News Article | May 5, 2017
JERUSALEM--(BUSINESS WIRE)--Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced that data suggests that women with relapsing forms of multiple sclerosis (RMS) who were exposed to COPAXONE® 20 mg/mL daily during pregnancy are not at higher risk for congenital anomalies compared to reference rates for abnormal pregnancy outcomes reported in two large databases representing the general population. These data appeared as an “Online First” article on the Website of the International Journal of MS Care (IJMSC) and represent the largest published analysis of pregnancy pharmacovigilance data for an RMS treatment. MS is more common among women of childbearing age compared with any other age group. The average age of diagnosis is 30, and many women go on to have children after diagnosis. Approximately half of pregnancies are unintended, which means that women with MS may become pregnant unexpectedly while taking an MS treatment. None of the MS therapies are approved for use during pregnancy. “Physicians now have this data to consider as they consult with their RMS patients planning a family or already pregnant, to make individual treatment decisions,” said Patricia K. Coyle, M.D., professor and vice chair (clinical affairs) of neurology, and the director of the Multiple Sclerosis Comprehensive Care Center at the Stony Brook University Medical Center, Stony Brook, New York. The analysis published in IJMSC compared 5,025 pregnancy cases with known outcomes from the Glatiramer Acetate (GA) Pharmacovigilance Database to two other databases of healthy women, the Metropolitan Atlanta Congenital Defects Program (MACDP)1 and the European Surveillance of Congenital Anomalies (EUROCAT)2. When compared to the rate of congenital anomalies from the MACDP database, the rate for prospective pregnancies among women exposed to COPAXONE® while pregnant from the GA Pharmacovigilance Database was comparable to the general U.S. population. Similarly, the comparison between the GA Pharmacovigilance and EUROCAT data indicated that the rate of congenital anomalies is very similar to that of the general European population. “With more than 20 years of data collected on COPAXONE®, we are able to share this important analysis with physicians to consider and counsel their patients of child-bearing age,” said Rob Koremans, M.D., President and CEO, Teva Global Specialty Medicines. “We are pleased to put forward this data that may help facilitate that conversation.” The publication, “Pregnancy Outcomes from the Branded Glatiramer Acetate Pregnancy Database,” is available online at http://ijmsc.org/doi/abs/10.7224/1537-2073.2016-079. The International Journal of MS Care is the official peer-reviewed publication of the Consortium of Multiple Sclerosis Centers (CMSC). COPAXONE® (glatiramer acetate injection) is indicated for the treatment of patients with relapsing forms of multiple sclerosis. The most common side effects of COPAXONE® are redness, pain, swelling, itching, or a lump at the site of injection, flushing, rash, shortness of breath, and chest pain. COPAXONE® is rated as Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Administration of glatiramer acetate by subcutaneous injection to pregnant rats and rabbits resulted in no adverse effects on offspring development. Animal reproduction studies are not always predictive of human response, therefore COPAXONE® should be used during pregnancy only if clearly needed. See additional important information at: www.CopaxonePrescribingInformation.com. For hardcopy releases, please see enclosed full prescribing information. The COPAXONE® brand is approved in more than 50 countries worldwide, including the United States, Russia, Canada, Mexico, Australia, Israel, and all European countries. Patients allergic to glatiramer acetate or mannitol should not take COPAXONE®. Some patients report a short-term reaction right after injecting COPAXONE®. This reaction can involve flushing (feeling of warmth and/or redness), chest tightness or pain with heart palpitations, anxiety, and trouble breathing. These symptoms generally appear within minutes of an injection, last about 15 minutes, and go away by themselves without further problems. During the postmarketing period, there have been reports of patients with similar symptoms who received emergency medical care. If symptoms become severe, patients should call the emergency phone number in their area. Patients should call their doctor right away if they develop hives, skin rash with irritation, dizziness, sweating, chest pain, trouble breathing, or severe pain at the injection site. If any of the above occurs, patients should not give themselves any more injections until their doctor tells them to begin again. Chest pain may occur either as part of the immediate postinjection reaction or on its own. This pain should only last a few minutes. Patients may experience more than one such episode, usually beginning at least one month after starting treatment. Patients should tell their doctor if they experience chest pain that lasts for a long time or feels very intense. A permanent indentation under the skin (lipoatrophy or, rarely, necrosis) at the injection site may occur, due to local destruction of fat tissue. Patients should follow proper injection technique and inform their doctor of any skin changes. The most common side effects of COPAXONE® are redness, pain, swelling, itching, or a lump at the site of injection, flushing, rash, shortness of breath, and chest pain. These are not all of the possible side effects of COPAXONE®. For a complete list, patients should ask their doctor or pharmacist. Patients should tell their doctor about any side effects they have while taking COPAXONE®. Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading global pharmaceutical company that delivers high-quality, patient-centric healthcare solutions used by approximately 200 million patients in 100 markets every day. Headquartered in Israel, Teva is the world’s largest generic medicines producer, leveraging its portfolio of more than 1,800 molecules to produce a wide range of generic products in nearly every therapeutic area. In specialty medicines, Teva has the world-leading innovative treatment for multiple sclerosis as well as late-stage development programs for other disorders of the central nervous system, including movement disorders, migraine, pain and neurodegenerative conditions, as well as a broad portfolio of respiratory products. Teva is leveraging its generics and specialty capabilities in order to seek new ways of addressing unmet patient needs by combining drug development with devices, services and technologies. Teva's net revenues in 2016 were $21.9 billion. For more information, visit www.tevapharm.com. This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding the potential benefits of COPAXONE® which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: and other factors discussed in our Annual Report on Form 20-F for the year ended December 31, 2016 (“Annual Report”), including in the section captioned “Risk Factors,” and in our other filings with the U.S. Securities and Exchange Commission, which are available at www.sec.gov and www.tevapharm.com. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. 1 Population-based tracking system for birth defects. The MACDP was established in 1967 by the Centers for Disease Control and Prevention (CDC), Emory University, and the Georgia Mental Health Institute. 2 European network of population-based registries for the epidemiologic surveillance of congenital anomalies
Mathison M.,Stony Brook University Medical Center
Journal of the American Heart Association | Year: 2012
In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.
Chandrakantan A.,Stony Brook University Medical Center |
Glass P.S.A.,Stony Brook University Medical Center
British Journal of Anaesthesia | Year: 2011
Summary. Postoperative nausea and vomiting (PONV) and pain are two of the major concerns for patients presenting for surgery. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, anaesthetic technique, and surgical procedure. Antiemetics work on several different receptor sites to prevent or treat PONV. This is probably why numerous studies have now demonstrated that using more than one antiemetic is usually more effective and results in fewer side-effects than simply increasing the dose of a single antiemetic. A multimodal approach to PONV should not be limited to drug therapy alone but should involve a holistic approach starting before operation and continuing intraoperatively with risk reduction strategies to which are added prophylactic antiemetics according to the assessed patient risk for PONV. With the increasing understanding of the pathophysiology of acute pain, especially the occurrence of peripheral and central hypersensitization, it is unlikely that a single drug or intervention is sufficiently broad in its action to be adequately effective, especially with moderate or greater pain. Although morphine and its congeners are usually the foundation of pain management regimens, as their dose increases so does the incidence of side-effects. Thus, the approach for the management of acute postoperative pain is to use multiple drugs or modalities (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects. © The Author . Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
Stergiopoulos K.,Stony Brook University Medical Center
Journal of the American College of Cardiology | Year: 2011
To varying extents, women with pre-existing cardiomyopathies have a limited cardiovascular reserve. The hemodynamic challenges of pregnancy, labor, and delivery pose unique risks to this group of patients, which can result in clinical decompensation with overt heart failure, arrhythmias, and rarely, maternal death. A multidisciplinary team approach and a controlled delivery are crucial to adequate management of patients with underlying heart disease. Pre-conception planning and risk assessment are essential, and proper counseling should be offered to expectant mothers with regard to both the risks that pregnancy poses and the implications for future offspring. In this article, we will review the hemodynamic stressors that pregnancy places upon women with pre-existing cardiomyopathies and risk assessment and discuss what evidence exists with regard to the management of 2 forms of cardiomyopathy during pregnancy, labor, and delivery: dilated and hypertrophic cardiomyopathy. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Iwashyna T.J.,University of Michigan |
Ely E.W.,Vanderbilt University |
Smith D.M.,Stony Brook University Medical Center |
Langa K.M.,University of Michigan
JAMA - Journal of the American Medical Association | Year: 2010
Context: Cognitive impairment and functional disability are major determinants of caregiving needs and societal health care costs. Although the incidence of severe sepsis is high and increasing, the magnitude of patients' long-term cognitive and functional limitations after sepsis is unknown. Objective: To determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their presepsis functioning. Design, Setting, and Patients: A prospective cohort involving 1194 patients with 1520 hospitalizations for severe sepsis drawn from the Health and Retirement Study, a nationally representative survey of US residents (1998-2006). A total of 9223 respondents had a baseline cognitive and functional assessment and had linked Medicare claims; 516 survived severe sepsis and 4517 survived a nonsepsis hospitalization to at least 1 follow-up survey and are included in the analysis. Main Outcome Measures: Personal interviews were conducted with respondents or proxies using validated surveys to assess the presence of cognitive impairment and to determine the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance. Results: Survivors' mean age at hospitalization was 76.9 years. The prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio (OR) of 3.34 (95% confidence interval [CI], 1.53-7.25) in multivariable regression. Likewise, a high rate of new functional limitations was seen following sepsis: in those with no limits before sepsis, a mean 1.57 new limitations (95% CI, 0.99-2.15); and for those with mild to moderate limitations before sepsis, a mean of 1.50 new limitations (95% CI, 0.87-2.12). In contrast, nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment (OR, 1.15; 95% CI, 0.80-1.67; P for difference vs sepsis=.01) and with the development of fewer new limitations (mean among those with no limits before hospitalization, 0.48; 95% CI, 0.39-0.57; P for difference vs sepsis <.001 and mean among those with mild to moderate limits, 0.43; 95% CI, 0.23-0.63; P for difference=.001). The declines in cognitive and physical function persisted for at least 8 years. Conclusions: Severe sepsis in this older population was independently associated with substantial and persistent new cognitive impairment and functional disability among survivors. The magnitude of these new deficits was large, likely resulting in a pivotal downturn in patients' ability to live independently. ©2010 American Medical Association. All rights reserved.
Stanat S.J.C.,Stony Brook University Medical Center |
Capozzi J.D.,Winthrop University
Journal of Arthroplasty | Year: 2012
Postoperative squeaking in ceramic-on-ceramic total hip arthroplasty is a recently emerging phenomenon. We performed a meta-analysis of published data to examine patient and procedural risk factors. Twelve studies (6137 patients, total) were analyzed, with 150 patients (2.4%) complaining of squeaking. The only significant patient risk factor was increasing body mass index (P =.03, n = 2957). There was no significance found with patient age, sex, height, weight, or procedural laterality for squeak incidence. For implant type, the presence of a Stryker Accolade femoral stem (beta-titanium; Stryker Orthopedics, Mahwah, NJ) was significantly found to increase squeak (P <.0001, n = 4654). The presence of a raised metallic lip on the acetabular component was not found to be associated with squeak. Acetabular cup position was also not found to have a significant bearing on the incidence of squeaking. © 2012 Elsevier Inc.
Coyle P.K.,Stony Brook University Medical Center
CNS Drugs | Year: 2013
There are currently nine approved disease modifying therapies for relapsing forms of multiple sclerosis, with six distinct mechanisms of action. All have side effects, and none are cures. When a patient cannot tolerate therapy, or there is unacceptable breakthrough disease activity, the most common approach is to change drug. No universal guidelines exist for switching therapy. This overview will propose switch principles and suggestions. © 2013 Springer International Publishing Switzerland.
Ranpura V.,Stony Brook University Medical Center |
Hapani S.,Stony Brook University Medical Center |
Wu S.,Stony Brook University Medical Center
JAMA - Journal of the American Medical Association | Year: 2011
Context: Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear. Objective: To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab. Data Sources: PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies. Study Selection and Data Extraction: Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Data Synthesis: A total of 10 217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P=.01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P=.045) but not with tumor types (P=.13) or bevacizumab doses (P=.16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%). Conclusion: In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality. ©2011 American Medical Association. All rights reserved.
Bronson R.,Stony Brook University Medical Center
American Journal of Reproductive Immunology | Year: 2011
Citation Bronson R. Biology of the male reproductive tract: Its cellular and morphological considerations. Am J Reprod Immunol 2011; 65: 212-219 For many years, the focus of attention in the study of semen has been on spermatozoa, its major cellular component, given their importance in the process of reproduction, and the role of the seminal fluid as their transport medium. More recently, evidence has accumulated of the complexity of seminal fluid, its components that perturb the female reproductive tract in ways promoting both survival of spermatozoa there-in and facilitating the implantation of embryos within the endometrium, hence initiating pregnancy. These same factors, however, may also make the female reproductive tract susceptible to invasion not only by spermatozoa but viruses, playing a significant role in the male-to-female transmission of HIV. Knowledge of the histology, anatomy, and immunology of the male reproductive tract is essential in understanding its role in HIV pathogenesis. © 2010 John Wiley & Sons A/S.
Richman D.C.,Stony Brook University Medical Center
Anesthesiology Clinics | Year: 2010
Ambulatory surgery currently represents more than two thirds of surgeries performed. It is considered low-risk surgery and patients expect to be discharged home safely and comfortably the same day. More than 30 years of evidence supports the idea that preoperative assessment is best done by a focused history and physical, and only minimal, selective, further laboratory investigations. Costs are optimized by this approach and outcomes have not been shown to be adversely affected, possibly even improved, with less harm inflicted by additional testing. This article focuses on what is appropriate testing for ambulatory surgery patients. © 2010 Elsevier Inc. All rights reserved.