the correlation between user rated difficulty scores and the data for duration of tracheal intubation was not different between the device types. The Intubation Difficulty Scale performs less well with indirect laryngoscopes than with the Macintosh laryngoscope. These findings suggest the need for caution with the use of this score with indirect laryngoscopes. You can respond to this article at © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.
PubMed | National University of Ireland, HRB Clinical Research Facility and University of Edinburgh
Type: Journal Article | Journal: Biochemical and biophysical research communications | Year: 2014
Anisomycin was identified in a screen of clinical compounds as a drug that kills breast cancer cells (MDA16 cells, derived from the triple negative breast cancer cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells died by apoptosis. There was no correlation between cell death and either protein synthesis or JNK activation, which had previously been implicated in anisomycin-induced cell death. In addition, anisomycin analogues that did not inhibit protein synthesis or activate JNK retained the ability to induce cell death. These data suggest that either a ribosome-ANS complex is a death signal in the absence of JNK activation or ANS kills cells by binding to an as yet unidentified target.
Simpkin A.,University of Bristol |
Newell J.,HRB Clinical Research Facility
Computational Statistics and Data Analysis | Year: 2013
P-Splines are commonly used for derivative estimation where a non-linear relationship exists between the response and explanatory variables. However, questions about the error of these estimates have arisen. Incorporating an extra penalty term in a P-Spline model is proposed as an improvement when derivative estimation is of primary concern. This additive penalty approach to derivative estimation is shown to improve on the P-Spline estimates based on the results of a simulation study to compare the performance when estimating the first and second derivatives of six simulated functions. A method for generating variability bands for P-Spline derivative estimates with and without an additive penalty is given. The proposed additive penalty variability bands are shown to behave better than their single penalty counterpart. Motivating examples in environmental and sports science are used to demonstrate the need for accurate derivative estimates and the benefit of using an additional penalty term to this end. © 2013 Elsevier B.V. All rights reserved.