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Saint-Maur-des-Fossés, France

Chitre M.,Clinical Services | Shechter D.,Scientific Affairs | Grauer A.,Amgen Inc.
American Journal of Health-System Pharmacy

Purpose. The pharmacologic properties, clinical efficacy, and safety profile of the injectable agent denosumab for the treatment of postmenopausal women with osteoporosis are reviewed. Summary. Denosumab, a human monoclonal antibody that targets a key protein mediator of bone resorption, was approved by the Food and Drug Administration in June 2010 for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, including "patients who have failed or are intolerant to other available osteoporosis therapy." Available in a 60-mg prefilled syringe, denosumab should be administered subcutaneously by a health care professional at six-month intervals. In Phase III clinical efficacy trials involving nearly 10,000 postmenopausal women, the use of denosumab was associated with a number of significant benefits: reduced bone resorption, increased bone mass, and reduced rates of vertebral, nonvertebral, and hip fractures. Results of two comparison studies indicated that denosumab therapy increased bone mineral density (BMD) at various skeletal sites to a significantly greater extent than alendronate therapy. In the largest clinical trial of the drug to date, adverse effects occurring significantly more often with denosumab versus placebo included eczema-related effects and cellulitis; long-term safety evaluations are ongoing. Conclusion. Denosumab has been shown to decrease bone resorption; increase BMD at all skeletal sites measured; and significantly reduce rates of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. Denosumab appears to have a favorable risk:benefit profile and provides a new treatment option for many patients in this population. Copyright © 2011, American Society of Health-System Pharmacists, Inc. All rights reserved. Source

Atkinson S.F.,University of North Texas | Sarkar S.,University of Texas at Austin | Avina A.,University of North Texas | Schuermann J.A.,Infectious Disease Control Unit | Williamson P.,Scientific Affairs
Geospatial Health

The spatial distribution of Ixodes scapularis, the most common tick vector of the bacterium Borrelia burgdorferi, the cause of Lyme disease in humans, has not been studied previously in Texas, United States of America. It has only rarely been reported in this state, so its local, spatial relationship to the distribution of this disease is unknown. From an epidemiological perspective, one would tend to hypothesise that there should be a high degree of spatial concordance between habitat suitability for the tick and incidence of the disease. Both maximum-entropy modelling of the tick’s habitat probability and modelling of human incidence of Lyme disease using spatially adaptive filters provide reliable portrayals of the spatial distributions of these phenomena. Even though rates of human cases of Lyme disease as well as rates of Ixodes ticks infected with Borrelia bacteria are both relatively low in Texas, the best data currently available indicate that the assumption of high levels of spatial concordance would not be correct in Texas (Kappa coefficient of agreement = 0.039). It will take substantially more data to provide conclusive findings and to understand the results reported here, but this study provides an approach to begin understanding the discrepancy. © 2014 University of Naples Federico II. All rights reserved. Source

Piercefield E.,Epidemic Intelligence Service Officer | Archer P.,Injury Prevention Service | Kemp P.,Analytical Research Laboratories | Mallonee S.,Scientific Affairs
American Journal of Preventive Medicine

Background During 19992006, rates of unintentional drug-related deaths increased 120% in the U.S. Purpose This report describes demographics and trends of unintentional medication overdose deaths among Oklahoma residents to target prevention strategies. Methods Oklahoma medical examiner data regarding fatal unintentional poisonings involving at least one prescription or over-the-counter medication during 19942006 and opioid retail sales data during 19972006 were analyzed during 20082009 to determine demographic-specific rates of overdose deaths and changes in 3-year mean death rates. Results A total of 2112 fatal unintentional medication overdoses were identified (4.7 deaths/100,000 population) involving a median of two substances/decedent. The highest fatality rates occurred among men (5.9/100,000) and people aged 3554 years (11/100,000). Crude overdose death rates increased sevenfold during the investigation period, peaking at 11/100,000 in 2006. Death rates increased more for women (ninefold) than men (sixfold); rates among residents of rural counties increased more (eightfold) than urban county rates (sixfold). Leading drug types involved in fatalities were opioids and anxiolytics. The individual drugs contributing most frequently included methadone (31%); hydrocodone (19%); alprazolam (15%); and oxycodone (15%). During 19972006, Oklahoma prescription opioid sales increased fourfold. Methadone was associated with the highest number of deaths per equianalgesic dose sold (23.3), whereas hydrocodone and oxycodone had the highest increases in deaths per equianalgesic dose sold (threefold increase each). Conclusions Unintentional medication-related deaths are increasing in Oklahoma and often involve multiple substances. Substances most frequently contributing to deaths were prescription opioid analgesics. Prevention strategies should target people aged 3554 years and emphasize the dangers of coingesting substances and misusing prescription pain medications. © 2010 American Journal of Preventive Medicine. Source

Manjelievskaia J.,Epidemiology | Erck D.,External Affairs | Piracha S.,External Affairs | Schrager L.,Scientific Affairs
Transactions of the Royal Society of Tropical Medicine and Hygiene

TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9-25 times higher than treating drug-susceptible TB. Developing newdrugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be 'resistant' to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035. © The Author 2016. Source

Patel P.,McMaster University | West-Mays J.,McMaster University | Kolb M.,McMaster University | Rodrigues J.-C.,University of Manitoba | And 2 more authors.
Matrix Biology

Platelet derived growth factor (PDGF) is involved in wound healing in various organ systems. Its potential role in the context of peritoneal injury following long-term peritoneal dialysis is unclear. We used an adenovirus expressing the B chain of PDGF (AdPDGF-B) to assess its effect on pro-fibrotic pathways in the peritoneal membrane. To assess the transforming growth factor (TGF) β independent effects of PDGF, we over-expressed PDGF-B in the peritoneum of either wild-type mice (Smad3+/+) or those with a deletion of the TGFβ signaling protein Smad3 (Smad3-/-). PDGF-B induced sustained angiogenesis in both Smad3+/+ and Smad3-/- mice. Despite increased collagen gene expression, collagen accumulation was transient and fibrogenesis was associated with induction of collagenase activity. We observed epithelial to mesenchymal transition (EMT) involving the peritoneal mesothelial cells, as shown by increased SNAIL and decreased E-Cadherin expression with evidence of mesothelial cells expressing both epithelial and mesenchymal markers. Unlike TGFβ-induced EMT, PDGF-B exposure did not lead to mobilization of the mesothelial cells; they remained as a single monolayer throughout the observation period. This "non-invasive" EMT phenomenon is a novel finding and may have implications concerning the role of EMT in peritoneal fibrosis and injury to other organ systems. The observed effects were similar in Smad3-/- and Smad3+/+ animals, suggesting that the PDGF-B effects were independent of TGFβ or Smad signaling. © 2009 International Society of Matrix Biology. Source

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