Surgical Site Infection and Implications on the Orthopedic Implant Market

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Surgical Site Infection and Implications on the Orthopedic Implant Market

Research and Market Analysis

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Surgical site infection (SSI), one that occurs within 30 days of a surgical procedure or within one year of a foreign body implant, is considered a preventable source of significant morbidity, mortality, and economic cost.i In the US, overall SSIs account for 14-‐16% of all hospital-‐acquired infections, and it is estimated that, on patients developing SSIs, cost is increased by $3,152 per admission and hospital stay is lengthened by seven days per admission.ii Approximately 70% of SSIs are superficial infections, while the remaining are more invasive, involving deeper tissues, organs, and/or implanted material. Although the majority of SSIs do not develop into life-‐threatening infections, the tremendous numbers of surgical procedures performed annually make the incidence significant. In the US alone, there are about 27 million surgical procedures performed each year, with about 290,000 SSIs (slightly more than 1%) and approximately 8,000 deaths associated with these procedures.iii Within orthopedic surgery in the US, there are over 4 million orthopedic procedures performed each year, with a SSI rate typically less than 1%.1 In the US there are approximately 2 million fracture-‐fixation devices inserted annually and, on average, approximately 5% of initially inserted internal fixation devices become infected at an additional cost of about $15,000,iv while in the UK implant-‐associated infections are estimated to cost £7−11 million per year.v Internal fixation of closed fractures has a lower incidence of infection (1−2%), while the incidence may exceed 30% after internal fixation of open fractures.vi,vii,viii,ix Infection is believed to be responsible for causing failure in approximately 1% of hip implants, 4% of knee implants, and more than 15% of orthopedic trauma-‐related implants,x adding an estimated $3.8 billion to annual US healthcare costs.xi National efforts to decrease the incidence of postoperative infection are ongoing throughout the world, and are commonly referred to as Infection Control programs. In addition, the World Health Organization (WHO), while primarily focused on infection control policies to prevent and control spread of epidemic-‐ and pandemic-‐prone respiratory diseases' pathogens, also promotes its own guidelines on preventing and/or controlling healthcare-‐associated and ventilator-‐associated infections.xii In the US, the Centers for Disease Control (CDC), The Joint Commission (TJC), and others, have all developed guidelines for preventing healthcare-‐associated infections.xiii

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In terms of SSI, including orthopedic SSIs, the most important organism remains Staphylococcus aureus, most often brought into the hospital by the patient in their nares.xiv Other common causative organisms include methicillin-‐resistant Staphylococcus aureus (MRSA), vancomycin-‐resistant Enterococcus species, extended-‐spectrum ß-‐lactamase–producing Escherichia coli or Klebsiella species, and fluoroquinolone-‐ or carbapenem-‐resistant Enterobacteriaceae or Pseudomonas aeruginosa.xv,xvi Although the use of antimicrobial prophylaxis or preemptive therapy has decreased the frequency of implant-‐associated infections,xvii fighting implant infection remains a complex and lengthy process.xviii

Commonly identified microorganisms causing infections associated with fracture-‐fixation devices.

Microorganism Frequency (%)

Staphylococcus aureus 30

Coagulase-‐negative staphylococci 22

Gram-‐negative bacilli 10

Anaerobes 5

Enterococci 3

Streptococci 1

Polymicrobial 27

Unknown 2 From: Diagnosis and treatment of infections associated with fracture-‐fixation devices. A Trampuz, WZimmerli. Injury, Int. J. Care Injured. 37:S59—S66. 2006. It is estimated as many as 30% of surgical patients are active carriers of Staphylococcus aureus.xix Nasal carriage of Staphylococcus aureus has been shown to be the lone independent risk factor for surgical site infection following orthopedic implant procedures.xx Almost 50% of invasive SSIs in orthopedic procedures caused by Staphylococcus aureus, and half of these are caused by Methicillin-‐resistant Staphylococcus aureus (MRSA). MRSA is also a significant factor as it is more virulent than non-‐resistant Staphylococcus aureus, it more readily survives outside of a host,xxi and has a greater incidence of significant morbidity and mortality associated with it.xxii MRSA has recently shown continued shift from a hospital-‐associated to a community-‐acquired onset, although incidence of invasive MRSA in the US has recently been reported to be on the decline with an

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estimated 9.4% decrease in hospital-‐associated and an estimated 5.7% decrease in community-‐onset cases.xxiii Similar statistics have been reported in England and the rest of Europe, with a 24% decrease in Staphylococcus aureus bacteremia and a 17% decrease in the proportion of those cases involving MRSA in England.xxiv Despite these encouraging decreases in infection, it is unclear whether these decreases can be attributed to traditional hospital infection prevention and control measures or are due to normal changes in as many of the decreases began before the measures were widely instituted.24,xxv In the US, the Surgical Care Improvement Program (SCIP) was launched in July 2006, as a national quality partnership of organizations to improve surgical care by significantly reducing surgical complications such as SSIs. Several mechanisms were initiated to help prevent surgically related infections, including appropriate choice, timing, and duration of pre-‐, intra-‐ and/or post-‐operative antibiotics, clipping of hair around surgical incision site (instead of shaving), good blood glucose control in diabetics and keeping patients at a normal body temperature as much as possible.xxvi Similar national programs have been initiated worldwide. Classification of infections associated with fracture fixation devices.

CLASSIFICATION CHARACTERISTIC According to route of infection

• Perioperative Inoculation of microorganisms into surgical wound during surgery or immediately thereafter

• Contiguous Wound Contamination due to penetrating trauma (open fractures) or from an adjacent focus of infection (skin and soft-‐tissue lesions)

• Hematogenous Microbial spread through blood or lymph from distant focus of infection (eg, skin, lung, urinary tract)

According to onset of symptoms after implantation

Early infection (< 2 weeks)

Predominantly acquired during trauma or implant surgery; caused by highly virulent organisms (e.g., S. aureus, Gram-‐negative bacilli)

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Delayed infection (2−10 wks) Late infection (>10 wks)

Predominantly acquired during trauma or implant surgery; caused by low virulence organisms (e.g., coagulase-‐negative staphylococci); occasionally caused by hematogenous seeding from remote infections

From: Diagnosis and treatment of infections associated with fracture-‐fixation devices. A Trampuz, W Zimmerli. Injury, Int. J. Care Injured. 37:S59—S66. 2006. Risk factors for SSIs of all types are diabetes, obesity, older age, emergency status of operation, and obvious contamination of the injury or the surgical site.xxvii In orthopedic surgery, risk factors for SSI also include trauma and open fractures (preoperative), subsequent fracture-‐fixation procedures (intraoperative), or abnormalities in wound healing (postoperative).xxviii Hematogenous infection, primarily caused by blood stream infection (BSI) originating from skin, respiratory, oral, or urinary tract infection, is less common than SSI. Implant-‐associated infections are primarily caused by the previously-‐described bacteria growing in biofilm communities. These microorganisms live in a tightly clustered, highly-‐hydrated polysaccharide extracellular matrix (secreted by the microbes) adhered to a surface.xxixxxxxxxi Depletion of metabolic substances and/or accumulation of waste products within these biofilms causes the microbes to enter into a slow-‐growing or stationary phase enabling the bacteria to be as much as 10,000 times more resistant to antibiotics than “planktonic” bacteria. 18,xxxiixxxiii This surface adherence, for example on an orthopedic implant, occurs rapidly by either specific mechanisms such as adhesins (cell-‐surface components or appendages that facilitate adhesion or adherence of microbes), or by nonspecific mechanisms such as surface tension, hydrophobicity, and electrostatic forces).xxxiv Adherence to an implant surface is followed by an accumulative phase in which microbial cells adhere to one another and form a biofilm. The presence of a foreign body has been shown to significantly increase susceptibility to infection, with up to a 100,000 fold lower minimal infecting dose of Staphylococcus aureus causing an abscess in guinea pigs adjacent to subcutaneous devices due at least in part to a locally acquired granulocyte defect.xxxvxxxvi Current protocols for resolution of an implant infection most often require the implant be removed, the soft tissue surrounding the implant be cured of infection, and, once that is accomplished, a second prosthetic device implanted. This process often takes months and multiple tens of thousands of dollars.18

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A solution to this problem has been sought for many decades, and it is obvious that any solution will require a diverse array of expertise from many different disciplines. Attempts to decrease implant infection rates have included those listed in the table below.

Type of Modification Modification

Implant Surface

Modification

Mechanical Electropolishing of titanium surfaces

Protein-‐Resistant Coating

Titanium-‐nitride coatings

Heparin Coatings

Albumin coatings

Hydrophilic chain coating

Phosphorylcholine-‐modified polymer coatings

PEG-‐based coatings

Poly(l-‐lysine)-‐grafted-‐PEG coatings

Hyaluronic acid coatings

Antimicrobial Action

Antimicrobial Coating

Gentamicin-‐, Ciprofloxacin-‐, or Vancomycin -‐loaded biocompatible biodegradable polymer (e.g. PLGA or PDLLA)

Gentamicin-‐coated polyurethane sleeves

Antimicrobial Gels and Films

Antiseptic Coating

Chlorhexidine

Covalently bound Quaternary Ammonium compounds

Silver ion-‐ and silver nitrate-‐based coatings

Antibacterial Enzyme Lysostaphin

Antimicrobial Current

100 muA current through the stainless steel pins of a fixation device.

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At the present time, there remains an unmet need for a surface modification or coating that provides complete prevention of bacterial adhesion with no toxicity to adjacent tissue. Many of the methods listed above have significantly decreased the number and/or adherence of pathogenic bacteria; however, more studies are still needed. Ideally, the best solution for a surface would be a coating or treatment that would be biocompatible, allow fibroblast and osteoblast cells to adhere and proliferate leading to integration and vascularization in both hard and soft tissue, and prevent bacterial adherence. Additional potential solutions that have been studied include inkjet printing of nanocomposite micropatterns of calcium phosphate and antibiotic nanocrystals (~100 nm) dispersed in a biodegradable polymer matrix;18 Gentamicin-‐eluting bioresorbable composite fibers;xxxvii Nanoscale Particle Therapies;xxxviii Antibiotic Eluting Polypeptide; PLL/PLGA Nanocoatings;xxxix and Chitosan Films.xl That ideal solution, however, so far remains elusive. Overall, the global anti-‐invectives market is forecast to expand at an annual rate of 5.7% through 2013, with growth driven primarily by the anti-‐bacterial and anti-‐viral classes, while the orthopedic implant market is currently valued at more than $16 billion with a projected value exceeding $23 billion by 2012. The worldwide market for combination drug-‐device products is expected to be the highest growth segment of the medical products industry.xli

REFERENCES

i Surgical Site Infection. Frequently Asked Questions. CDC. December 17, 2008. http://www.cdc.gov/ncidod/dhqp/FAQ_SSI.html#

ii Infections. Surgical Care Improvement Project. http://www.qualitynet.org iii CDC 2001. iv Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med 350(14):1422−1429. [thesis].Ther Umsch; 47(7):593−596. 2004.

v Staphylococci and implant surfaces: a review. LG Harris, RG Richards. Injury. 37(2S):S3-‐S14. May 2006.

vi McGraw JM, Lim EV. Treatment of open tibial-‐shaft fractures. External fixation and secondary intramedullary nailing. J Bone Joint Surg Am; 70(6):900−911. 1998.

vii ObremskeyWT, Bhandari M, Dirschl DR, et al. Internal fixation versus arthroplasty of comminuted fractures of the distal humerus. J Orthop Trauma; 17(6):463−465. 2003.

viii Perren SM. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. J Bone Joint Surg Br; 84(8):1093−1110. 2002.

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ix Raahave D. Postoperative wound infection after implant and removal of osteosynthetic material. Acta Orthop Scand; 47(1):28−35. 1976.

x Fighting Bacterial Infection in Orthopedic Implants. Stevens Institute of Technology. Article. 12 December 2009.

xi Site Specific Delivery -‐ Global Impact. TYRX. 2010. http://www.tyrx.com/aboutus-‐company.htm

xii Infection prevention and control in health care. WHO. http://www.who.int/csr/bioriskreduction/infection_control/en/

xiii Management of Multidrug -‐Resistant Organisms In Healthcare Settings. JD Siegel, E Rhinehart, M Jackson, L Chiarello. The Healthcare Infection Control Practices Advisory Committee. CDC. 2006.

xiv Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 10:505-‐520. 1997.

xv Antimicrobial-‐Resistant Pathogens Associated With Healthcare-‐Associated Infections: Annual SummaryData Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007.

xvi AI Hidron, JR Edwards, J Patel, TC Horan, DM Sievert, DA Pollock, SK Fridkin. Infection Control and Hospital Epidemiology. 29(11):996-‐1011. Nov 2008.

xvii Zimmerli W. Antibiotic prophylaxis. Ruedi RP, Murphy WM. (Eds). AO Principles of fracture management. Stuttgart, Germany Thieme Verlag. 2006.

xviii NSF Funds Infection-‐Resistant Orthopedic Research. Stevens Institute of Technology. Press Release. 21 Jul 2010.

xix Gorwitz RJ, Kruszon-‐Moran D, McAllister SK, et al. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001-‐2004. J Infect Dis. 2008;197(9):1226-‐1234.

xx Kalmeijer MD, van Nieuwland-‐Bollen E, Bogaers-‐ Hofman D, de Baere GA. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-‐ site infections in orthopedic surgery. Infect Control Hosp Epidemiol. 21: 319-‐323. 2000.

xxi Sexton T, Clarke P, O’Neill E, Dillane T, Humphreys H. Environmental reservoirs of methicillin-‐resistant Staphylococcus aureus in isolation rooms: correlation with patient isolates and implications for hospital hygiene. J Hosp Infect. 62:187-‐94. 2006.

xxii Melzer M, Eykyn SJ, Gransden WR, Chinn S. Is methicillin-‐resistant Staphylococcus aureus more virulent than methicillin-‐susceptible S. aureus? A comparative cohort study of British patients with nosocomial infection and bacteremia. Clin Infect Dis. 37:1453-‐60. 2003.

xxiii Kallen AJ, Mu Y, Bulens S, et al. Health care–associated invasive MRSA infections, 2005-‐2008. JAMA. 304(6):641-‐648. 2010.

xxiv Wilson J, Elgohari S, Livermore DM, et al. Trends among pathogens reported as causing bacteraemia in England, 2004 to 2008 [published online ahead of print on May 18, 2010]. Clin Microbiol Infect. European Antimicrobial Resistance Surveillance System (EARSS) Annual Report 2008. Vol 2010. Bilthoven, the Netherlands: EARSS; 2008. http://www.rivm.nl/earss/Images/EARSS%202008_final_tcm61-‐65020.pdf.

xxv Climo MW. Decreasing MRSA infections: an end met by unclear means. JAMA. 301(7):772-‐773. 2009.

xxvi Surgical Care Improvement Project. QualityNet. http://www.qualitynet.org

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xxvii Postoperative Infections. JAMA Patient Page. JAMA. 303(24):2544. June 23/30, 2010.

xxviii Diagnosis and treatment of infections associated with fracture-‐fixation devices. A Trampuz,WZimmerli. Injury, Int. J. Care Injured. 37:S59—S66. 2006.

xxix Inhibiting Microbial Biofilm Formation by Brominated Furanones. S. Hou, M. Duo, Y. Han, Y. Y. Luk, D. Ren. J Bone Joint Surg. 2003.

xxx Trampuz A, Osmon DR, Hanssen AD, et al (2003) Molecular and antibiofilm approaches to prosthetic joint infection. Clin Orthop; 414:69−88.

xxxi S Hou, M Duo, Y Han Y-‐Y Luk, D Ren. Materials and Processes for Medical Devices. August 2009.

xxxii Donlan RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis; 8(9):881−890. 2002.

xxxiii Stewart PS Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet. 358(9276):135−138. 26. 2001.

xxxiv Darouiche RO (2001) Device-‐associated infections: a macroproblem that starts with microadherence. Clin Infect Dis. 33(9):1567−1572.

xxxv Zimmerli W, Waldvogel FA, Vaudaux P, et al (1982) Pathogenesis of foreign body infection: description and characteristics of an animal model. J Infect Dis. 146(4):487−497. 1982.

xxxvi Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreign body infection: Evidence for a local granulocyte defect. J Clin Invest. 73(4):1191−1200. 1984.

xxxvii Gentamicin-‐eluting bioresorbable composite fibers. For wound healing applications. Zilberman M, Golerkansky E, Elsner JJ, Berdicevsky I. J Biomed Mater Res A. 2009 Jun;89(3):654-‐66.

xxxviii Nanoscale Particle Therapies for Wounds and Ulcers. Roberta Cortivo; Vincenzo Vindigni; Laura Iacobellis; Giovanni Abatangelo; Paolo Pinton; Barbara Zavan. Nanomedicine. August 2, 2010.

xxxix Antibiotic Eluting Polypeptide PLL/PLGA Nanocoatings for the Potential Prevention of Biomedical Device-‐Associated Infections. Heather Ogle. West Virginia University. May 11, 2008.

xl Chitosan Films. A Potential Local Drug Delivery System for Antibiotics. Scott P. Noel MS, Harry Courtney PhD, Joel D. Bumgardner PhD, Warren O. Haggard PhD Clin Orthop Relat Res (2008) 466:1377–1382

xli Site Specific Delivery -‐ Global Impact. TYRX. 2010.

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Table 2: Examples of Potential Key Innovation Leaders

Person's Name Title/Expertise

Albert Lauritano, MSc, CLP Director, Business Development, Becton Dickinson

Dennis Crowley Vice President, Corporate Development, Covidien

Ted Davis Vice President, Business Development, Wright Medical

John Mack Senior Director, Business Development and Strategy, Medtronic CardioVascular

Matt Diohep Director of Marketing, OEM Products, Covidien

Chandan K. Sen, PhD

Department of Surgery & Molecular & Cellular Biochemistry; focuses on reactive oxygen species & anti-‐oxidant nutrients with emphasis on tissue injury and repair; Executive Director of OSU Comprehensive Wound Center

Gary Darnell Regional Business Director, Novo Nordisk

Lisa Gould, MD Chief, Plastic Surgery; Professor of Medicine at Univ. of South Florida; Secretary of the Wound Healing Society

Andrew Purcell Vice President of US Sales and Marketing, BD Diabetes Care; Previously served as VP of Strategic Business Development, Novo Nordisk

Michael Barszcz Director of Customer Segment Marketing, Novo Nordisk

Manas Kanungo Innovation Marketing Director, Global Strategic Marketing, WW Hospital and Emerging Markets, Abbott Diabetes Care

Charles Grubsztajn Vice President, Business Development, MethylGene

Nicole Gibran, MD

Research emphasizes aberrant healing process including hypertrophic scar formation and chronic non-‐healing wounds seen with diabetes; has over 100 publications in wound repair, response to injury and burns; Director of the UW Burn Center

Paul Fuller Executive Vice President, Stat Medical Devices, Inc.

Diane Lever Director, Business Development & Licensing, DSM Biologics

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Peter Hill, MD

At Johns Hopkins University -‐ Assistant Chief of Service; co-‐founder and Medical Director, Emergency-‐Acute Care Unit; Physician leader, Department of Emergency Medicine's 'Mid-‐Level Provider Group,' consisting of Nurse Practitioners and Physician Assistants who work in all three of the department's clinical venues; Clinical Director since 2005

Heather Steinman, PhD, MBA Senior Associate Director, Life Sciences Licensing, University of Pennsylvania

Pamela A. Lipsett, MD, FCCM

Professor of Surgery, Anesthesia, and Critical Care, and Nursing, and Co-‐Director, Surgical Intensive Care Units, Johns Hopkins University Schools of Medicine and Nursing; Program Director for General Surgery & Surgical Critical Care Fellowship

Robert Kirsner, MD, PhD

Director Univ. of Miami Hospital Wound Center; Chief, Dermatology Dep’t, Univ. of Miami Hospital; Co-‐directs Symposium for Advanced Wound Care; serves on planning committee for several meetings; editorial boards for dermatology and wound care journals; board member of Wound Healing Society; past president Association for the Advancement of Wound Care; chairs Medical Advisory Board for National Healing Corp

Mitchell M. Levy MD FCCM

Professor of Medicine, Warren Alpert Medical School, Brown University; Medical Director, Medical Intensive Care Unit at Rhode Island Hospital; Director of Critical Care Services, Rhode Island Hospital & Miriam Hospital, Providence, Rhode Island

Kristen Belmonte Director, Business Development & Licensing, Stiefel, a GSK Company Adjunct Assistant Professor, Johns Hopkins University

Sam Stupp, Ph.D. Board of Trustees Professor of Materials Science, Chemistry, and Medicine; Director, Institute for BioNanotechnology in Medicine

David Lewin Associate Director, Yale University Office of Cooperative Research

Ryan Bradley Global Licensing Director -‐ Global Marketing & Commercial Development, Amgen

Shuming Nie, Ph.D. The Wallace H. Coulter Distinguished Faculty Chair in Biomedical Engineering & Professor, Director for Emory-‐Georgia Tech Cancer Nanotechnology Center

Stephen Hemsley President and Chief Executive Officer of United Health Group. Prior to 2006, Chief Operating Officer at United Health Group.

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Wendy R. Sanhai, PhD

Senior Scientific Advisor, Immediate Office of the Commissioner, FDA, Nanotechnology Sub-‐Committee of the Interagency Oncology Task Force (IOTF) between FDA and NCI.

William S. Dynan, Ph.D. Professor and GRA Eminent Scholar, Chief, Nanomedicine and Gene Regulation Program, Institute of Molecular Medicine and Genetics

Tom Fenwick Strategic Sourcing Manager -‐ Chemicals & Biologicals, BD

Kathleen Greene Director, BDSI Strategic Sourcing, Process Improvement, & Records Information Management, Genzyme

Scott E. McNeil, PhD

Director, Nanotechnology Characterization Laboratory for the National Cancer Institute, Frederick; coordinates pre-‐clinical characterization of nanomaterials intended for cancer therapeutics & diagnostics; advisor to Industry, State & US Governments on development of nanotechnology; member of several governmental and industrial working groups related to nanotechnology policy; standardization and commercialization.

Alice Ting, Ph.D. Associate Professor, Department of Chemistry. Development of molecular probes for the study of cellular biochemistry

Bill Crow HTC Entrepreneur in Residence for NanoEnergy & NanoHealth

JP Scott, MD

Practicing physician and Professor of Medicine, Mayo Clinic. Interests include Cystic Fibrosis, Pulmonary Hypertension, Lung Transplantation Immunology, Pulmonary Connective Tissue Diseases, Medical Ethics.

John Buckley, MD, FCCP

Chair, Bylaws Committee and President, Association of Pulmonary and Critical Care Medicine Program Directors; Vice Chair for Quality -‐ Department of Internal Medicine, Indiana University School of Medicine.

Jeffrey Korsmo Executive Director, Mayo Clinic Health Policy Center

Chiming Wei, M.D., Ph.D.,

Director, Cardiothoracic-‐Renal Nanomedicine Program, Chairman of AANM, Editor-‐in-‐Chief, NANOMEDICINE, Editor-‐in-‐Chief, Journal of Cardiothoracic-‐Renal Research (JCRR)

Jeffery Schloss, Ph.D. Technology Development, Division of Extramural Research, National Human Genome Research Institute

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Christina Catlett, MD

Associate Director for Health System Preparedness, The Johns Hopkins Office of Critical Event Preparedness & Response (CEPAR); Assistant Professor, Department of Emergency Medicine.

Jeffrey Houpt, MD

Chairman of the Board, Blue Cross Blue Shield of North Carolina; Immediate past CEO of UNC Health Care System and Dean of the School of Medicine, University of North Carolina at Chapel Hill.

Jeroen de Wilt Regulatory Affairs Coordinator European Procedures, Merck Sharp & Dohme

Kevin Carroll Director, Data Operations and Global Standards, Bristol-‐Myers Squibb

Susan Deitch AD Policies and Procedures, Wyeth

Mary Kane Director, Financial Compliance & Procedures, Johnson & Johnson

Louis-‐André Villeneuve International Business Unit Leader, Roche Pharmaceuticals

Jos Verest Director of Strategic Operations, Novo Nordisk

David Harrison Regional Business Director, Boehringer Ingelheim

Surgical Site Infection and Implications on the Orthopedic Implant Market

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