Reportlinker.com announces that a new market research report related to the Medical devices industry is available in its catalogue.

In Vitro Diagnostics Market Report and Analysis 2008-2023

http://www.reportlinker.com/p091991/In-Vitro-Diagnostics-Market-Report-and-Analysis-2008-2023.html

This brand new report examines the commercial prospects for in vitro diagnostics (IVD) in the global healthcare market. Technological solutions are playing an increasingly important role in both clinical practice and pharmaceutical R&D – increasing safety, speeding up clinical development and facilitating regulatory acceptance. Furthermore, current developments in diagnostics – especially molecular diagnostics – are paving the way towards the long-held goal of personalised medicine, to the benefit of patients, companies and healthcare providers. Developments in IVD also receive encouraging support from regulators such as the FDA. Visiongain believes that some of the greatest opportunities ever available for diagnostics companies are now there to be seized, with important sales, licensing and partnership developments from the present onwards.

Importantly, this report also covers theranostics, a fusion of drug therapy and diagnostics to optimise efficacy and safety, as well as streamlining drug development. Combining a drug with a diagnostic process or test is also known as companion diagnostics, integrated medicine, pharmacodiagnostics and Dx/Rx partnering. This emerging field is generating strong interest from the healthcare industry and regulatory bodies, with the associated market expanding as the importance of theranostics is recognised, especially in cancer.

Our new In Vitro Diagnostics Market Report & Analysis 2008-2023 report examines the market for in vitro diagnostic solutions critically, through comprehensive primary and secondary research. Importantly, visiongain discusses IVD in the context of the wider healthcare market, with a strong emphasis on theranostics and related molecular diagnostics/medicine. In addition to consultation with experts in industry – including full interview transcripts – this research involved a detailed study of relevant documents, industrial reports and current developments. Vitally, visiongain applied unique in-house forecasting techniques and analysis of drivers and restraints. The result is a totally independent in-depth market-based report with detailed analyses and informed opinion.

In particular, this report concentrates on the following essential aspects of the in vitro diagnostics sector:

– Technologies that drive the IVD sector, including those related to theranostics

– Key industrial players in IVD – both established and emerging – including partnerships

– Forecasts of the global IVD market from 2008-2023 – including those of principal market segments, both by disease area and technology

– Forecasts for IVD sales in leading national markets, including China and India

– Forecasts for theranostic applications – including therapeutic areas – from 2008-2023

– Drivers and opportunities in the IVD sector

– Restraints and threats in the IVD sector

– Assessments of relevant business models, technological solutions and associated issues

– Coverage of future trends in IVD and theranostics

– Insight from a comprehensive survey with relevant experts

Why you should buy this report:

– To receive a comprehensive analysis of the prospects for IVD from 2008-2023, including sales by disease area, technology and country

– To discover predicted revenues, growth rates and other key metrics for theranostic solutions from 2008-2023

– To receive the views of experts in the IVD sector regarding current and future trends

To determine the forces that influence the market for IVD:

– Competition

– Drivers

– Restraints

– Strengths, weaknesses, opportunities and threats

– To find out where the IVD market is heading – both technologically and commercially

Visiongain predicts that the markets for IVD and theranostics will exhibit strong growth in revenues from 2008-2023, with significant investments being made by far-sighted companies and healthcare providers. Although still in its early stages of commercial development, molecular diagnostics will increasingly gain acceptance from stakeholders in healthcare. You should be benefiting from this opportunity. You and your company can benefit as a result, gaining early market prominence from high-value products. You cannot afford to ignore current developments in diagnostics, especially as personalised medicine becomes an inevitable reality.

Please Note: Reports are sold based on the user licenses indicated. The Publisher delivers the report in Flash format via the publisher website, allowing viewing and printing capabilities only. Within one to two business days after placing the order, the Publisher will email the client with information on accessing their purchase. Prior to initiating fulfillment of an order, the client will be required to sign a document detailing the purchase terms for a publication from this publisher.

 1 Executive Summary: In Vitro Diagnostics Market 2008-2023  2 Introduction to In-Vitro Diagnostics  2.1 The Continuing Success of the Healthcare Industries is Dependent upon Important Drivers and Restraints  2.1.1 Drivers of Sales in Global Healthcare Markets from 2008-2023  2.1.2 The Global Healthcare Markets Will Also Face Considerable Restraints Throughout the Foreseeable Future  2.2 What are In Vitro Diagnostic (IVD) Tests?  2.2.1 In Vitro Diagnostics are Medical Assays  2.2.2 Diagnosis and Disease Management  2.2.3 Screening of Populations and Risk Factors  2.2.4 How are In Vitro Diagnostic Technologies Regulated by the FDA?  2.2.5 Point-of-Care Testing  2.3 Advanced Diagnostics and Personalised Medicine  2.3.1 Polymerase Chain Reaction (PCR)  2.3.2 Need for Better Targeted Medicine to Suit Patient Sub-Populations  2.3.3 The Dawn of Pharmacogenomic Medicine  2.3.4 Completion of the Human Genome Project Has Been a Major Driver of Molecular Diagnostics and Personalised Medicine  2.3.5 Personalised Medicine Will Rely Heavily Upon Theranostics - Cooperation Between Diagnostics and Pharmaceutical Sectors  2.4 The Human Genome Project Has Provided Important Scope for Pharmaceutical and Diagnostics Industries  2.4.1 Human Genome Project Marked Start of Genomic Era  2.4.2 Harnessing the Genomic Data is a Major Challenge for Science and Healthcare Industries for Many Years to Come  2.5 Biomarkers and Theranostics  2.5.1 Greater Understanding of Molecular Basis of Disease is Vital  2.5.2 Biomarkers Are Important for Determining Efficacy and Safety  2.5.3 The Scope of Biomarkers is Vast - The Search Will Intensify in the Years Ahead  2.6 Pharmacogenomics is Increasingly Relevant to Pharmaceutical Development 2.6.1 Genetic Variation and Response to Therapy  2.6.2 Molecular Technologies in Medical Science will Strongly Influence the Pharmaceutical and Molecular Diagnostics Sectors  2.6.3 The Number of Companies and Strategic Alliances is Increasing  2.7 Proteomics Constitutes the ``Next Step`` After Genomics  2.7.1 Applied Study of Protein Structure and Form is Important to Medical Developments  2.7.2 Elucidating the Relationship Between Genes and Proteins  2.8 Personalised Medicine Supported By Theranostics Could Supersede the Existing Blockbuster Model, With Sustainable Revenue Flows Continuing  2.8.1 Personalised Medicine Could Bring Significant Financial Gains for Diagnostics and Pharmaceutical Industries 2.8.2 Far-Sighted Pharma Companies are Looking Beyond the Present Technological and Commercial Challenges  2.9 Companies Are Gradually Changing Their Strategic Focus to Overcome Challenges in the Worldwide Healthcare Market  2.9.1 Product Life Cycle Management (PLM)  2.9.2 R&D Strategy is Crucial to Success  2.9.3 The Blockbuster "Model" Will Yield to More Segmented Product Development  2.10 Healthcare Stakeholders Can Benefit from Changes to Regulatory Processes  2.10.1 "Live" Licensing and "In-Life" Testing - The Way Forward?  2.10.2 Limited Approval Leading to Testing for Expanded License  2.10.3 Proposed Framework Could Bring Benefits to Patients While Aiding Drug Developers  2.11 There is an Expanding Market for In Vitro Diagnostics - Especially Molecular Diagnostics  2.11.1 Sales Potential for Increasingly Effective Diagnostic Agents is High 2.11.2 Personalised Medicine Will Not Necessarily Mark the End of High Revenues  2.11.3 The Demands of Treating Patient Sub-Populations Now a Prime Commercial Driver in Diagnostics and Pharmaceutical Industries  3 The World In Vitro Diagnostics Market 2013-2023 3.1 Significant Sales Growth Predicted for the Overall Global In Vitro Diagnostics Market from 2007 to 2023  3.1.1 IVD Market Led by Metabolism, Oncology and Infection Market Segments 3.1.2 Sales in Oncology Will Be Driven by Need for Early Detection and Determination of Efficacy  3.1.3 Metabolism and Oncology to Increase Market Shares in Overall IVD Market  3.2 Global IVD Market Breakdown by Principal Technology  3.2.1 High Growth for Nucleic Acid Testing  3.2.2 Nucleic Acid Testing is The Fastest Growing Segment of the Global Diagnostics Market  3.2.3 The Developing Role of Molecular Technologies in Clinical Diagnostics 3.2.4 Shift to Molecular Diagnostics with Drive for Personalised Medicine 3.2.5 Limitations to Revenue Growth in the IVD Market 3.2.6 Rise in Market for Diabetes Testing Products  3.2.7 Emerging Technologies Growing in Prominence from 2007 to 2023  3.2.8 Increasingly Important Role of IVD Technologies in Drug Discovery  3.2.9 Genetic Screening Sector has Great Potential as Emerging Technologyand Market  3.2.10 Growth Restrained by Pricing Ceilings and Downward Pressures on Healthcare Spending  3.3 Fast-Growing Technologies in the Nucleic Acid Market Segment  3.3.1 The Nucleic Acid Segment Contains Some of the Brightest Hopes for the IVD Market  3.3.2 DNA Probes Segment Will Show High Growth from 2007-2023  3.3.3 Nucleic Acid Testing in a Point-of-Care (POC) Setting  3.3.4 Impact of Molecular Medicine Provides a Significant Boost for Molecular Diagnostics  3.3.5 Importance of PCR-Based Technology  3.3.6 Clinical Genetic Testing Still Emergent  3.4 Personalised Medicine Will Become More Prominent in Healthcare With Theranostics Benefiting as a Result  3.4.1 Personalised Medicine in its Infancy but Still a Great Hope for Advancement of IVD Sector  3.4.2 Theranostics Aids Matching of Patients with Treatments - Helping to Optimise Efficacy and Safety  3.4.3 Greater Use of IVD Tests Could Significantly Reduce Adverse Drug Reactions and Cut Mortality Rates Associated With Drug Treatment  3.5 The Completion of the Human Genome Project Has Been a Major Driver of Molecular Diagnostics  3.5.1 Human Genome Sequencing has Made Matching of Therapy to Genetics and Phenotype a Possibility  3.5.2 High Gains for Developers and Marketers of Targeted Therapies and Supporting IVD Tests  3.6 Biomarker Technology is Still Emerging - But the Technological and Commercial Potential Remains Very Significant  3.6.1 Biomarker Use Increasingly Prevalent - but Long Way to Go Still 3.6.2 Biomarkers Key to Growth of IVD Market from Present Onwards  3.7 Protein Chip Technologies Gaining in Importance  3.7.1 Protein Chip Technologies in Molecular Diagnostics  3.7.2 What are the Advantages and Limitations of Protein Chip Technologies in Clinical Diagnostics?  3.7.3 Diagnostic Applications of Protein Chip Technologies  3.7.4 Which System Will Lead the Way for Diagnostic Protein Chip Technologies?  3.7.5 Cancer Diagnostics - The Key Field in the Future of Protein Chip Assays  4 Issues Affecting the Molecular Diagnostics Market  4.1 A SWOT Analysis for In Vitro Diagnostics  4.2 Diagnostics Companies Will Continue To Expand Their Presence in the Global Healthcare Industry  4.3 IVD Applications Face Some Commercial Obstacles  4.4 IVD is the Cornerstone of Personalised Medicine  4.4.1 Personalised Drugs are More Likely to Work Safely and Efficaciously  4.4.2 Advanced Screening for Disease Leading to Quicker Diagnoses  4.4.3 Improved Vaccines  4.4.4 Improvements in Drug Discovery and Reduced Cost of Clinical Trials  4.4.5 European Union IVD Directive (98/79/EC)  4.4.6 Medical Errors Cost the US Billions of Dollars  4.5 Theranostics will Benefit from FDA's Guidance on Pharmacogenomic Data Submission  4.5.1 Guidance On Pharmacogenomic Data Submission Will Accelerate The Development of Theranostics  4.5.2 Distinguishing Patients at a Greater Risk is Vital  4.5.3 In Future Parallel Use of Markers and Drugs Will Become Prevalent  4.6 Personalised Medicine is a Strong Driver of the IVD Sector  4.6.1 EDMA Cites Theranostics as a Medium-to-Long-Term Driver for Healthcare  4.6.2 Personalised Medicine Constitutes a New Chapter In Diagnostics  4.6.3 The Technology for Personalised Medicine Already Exists  4.7 Identifying Suitable Biomarkers Remains a Significant Challenge  4.8 Theranostics Bill Introduced in the US Senate During 2006  4.9 Development of Novel IVD Products May Be Limited by Low Reimbursement - Will Systems Change Advantageously?  4.10 Cancer Diagnostics is an Important Growth Area With Relevance to In Vitro Diagnostics - Especially Theranostics  4.
10.1 Cancer is the Main Developmental Area for Greater Use of In Vitro Diagnostics  4.10.2 Drivers of the Market for IVD and Therapeutics in Oncology 4.10.3 The Oncology Market also has some Restraints  4.11 Collaboration Among Stakeholders is Essential  4.12 Nucleic Acid Testing Technologies Will Be Decisive in the Development of the Theranostics Market  4.12.1 Nucleic Acid Amplification Techniques  4.12.2 Techniques are Presently Complicated  4.12.3 Biochips are Promising  4.12.4 Key Players Large and Small Making Gains in Nucleic Acid Testing  4.12.5 Prospects from Now Looking Forward  4.13 Primary Care and Personal Use of IVD  4.13.1 There is Definitely Scope for Greater Use  4.13.2 What Hurdles Must be Overcome for Point-of-Care IVD Technologies to Become Fully Established in Primary Care?  4.13.3 Personal Use of In Vitro Diagnostic Technologies  4.13.4 While Medical Stakeholders Will Benefit from Molecular Diagnostic and Other Applications of Genomics, Concerns Over Privacy Likely to Impede Progress  4.14 Barriers to the Growth of Pharmacogenomics  4.14.1 Pharmacogenomics Still an Emerging Field  4.14.2 The Complexity of Finding SNP Gene Variations that Affect Drug Responses  4.14.3 Limited Therapeutic Alternatives  4.14.4 Disincentives for Drug Companies to Develop and Produce Multiple Treatments for a Disease  4.14.5 Educating Healthcare Providers  4.15 Potential Changes to Pharma Regulatory and Developmental Processes Dependent upon IVD  4.15.1 Leading Industry Figures Call for More Flexible Approach to Drug Approval  4.15.2 Regulators Acknowledge the Need for Stratification of Treatment Populations  4.15.3 Visiongain Predicts Stratification of Patient Populations Leading to Live-Licensing/In-Life Testing  4.15.4 Stratification of Patients is Key to More Personalised Medicine Sought by Developers and Increasingly Required by Regulators  4.15.5 Traditional Clinical Development has a Significant Disadvantage - Better-Targeted Studies will Take Precedence  4.15.6 Evidence-Based Medicine will Become Increasingly Demanded by Pharma Stakeholders  4.16 Adaptive Clinical Trial Design Will Facilitate Interaction with Regulators and Provide Increased Rationalisation of Drug Development 4.16.1 Adaptive Clinical Trial Design Uses Accumulating Data  4.16.2 Regulators Should be Involved in the Process  4.16.3 Adaptive Trial Design will Gain Acceptance by Early Next Decade  4.17 Personalised Medicine Driven by Theranostics and Live Licensing/In-Life Testing Will Become Established by 2020  4.17.1 Drivers for Better-Targeted Medicine  4.17.2 The Prospects for More-Personalised Medicine and Related Diagnostics are Good  4.17.3 FDA Critical Path Initiative is a Progressive Move in the Right Direction  4.18 Personalised Medicine Aided by Regulatory Reform will also Face Significant Obstacles  4.18.1 The Complex, Disparate Pharma Industry Will Prove Difficult to Reform, Especially in a Revolutionary Manner  4.18.2 It is Unclear How Extensively New Clinical Testing Models and Supporting Regulation will be Applied  4.19 While Personalised Medicine and Better Targeted Clinical Trials are Emerging, Such Developments are Welcomed by the FDA and EMEA  4.19.1 Emerging Developments are Welcomed by Pharma Stakeholders  4.19.2 Cancer Drug Development Leads the Way in its Merging of Drug Development and Treatment of the Disease  4.19.3 FDA's Critical Path Initiative and Personalised Medicine 4.20 Pricing of Personalised Medicine 4.20.1 Personalised Medicine will Lead to Changes in Pricing and Reimbursement  4.20.2 Onus is on Companies to Prove Benefits of their Drugs Including Comparative Cost-Benefits  4.20.3 Biomarkers Can Create Value  4.20.4 The Developments are Complex and Systemic, Posing both Opportunities and Challenges for Healthcare Stakeholders  4.21 The Outlook for In Vitro Diagnostics is Exciting  5 Leading Players and Developments in the IVD Sector  5.1 Profiles of Some Important In Vitro Diagnostics Companies  5.1.1 Roche Diagnostics Division  5.1.2 Abbott Diagnostics  5.1.3 Gen-Probe Inc.  5.1.4 LifeScan Inc.  5.1.5 Axis-Shield  5.1.6 Clinical Data Inc and PGxHealth  5.1.7 Visible Genetics  5.1.8 NGI  5.2 Spotlight on Emerging Companies with High Promise in IVD Technologies 5.2.1 Proteome Sciences - Harnessing Proteomics  5.2.2 Investigen - Novel DNA Testing Applications  5.2.3 DxS Ltd - Facilitating Personalised Medicine  5.2.4 HBV Theranostica - IVD Solutions for Hepatitis B  5.2.5 Enigma Diagnostics - Exciting Developments in Rapid Detection  5.2.6 Itsi-Biosciences - Technology for Proteomics and Biomarker Discovery 5.2.7 Amorfix Life Sciences and Biogen Idec - an Important Partnership  5.2.8 MLT Research Ltd - Technologies Important to IVD  5.2.9 Innogenetics - Ambitious Programme in Theranostics  5.2.10 A&G Pharmaceutical - Solutions for Cancer Theranostics  5.3 Landmark Developments in Theranostics  5.3.1 Genentech's Herceptin and Novartis' Gleevec are Probably the Best Known  5.3.2 PharmaNetics' Thrombolytic Assessment System - Pioneers in the Field 5.3.3 Genentech and DakoCytomation: Herceptin and HercepTest  5.3.4 ImClone Systems and DakoCytomation: Erbitux and EGFR pharmDx Test  5.3.5 Abbott Laboratories' PathVysion HER-2 DNA Probe Kit  5.3.6 Bayer Diagnostics and Oncogene Science  5.3.7 Novartis and Ventana Medical Systems: Gleevec and VentanaDx c-Kit  5.4 Protein Chip Technologies for Clinical Diagnosis  5.4.1 ProteinChip by Ciphergen  5.4.2 Trinectin Proteome Chip by Phylos  5.4.3 Triage by Biosite  5.4.4 Tissue Microarray Technology  5.4.5 Molecular Diagnostics and Antigen-Antibody Interactions  6 In Vitro Diagnostic Sales in the Leading Developed and Developing Nations, 2007-2023  6.1 Expansion of the World Market Boosted by Increasing Sales in the Developing Healthcare Markets  6.1.1 High Sales in Developed Markets but India and China Catching Up  6.1.2 US to Lead World Market but Leading Developing Markets Exhibiting Highest Growth  6.2 Market Shares of Leading Nations for IVD Sales  6.2.1 US to Lose Market Share to India and China in Particular  6.3 There Will be High Sales Growth in Both Developed and Developing Markets for Diagnostics in the Years Ahead  6.3.1 US is Largest IVD Market  6.3.2 Potential for Sales Growth in Developing Countries is Significant 6.3.3 Improving Access to Modern Healthcare is a Principal Driver ofGrowth in Developing Nations  6.4 China and India are the Most Exciting New Prospects for the IVD Industry  6.4.1 China and India Both Have the Potential to be Leading Economic Nations  6.4.2 Strategies for Market Entry and Consolidation are Vital for Diagnostics Companies  6.5 WTO Agreements Affect Developments in Emerging Markets  6.5.1 The Principal Diagnostics Markets Remain the Leading Developed Nations But Developing Nations Are Increasingly Important  6.5.2 Expansion into Developing National Markets Will Help to Bring the IVD Industry to a New Level of Commercial Success  7 Theranostics Market Analysis, 2007-2023 7.1 Theranostic Products Will Constitute a Major Driver of the Global IVD Market  7.1.1 IVD Theranostics Market to Expand to Multi-Billion Dollar Sales by 2013  7.1.2 Drive for Personalised Medicine to Boost Theranostic Revenues  7.1.3 Fastest Growth in Cardiovascular & Respiratory and Oncology Segments 7.2 Market Share Gains in Prominent Market Segments  7.2.1 Cardiovascular & Respiratory and Oncology Segments to Gain Market Share from Present Onwards  7.2.2 CNS Segment to Lose Market Share from 2007 Onwards  7.3 Theranostics is Essentially a Fusion of Drug Therapy and Diagnostics 7.3.1 Diagnosis and Treatment Brought Closer Together  7.3.2 Reduction of ADRs  7.3.3 Narrowing of Gap Between Diagnostics and Pharmaceuticals  7.3.4 Recent Advances in Biomedical Sciences Have Made Theranostics  Possible  7.3.5 Genentech's Herceptin is a Prominent Example of the Theranostics  Approach  7.3.6 Recent FDA Publication Places Increasing Importance on Theranostics 7.4 Industry Has Been Relatively Slow to Adopt Theranostics - But That Situation Is Changing  7.4.1 Trends in Healthcare are Increasingly Favouring Theranostics 7.4.2 Will The Success of Theranostics Lead To a Shift in Spendin
g From Drugs to Diagnostics?  7.5 Theranostics Will Take Off In a Few Important Therapy Areas First 7.5.1 There are Exciting Possibilities for Theranostics  7.5.2 Cancer Diagnostic Technologies Constitute a Particularly Important Application  7.6 The Improvement in Clinical Performance from Theranostics Will Make It Easier To Justify Costs to Payers  7.6.1 Theranostics Can be a Win-Win for Diagnostics and Pharma Industries  7.6.2 A Theranostic Combination Can Provide an Important Competitive Advantage  7.7 Personalised Medicine Supported By Theranostics Could Supersede the Existing Blockbuster Model, With Sustainable Revenue Flows Continuing 7.7.1 Market is Expanding with Technology Flourishing  7.7.2 The Market for Theranostic Products Is Creating Significant Opportunities for Many Companies in the Pharmaceutical, Diagnostics and Biotechnological Sectors  7.7.3 Rising Health Insurance Coverage Will Benefit the Market  7.7.4 Inter-Industry Links Will Continue to Drive the Theranostics Market  7.7.5 Key Factors Required for Success in the Theranostics Market  8 Interviews with Industry Experts: In Vitro Diagnostics - Current and Future Trends  8.1 Interview 1: Director of a Diagnostics Company 8.1.1 Most Promising Therapeutic areas for IVD 8.1.2 Un-Met Medical Needs in IVD  8.1.3 Greatest Obstacles to Market Growth 8.1.4 Prospects for IVD Market Growth in the Developing Nations 8.1.5 Prospects for Theranostics 8.2 Interview 2: CEO of a Diagnostics Company  8.2.1 Most Promising Therapeutic areas for IVD  8.2.2 Un-Met Medical Needs in IVD  8.2.3 Greatest Obstacles to Market Growth  8.2.4 Prospects for IVD Market Growth in the Developing Nations  8.2.5 Prospects for Theranostics  8.3 Interview 3: Director of a Diagnostics Company  8.3.1 Most Promising Therapeutic areas for IVD  8.3.2 Un-Met Medical Needs in IVD  8.3.3 Greatest Obstacles to Market Growth  8.3.4 Prospects for IVD Market Growth in the Developing Nations  8.3.5 Prospects for Theranostics  8.4 Interview 4: Business Development Director of a Diagnostics Company 8.4.1 Most Promising Therapeutic areas for IVD  8.4.2 Un-Met Medical Needs in IVD  8.4.3 Greatest Obstacles to Market Growth  8.4.4 Prospects for IVD Market Growth in the Developing Nations  8.4.5 Prospects for Theranostics  8.5 Responses from a KOL Survey on Theranostics  8.5.1 How Influential Will Theranostics Be In Coming Years?  8.5.2 Comment on Responses  8.5.3 Are Pharmaceutical and Diagnostic Companies Ready for Closer Links? 8.5.4 Comment on Responses  8.5.5 Will Theranostics Contribute Significantly to Clinical Trials? 8.5.6 Visiongain Comment on Responses  8.5.7 In What Areas Will Theranostics Be Most Prominent? 8.5.8 Visiongain Comment on Responses  9 Conclusions  9.1 In Vitro Diagnostics are Vital to Clinical Decision Making  9.2 Significant Growth of In Vitro Diagnostics Market from 2007 to 2023 9.3 Personalised Medicine Will Rely Heavily Upon Theranostics - Cooperation Between Diagnostics and Pharmaceutical Sectors  9.4 Expansion of the World Market Boosted by Increasing Sales in the Developing Healthcare Markets  9.5 Expansion into Developing National Markets and Lifestyle Diseases Will Drive Market  Appendices  Appendix A: Glossary  Appendix B: Notes on FDA Classification and Regulation of IVD Applications Appendix C: EC Classification of In Vitro Diagnostic Medical Devices  Appendix D: In Vitro Diagnostics: Prominent Companies  Appendix E: About visiongain  Appendix F: Visiongain report evaluation form  List of Tables  Table 3.1 Sales ($bn) for the World In Vitro Diagnostic Market by Disease Area, 2007-2013  Table 3.2 Sales ($bn) for the World In Vitro Diagnostic Market by Disease Area, 2014-2020  Table 3.3 CAGR (%) for the World In Vitro Diagnostic Market by Disease Area, 2007-2020  Table 3.4 World IVD Market by Disease Area: Long Range Sales Forecasts ($bn) with CAGR (%), 2007-2023  Table 3.5 Market Share (%) for the World In Vitro Diagnostic Market by Disease Area, 2007, 2014, 2018 and 2023  Table 3.6 Sales ($bn) for the World In Vitro Diagnostic Market by Principal Technology, 2007-2013  Table 3.7 Sales ($bn) for the World In Vitro Diagnostic Market by Principal Technology, 2014-2020  Table 3.8 CAGR (%) for the World In Vitro Diagnostic Market by Principal Technology, 2007-2020  Table 3.9 World In Vitro Diagnostic Market by Principal Technology: Long Range Sales Forecasts ($bn) with CAGR (%), 2007-2023  Table 3.10 Market Share (%) for the World In Vitro Diagnostic Market by Principal Technology, 2007, 2014, 2018 and 2023  Table 3.11 Sales ($bn) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2007-2013  Table 3.12 Sales ($bn) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2014-2020  Table 3.13 CAGR (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2007-2020  Table 3.14 Nucleic Acids Segment of the World IVD Market by Sub Technology: Long Range Sales Forecasts ($bn) with CAGR (%), 2007-2023  Table 3.15 Market Share (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2007, 2014, 2018 and 2023  Table 4.1 A SWOT Chart for In Vitro Diagnostic Applications, 2008-2023 Table 4.2 Greater Use of Disease Knowledge and Biomarkers Will Benefit Pharmaceutical Development  Table 6.1 Sales ($bn) for the World In Vitro Diagnostic Market by Leading Nation, 2007-2013  Table 6.2 Sales ($bn) for the World In Vitro Diagnostic Market by Leading Nation, 2014-2020  Table 6.3 CAGR (%) for the World In Vitro Diagnostic Market by Leading Nation, 2007-2020  Table 6.4 World In Vitro Diagnostic Market by Leading Nation: Long Range Sales Forecasts ($bn) with CAGR (%), 2007-2023  Table 6.5 Market Share (%) for the World In Vitro Diagnostic Market by Leading Nation, 2007, 2014, 2018 and 2023  Table 7.1 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2007-2013  Table 7.2 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2014-2020  Table 7.3 CAGR (%) for the World IVD Theranostics Market by Disease Area, 2007-2020  Table 7.4 World IVD Theranostics Market by Disease Area: Long Range Sales Forecasts ($bn) with CAGR (%), 2007-2023  Table 7.5 World IVD Theranostics Market Sales Compared With Overall IVD Market ($bn), Market Share (%) and CAGR (%), 2007-2023  Table 7.6 Market Share (%) for the World IVD Theranostics Market by Disease Area, 2007, 2014, 2018 and 2023  List of Figures  Figure 1.1 Total Sales ($bn) for the World In Vitro Diagnostic Market, 2007-2020  Figure 2.1 The Drug Development Process is Long, Complex and Costly  Figure 3.1 Sales ($bn) for the World In Vitro Diagnostic Market by Disease Area, 2007-2013  Figure 3.2 Total Sales ($bn) for the World In Vitro Diagnostic Market, 2007-2013  Figure 3.3 Sales ($bn) for the World In Vitro Diagnostic Market by Disease Area, 2014-2020  Figure 3.4 Total Sales ($bn) for the World In Vitro Diagnostic Market, 2014-2020  Figure 3.5 Market Share (%) for the World In Vitro Diagnostic Market by Disease Area, 2007  Figure 3.6 Market Share (%) for the World In Vitro Diagnostic Market by Disease Area, 2014  Figure 3.7 Market Share (%) for the World In Vitro Diagnostic Market by Disease Area, 2018  Figure 3.8 Market Share (%) for the World In Vitro Diagnostic Market by Disease Area, 2023  Figure 3.9 Sales ($bn) for the World In Vitro Diagnostic Market by Principal Technology, 2007-2013  Figure 3.10 Sales ($bn) for the World In Vitro Diagnostic Market by Principal Technology, 2014-2020  Figure 3.11 Market Share (%) for the World In Vitro Diagnostic Market by Principal Technology, 2007  Figure 3.12 Market Share (%) for the World In Vitro Diagnostic Market by Principal Technology, 2014  Figure 3.13 Market Share (%) for the World In Vitro Diagnostic Market by Principal Technology, 2018  Figure 3.14 Market Share (%) for the World In Vitro Diagnostic Market by Principal Technology, 2023  Figure 3.15 Sales ($bn) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2007-2013  Figure 3.16 Total Sales ($bn) for the Nucleic Acids Segment of the WorldIVD Market, 2007-2013  Figure 3.17 Sales ($bn) for the Nucleic Acids Segment of the World IVD Market by S
ub Technology, 2014-2020  Figure 3.18 Sales ($bn) for the Nucleic Acids Segment of the World IVD Market, 2014-2020  Figure 3.19 Market Share (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2007  Figure 3.20 Market Share (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2014  Figure 3.21 Market Share (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2018  Figure 3.22 Market Share (%) for the Nucleic Acids Segment of the World IVD Market by Sub Technology, 2023  Figure 4.1 How Pharmaceutical Development Will Evolve into a More Progressive System  Figure 4.2 The Dynamic Integrated Regulatory System of the Future Figure 4.3 Systemic Changes to Pharmaceutical Regulation Involve all Healthcare Stakeholders  Figure 6.1 Sales ($bn) for the World In Vitro Diagnostic Market by Leading Nation, 2007-2020  Figure 6.2 Sales ($bn) for the World In Vitro Diagnostic Market by Leading Nation, 2007-2020 (Continued)  Figure 6.3 Market Share (%) for the World In Vitro Diagnostic Market by Leading Nation, 2007  Figure 6.4 Market Share (%) for the World In Vitro Diagnostic Market by Leading Nation, 2014  Figure 6.5 Market Share (%) for the World In Vitro Diagnostic Market by Leading Nation, 2018  Figure 6.6 Market Share (%) for the World In Vitro Diagnostic Market by Leading Nation, 2023  Figure 7.1 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2007-2013  Figure 7.2 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2007-2013 (Continued)  Figure 7.3 Total Sales ($bn) for the World IVD Theranostics Market, 2007-2013  Figure 7.4 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2014-2020  Figure 7.5 Sales ($bn) for the World IVD Theranostics Market by Disease Area, 2014-2020 (Continued)  Figure 7.6 Total Sales ($bn) for the World IVD Theranostics Market, 2014-2020  Figure 7.7 World IVD Theranostics Market Sales Compared With Overall IVD Market ($bn), 2007, 2018 and 2023  Figure 7.8 Total IVD Theranostics Share (%) of World IVD Market, 2007, 2018 and 2023  Figure 7.9 Market Share (%) for the World IVD Theranostics Market by Disease Area, 2007  Figure 7.10 Market Share (%) for the World IVD Theranostics Market by Disease Area, 2014  Figure 7.11 Market Share (%) for the World IVD Theranostics Market by Disease Area, 2018  Figure 7.12 Market Share (%) for the World IVD Theranostics Market by Disease Area, 2023 More Details Companies Listed  3M  A&G Pharmaceutical  Abbott Diagnostics  Abbott Laboratories  Affymetrix  Agendia  Agilent Technologies Inc.  American Diagnostica  Amorfix Life Sciences  Applera Corporation  Applied Biosystems  Applied Imaging  Apria Healthcare  Arcturus  ARKRAY Incorporated  AstraZeneca  Athena Diagnostics  Axis-Shield  Baxter International Inc.  Bayer  Bayer Diagnostics  Beckman Coulter  Becton Dickinson  Binax Incorporated  Biogen Idec  BioMerieux  Bio-Rad Laboratories Incorporated  Biosite  Bristol-Myers Squibb  Cambridge Theranostics  CanAg Diagnostics  Celera Diagnostics, see Applera Corporation  Chiron  Ciphergen Biosystems  Clarient  Clinical Data Inc.  Competitive Technologies  CyGene  Cytyc  Dade Behring  DakoCytomation  Del Mar Reynolds Medical Ltd.  Diagnostic Products Corporation  Diagnostic Systems Laboratories  Digene Corporation  DNAPrint Genomics  DxS Ltd  Enigma Diagnostics Ltd  Epigenomics  EXACT Sciences  First Check Diagnostics  Fisher Scientific  Fornix Theranostics  Fresenius Medical Care  Fujirebio Diagnostics  Gambro AB  GE Healthcare  Gemini (Eurona)  Genaissance Pharmaceuticals  Genentech  GeneOhm Sciences  General Nutrition Centers Inc.  Genetic Vectors  Gen-Probe Inc.  Gentiva Health Services Inc.  Genzyme  Glaxo Wellcome  Graham-Field Health Products  HBV Theranostica  Health Discovery  HealthGrades  Hypoguard USA  Hyseq  IGEN International  ImClone Systems  Innogenetics  Intronn Inc.  Invacare Corporation  Inverness Medical Innovations  Investigen  Invitrogen Corporation  Itsi-Biosciences  Johnson & Johnson  Kingo Diagnostika  LabCorp  Lifescan Inc.  Lincare  Lpath Therapeutics  Lumigen  Matria Healthcare  MDY Healthcare plc  Medisys plc  Merck & Co.  Merck KGaA  Millennium Predictive Medicine  MLT Research Ltd  Monogram Biosciences  Myriad Genetics Inc.  Neighborhood Connections  NGI  Nova Biomedical Corporation  Novartis  Olympus Corporation  Oncogene Sciences  Oncomethylome Sciences  Organon Teknika  Orion Genomics  Ortho-Clinical Diagnostics  Pathwork Informatics  PeptiFarma  PerkinElmer Incorporated  PGxHealth  PharmaNetics  Phylos  Power3 Medical  Primagen  Primus Corporation  Pronto Diagnostics  Proteome Sciences  Provalis  QIAGEN NV  Quest Diagnostics  Quidel  Ranbaxy Laboratories  Respironics  Response Biomedical  Roche  Rubicon Genomics  Seapro Theranostics International B.V  Sequenom  Siemens Medical Solutions  Sunrise Medical  TheraNostics GmbH  Thermo Electron  Tibotec-Virco  Trinity Biotech plc  TriPath Imaging Inc.  Ventana Medical Systems  Veridex LLC  Veri-Q Inc.  Visible Genetics  Vysis Inc.  Wyeth 

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Cosmederm Technologies, a specialty pharmaceutical company focused on dermatology and aesthetic medicine, has signed a licensing and distribution agreement with Dr Reddy’s Laboratories.

The agreement grants Dr Reddy’s exclusive rights to distribute Cosmederm Technologies’s unique skin care products throughout India.

Cosmederm’s proprietary technology allows for the formulation of highly potent, non-irritating skin care products in the areas of anti-aging, acne, pruritus, rosacea and others. The partnership is for two product lines – Refinity peel kits (Glycolic acid 70%) and Cosmederm peel kits (Glycolic acid 50%).

Through this partnership Dr Reddy’s is said to enter the aesthetic dermatology segment and consolidates its position in cosmeceuticals.

Sean Edwards, president of Cosmederm Technologies, said: “The opportunity to work with Dr Reddy’s and introduce our products to Indian consumers is a great milestone for Cosmederm. As a global brand, Dr Reddy’s is a very valuable partner.”

North American Scientific, a developer of radiation therapy devices, has signed a definitive agreement to sell its non-therapeutic product line to Eckert & Ziegler Isotope Products.

The product line includes radiation sources and standards used in a variety of areas for calibration, measurement, analysis and control.

The transaction is valued at approximately $6 million and is subject to customary conditions with an expected close by September 5, 2008.

John Rush, President and CEO of North American Scientific, said: “This divestiture allows us the opportunity to focus solely on growing the therapeutic areas of our business with our Prospera and ClearPath product lines for local radiation treatment for the prostate and breast cancer patient, while also providing the company with important non-dilutive capital to invest in ongoing operations.”

CIGNA has named Dr. Charles Smith as chief medical officer for CIGNA’s health solutions unit, which provides the company’s health and wellness programs, including health coaching, behavioral health and lifestyle management programs, case management and chronic condition management. In this role, Dr. Smith will be responsible for the unit’s clinical policies, clinical strategic direction and leadership for the unit’s physicians.

Dr. Smith has more than 20 years of experience developing comprehensive health and wellness strategies that emphasize prevention and employee engagement. Most recently he served as a principal for Towers Perrin’s Health and Welfare practice in New York.

“Charlie will help ensure that all our health improvement programs produce meaningful, evidenced-based outcomes for the individuals that use them,” said Keith Dixon, president of CIGNA’s health solutions unit. “He is widely recognized as a national leader in health services, and will be on point to articulate our clinical support capabilities both within the industry and with the public.”

Dr. Smith is returning to CIGNA, where from 1999 through 2007 he held various medical leadership positions, most recently serving as national medical officer for CIGNA HealthCare national accounts. Prior to CIGNA, he served as senior medical director for NYLCare Health Plans of the Gulf Coast, medical director for Prudential Health Plans, Houston and for FHP Health Plans in San Diego, as well as a staff physician with Kelsey-Seybold Clinics in Houston.

He received a bachelor’s degree from Texas Tech University and both medical and family practice degrees from the University of Texas Health Science Center, Houston.

About CIGNA

CIGNA (NYSE:CI) provides employers with benefits, expertise and services that improve the health, well-being and security of their employees. With approximately 47 million covered lives in the United States and around the world, CIGNA’s operating subsidiaries offer a full portfolio of medical, dental, behavioral health, pharmacy and vision care benefits and group life, accident and disability insurance. www.cigna.com.

NEWTOWN, Pa., Sept. 4 /PRNewswire/ — CapMed (http://www.capmed.com/), a division of Bio-Imaging Technologies, Inc. , and provider of interactive personal health management solutions, today announced that it will begin offering “smart messaging” to users of its award-winning Personal Health Record (PHR) through a gaps-in-care protocol engine within the PHR. The gaps-in-care engine analyzes both user-entered and electronically provided personal health information to notify users of needed care or to trigger information alerts within the PHR.

“Smart messaging supports CapMed’s ongoing commitment to engage users in better health management by providing solutions that are both personal and actionable, enhancing PHR for both consumers and our partners such as health plans, employers and hospitals,” said Wendy Angst, General Manager of CapMed. “Structured around a comprehensive review of PHR information using nationally recognized guidelines, smart messaging delivers quality support to individuals and care team members, ensuring that preventive and follow-up care are completed on schedule.”

Users of CapMed’s PHR receive personally relevant information on treatment options, providers, support groups, clinical trials, medication recalls, alerts for values out of normal range data and reminders for continued care. For example, a 55-year-old woman would receive reminders to make her annual mammogram appointment based on the date of her previous exam, while a patient with diabetes would receive an alert to schedule foot and eye exams even if no previous records of eye and foot exams were present within the PHR.

CapMed’s smart messaging can be sent directly to a user of CapMed’s PHR and displayed on their PHR dashboard (a dashboard view of health status and action items), sent via secure email, or text messaged to a mobile phone. With the user’s permission, messages can also be sent to a user’s physician or other care team members. CapMed messages often contain live links that enable the user to refill a medication, schedule a test or simply review additional health content.

CapMed’s smart messaging is powered by a gaps-in-care protocol engine, which is focused on best practice clinical guidelines. The engine compares available data against nationally recognized electronic health guidelines to produce evidence-based messaging on an individual’s health status.

About CapMed

CapMed, a division of Bio-Imaging Technologies, Inc., is the cornerstone of Bio-Imaging’s Personal Health Management Division. CapMed is the leading provider of personal health management solutions for hospitals and health systems, providers, managed care, employers and pharmaceutical companies, with more than 600,000 distributed to date. These solutions enable patients to monitor and manage their health and to improve communications with care providers, ultimately improving outcomes and reducing costs of care and are available in multiple formats: onlinePHR, icePHR, icePHR Mobile, desktopPHR, and the Personal HealthKey. CapMed offers custom development to organizations who want to add unique or proprietary capabilities to the platform. For more information on the CapMed Personal Health Management Solutions, please visit http://www.capmed.com/.

About Bio-Imaging Technologies, Inc.

Bio-Imaging Technologies, Inc. is a healthcare contract service organization providing services that support the product development process of the pharmaceutical, biotechnology and medical device industries. The Company has specialized in assisting its clients in the design and management of the medical-imaging component of clinical trials since 1990. Bio-Imaging serves its clients on a global basis through its Core Labs in Newtown, PA, and Leiden, The Netherlands, along with business offices in PA, MA, The Netherlands, Germany and France. Phoenix Data Systems, Inc., a subsidiary of Bio-Imaging Technologies, is a leading global clinical data services provider of electronic data capture (EDC) services and a comprehensive array of broadly interoperable eClinical data solutions to the pharmaceutical and biotechnology industries. Phoenix Data Systems delivers full service EDC, a unique combination of electronic data capture, interactive voice response, reporting, and data management solutions. Through its CapMed Personal Health Management Suite, Bio-Imaging provides its Personal HealthKey* technology, the Personal Health Record (PHR) software, and CapMed Patient Portal allowing patients to better monitor and manage their health care information. Additional information about Bio-Imaging is available at http://www.bioimaging.com/.

Certain matters discussed in this press release are “forward-looking statements” intended to qualify for the safe harbors from liability established by the Private Securities Litigation Reform Act of 1995. In particular, the Company’s statements regarding trends in the marketplace and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the consummation and the successful integration of current and proposed acquisitions, the timing of projects due to the variability in size, scope and duration of projects, estimates and guidance made by management with respect to the Company’s financial results, backlog, critical accounting policies, regulatory delays, clinical study results which lead to reductions or cancellations of projects, and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein and expressed from time to time in the Company’s filings with the Securities and Exchange Commission could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance. You should review the Company’s filings, especially risk factors contained in the Form 10-K and the recent form 10-Q.

   Company Contact:   CapMed   Wendy Angst, General Manager   (267) 757-3000    Media Inquires:   KNB Communications   Christopher Capot   (212) 505-2441    Investor Relations:   Porter, Levay, and Rose   Linda Decker   (212) 564-4700  

CapMed

CONTACT: Wendy Angst, General Manager of CapMed, +1-267-757-3000; orMedia Inquires: Christopher Capot of KNB Communications, +1-212-505-2441; orInvestor Relations: Linda Decker of Porter, Levay, and Rose, +1-212-564-4700,both for CapMed

Web site: http://www.capmed.com/http://www.bioimaging.com/

Tenet Healthcare Corporation (NYSE:THC) today announced that 38 of the hospitals it operates have received 214 quality designations through CIGNA HealthCare, a subsidiary of CIGNA Corporation (NYSE:CI).

These quality designations are based on outcomes for treatment of 29 surgical procedures and medical conditions. The patient outcomes data are in part based on a hospital’s Centers for Medicare & Medicaid Services (CMS) Hospital Compare measures, Leapfrog Patient Safety Measures, and their mortality and complication rates. The designations indicate superior outcomes and about 57 percent of CIGNA HealthCare’s network hospitals receive a quality designation for treatment of at least one condition.

“These designations provide evidence of our hospitals’ commitment to providing high quality care,” said Stephen L. Newman, M.D., Tenet’s chief operating officer and interim chief medical officer. “Such recognitions demonstrate that our hospitals and staff deliver care that exceeds nationally recognized standards for the specific condition. In fact, 76 percent of Tenet’s hospitals received a CIGNA HealthCare quality designation. We also have increased the total number of designations at our hospitals from 134 in 2007 to 214 in 2008, a 60 percent increase.”

In addition to these quality designations, 21 Tenet hospitals have received 60 Center of Excellence (COE) designations for 2008 from CIGNA HealthCare. These COE classifications mean that the hospitals met CIGNA HealthCare’s high standards for quality and efficiency.

“Our goal is to provide individuals with valuable information regarding those hospital programs that achieve both superior quality outcomes and superior affordability,” said Dick Salmon, M.D., Ph.D., senior national medical director at CIGNA HealthCare. “The Centers of Excellence designations are readily available to patients who use CIGNA Care Connections, an integrated online provider directory or through CIGNA HealthCare’s clinical resources such as 24 Health Information Line nurses.”

The 38 Tenet hospitals receiving the quality and Center of Excellence designations for 2008 are:

— Atlanta Medical Center, Atlanta, Ga., (2) – Gastric Bypass and Spinal Fusion

— Brookwood Medical Center, Birmingham, Ala., (5) – Angioplasty, Coronary Artery Bypass Graft*, Colon Surgery, Total Hip Replacement and Total Knee Replacement

— Central Carolina Hospital, Sanford, N.C., (2) – Laparoscopic Gall Bladder Removal and Stroke*

— Coral Gables Hospital, Coral Gables, Fla., (3) – Laparoscopic Gall Bladder Removal, Total Hip Replacement and Total Abdominal Hysterectomy

— Creighton University Medical Center, Omaha, Neb., (2) – Angioplasty and Heart Attack

— Cypress Fairbanks Medical Center, Houston, Texas, (6) – Laparoscopic Gall Bladder Removal*, Gastric Bypass*, Heart Attack*, Adult Pneumonia, Stroke and Vaginal Delivery

— Delray Medical Center, Delray Beach, Fla., (11) – Angioplasty, Coronary Artery Bypass Graft, Cardiac Pacemaker Implant, Colon Surgery, Adult Craniotomy, GI Hemorrhage, Heart Attack, Heart Failure, Total Hip Replacement, Irregular Heartbeat and Adult Pneumonia

— Des Peres Hospital, St. Louis, Mo., (7) – Angioplasty*, Coronary Artery Bypass Graft*, Heart Failure, Total Hip Replacement, Total Knee Replacement, Adult Pneumonia and Spinal Fusion*

— Desert Regional Medical Center, Palm Springs, Calif., (6) – Angioplasty*, Coronary Artery Bypass Graft, Caesarean Section, Total Hip Replacement, Total Knee Replacement* and Adult Pneumonia

— Doctors Medical Center, Modesto, Calif., (2) – Coronary Artery Bypass Graft and Vaginal Delivery

— East Cooper Hospital, Mt. Pleasant, S.C., (1) – Spinal Fusion

— Florida Medical Center, Ft. Lauderdale, Calif., (9) – Angioplasty, Cardiac Catheterization, Cardiac Pacemaker Implant, Laparoscopic Gall Bladder Removal, Heart Attack, Heart Failure, Total Hip Replacement, Adult Pneumonia and Stroke

— Fountain Valley Regional Hospital and Medical Center, Fountain Valley, Calif., (10) – Cesarean Section*, Angioplasty*, Gastric Bypass, GI Hemorrhage, Heart Attack, Heart Failure, Total Abdominal Hysterectomy, Adult Pneumonia, Stroke and Vaginal Delivery*

— Frye Regional Medical Center, Hickory, N.C., (7) – Cesarean Section*, Coronary Artery Bypass Graft, Colon Surgery, Laparoscopic Gall Bladder Removal*, Total Knee Replacement*, Spinal Fusion* and Vaginal Delivery

— Good Samaritan Medical Center, West Palm Beach, Fla., (5) – Heart Attack, Heart Failure, Adult Pneumonia, Stroke* and Vaginal Delivery

— Hahnemann University Hospital, Philadelphia, Pa., (5) – Cardiac Catheterization, Heart Failure, Adult Pneumonia, Stroke and Vaginal Delivery

— Hialeah Hospital, Hialeah, Fla., (11) – Caesarean Section, Chronic Obstructive Pulmonary Disease, Laparoscopic Gallbladder Removal, Gastric Bypass*, Heart Attack, Heart Failure, Total Abdominal Hysterectomy, Adult Pneumonia, Stroke and Vaginal Delivery

— Hilton Head Hospital, Hilton Head, S.C., (2) – Angioplasty and Total Hip Replacement

— Houston Northwest Medical Center, Houston, Texas, (11) – Angioplasty*, Coronary Artery Bypass Graft*, Cardiac Catheterization, Colon Surgery*, Adult Craniotomy*, Laparoscopic Gall Bladder Removal*, Head and Neck Endarterectomy*, Heart Attack, Adult Pneumonia, Stroke and Vaginal Delivery*

— Lake Pointe Medical Center, Rowlett, Texas, (2) – Laparoscopic Gall Bladder Removal* and Vaginal Delivery*

— Lakewood Regional Medical Center, Lakewood, Calif., (6) – Angioplasty*, Coronary Artery Bypass Graft*, Heart Failure, Total Hip Replacement*, Adult Pneumonia and Stroke

— Los Alamitos Medical Center, Los Alamitos, Calif., (5) – Caesarean Section*, Colon Surgery, Heart Failure, Stroke and Vaginal Delivery*

— North Fulton Regional Hospital, Roswell, Ga., (4) – Heart Attack, Heart Failure, Total Hip Replacement and Adult Pneumonia

— North Shore Medical Center, Miami, Fla., (6) – Caesarean Section, Heart Attack, Heart Failure, Adult Pneumonia, Stroke and Vaginal Delivery

— Palm Beach Gardens Medical Center, Palm Beach Gardens, Fla., (13) – Angioplasty*, Coronary Artery Bypass Graft*, Cardiac Catheterization*, Cardiac Pacemaker Implant, Laparoscopic Gall Bladder Removal, Head & Neck Endarterectomy, Heart Attack*, Heart Failure*, Heart Valve Replacement*, Total Hip Replacement, Total Knee Replacement, Adult Pneumonia and Spinal Fusion*

— Palmetto General Hospital, Hialeah, Fla., (8) – Caesarean Section, Laparoscopic Gallbladder Removal, Gastric Bypass, Heart Attack, Total Abdominal Hysterectomy, Total Knee Replacement, Stroke and Vaginal Delivery

— Park Plaza Hospital, Houston, Texas, (8) – Caesarean Section, Laparoscopic Gall Bladder Removal, Gastric Bypass*, Heart Failure, Total Abdominal Hysterectomy*, Adult Pneumonia, Stroke and Vaginal Delivery

— Piedmont Medical Center, Rock Hill, S.C., (4) – Colon Surgery, Total Hip Replacement, Total Knee Replacement and Adult Pneumonia

— Placentia-Linda Hospital, Placentia, Calif., (6) – Cesarean Section*, Laparoscopic Gall Bladder Removal*, Total Hip Replacement*, Total Knee Replacement*, Adult Pneumonia and Vaginal Delivery*

— Saint Francis Hospital, Memphis, Tenn., (6) – Angioplasty*, Coronary Artery Bypass Graft,* Colon Surgery*, Gastric Bypass, Head and Neck Endarterectomy* and Total Knee Replacement*

— Saint Louis University Hospital, St. Louis, Mo., (2) – Heart Failure and Stroke*

— San Ramon Regional Medical Center, San Ramon, Calif., (4) – Caesarean Section, Colon Surgery, Adult Pneumonia and Vaginal Delivery

— Sierra Vista Regional Medical Center, San Luis Obispo, Calif., (6) – Adult Craniotomy, Disk Surgery, Laparoscopic Gall Bladder Removal, Total Hip Replacement, Spinal Fusion* and Vaginal Delivery

— South Fulton Medical Center, East Point, Ga., (3) – Heart Attack, Heart Failure and Stroke

— Spalding Regional Medical Center, Griffin, Ga., (3) – Heart Failure, Adult Pneumonia and Stroke

— St. Mary’s Medical Center, West Palm Beach, Fla., (7) – Caesarean Section, Adult Craniotomy, Heart Attack, Heart Failure, Adult Pneumonia, Stroke and Spinal Fusion

— Twin Cities Community Hospital, Templeton, Calif., (6) – Cesarean Section*, Colon Surgery, Laparoscopic Gall Bladder Removal, Total Hip Replacement, Total Knee Replacement* and Vaginal Delivery

— West Boca Medical Center, Boca Raton, Fla., (8) – Caesarean Section, Laparoscopic Gall Bladder Removal, Heart Attack*, Heart Failure*, Total Abdominal Hysterectomy, Adult Pneumonia*, Stroke* and Vaginal Delivery

* Indicates CIGNA HealthCare COE Designation

In addition, the two companies have agreed to develop an innovative pay-for-performance program. “This exciting program encourages the continued improvement in quality and efficiency at Tenet’s hospitals,” said Clint Hailey, Tenet’s senior vice president and chief managed care officer. “The new program is likely to include CIGNA HealthCare’s existing COE designations, quality designations, hospital patient satisfaction scores and readmission rates, as well as other measures. By meeting the criteria established by the pay-for-performance program, Tenet’s hospitals may receive incremental revenue.”

CIGNA HealthCare’s Dr. Salmon added, “The opportunity to advance a program that rewards for improvement and achievement in superior quality outcomes and affordability is exciting. This reinforces CIGNA HealthCare’s mission to improve the health, well-being and security of those we serve by encouraging providers like Tenet to maintain and improve their efficiencies, quality and patient satisfaction.”

Tenet Healthcare Corporation, through its subsidiaries, owns and operates acute care hospitals and related ancillary health care businesses, which include ambulatory surgery centers and diagnostic imaging centers. Tenet is committed to providing high quality care to patients in the communities we serve. Tenet can be found on the World Wide Web at www.tenethealth.com.

About CIGNA HealthCare

CIGNA HealthCare, a health service organization based in Bloomfield, CT, works to improve the health, well-being and security of the people we serve. A leading provider of employee benefit services and programs, CIGNA HealthCare offers a broad array of medical, dental, behavioral health, and pharmacy benefits plans and coverage. We also build and provide health and wellness coaching programs and consumer information tools designed to improve health and help people in their health care decision-making. “CIGNA HealthCare” and the “Tree of Life” logo are registered service marks of CIGNA Intellectual Property, Inc., licensed for use by CIGNA Corporation (NYSE:CI) and its operating subsidiaries, including Connecticut General Life Insurance Company. All products and services are provided exclusively by such operating subsidiaries, and not by CIGNA Corporation. For more information, visit www.cigna.com.

Some of the statements in this release may constitute forward-looking statements. Such statements are based on our current expectations and could be affected by numerous factors and are subject to various risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including our annual report on Form 10-K for the year ended Dec. 31, 2007, our quarterly reports on Form 10-Q and periodic reports on Form 8-K. Do not rely on any forward-looking statement, as we cannot predict or control many of the factors that ultimately may affect our ability to achieve the results estimated. We make no promise to update any forward-looking statement, whether as a result of changes in underlying factors, new information, future events or otherwise.

NAPA, Calif., Sept. 4 /PRNewswire-FirstCall/ — Senetek PLC (BULLETIN BOARD: SNKTY) , a life sciences company engaged in the development of technologies that target the science of healthy aging, announced today the launch of Pyratine-6(TM), representing the next generation of superior skincare products for the correction of visible signs of aging. In the 1990’s Senetek developed kinetin, the cytokinin-based active ingredient in the successful Kinerase skincare line, and are now taking cytokinin technology further with Pyratine-6(TM).

Pyratine-6(TM)’s new cytokinin technology works faster than kinetin or any other product on the market in dramatically reducing roughness and redness starting in as little as two weeks, with full results on fine wrinkles, dryness, discoloration, and other signs of photodamage in twelve weeks of consistent use. Clinical studies showed improvement in pre-existing redness associated with rosacea, eczema, contact dermatitis and menopause.

Cytokinins are natural plant-derived growth factors that stimulate growth and differentiation. While they do not stimulate proliferation of human cells, cytokinins have proved to be superior anti-aging agents in skin cells. By functioning as antioxidants, they purge cellular debris and delay the aging process. The enhanced Pyratine-6(TM) cytokinin is the most effective and fastest acting cytokinin available today.

In a clinical study of 34 patients, Pyratine-6(TM) was well tolerated by 33 of the patients. Because it is non-acidic and without irritants, Pyratine-6(TM) shows 0 on a 4-point scale of irritation and can be used in conjunction with treatment procedures such as chemical peels, laser resurfacing, microdermabrasion and injectables. It has no know interactions with drugs or other products and, it can be used before the application of cosmetics and in conjunction with sunscreen and other enhancement products.

In an independent study by Dr. Jerry L. McCullough from the University of California, Irvine, et al published in the February 2008 Journal of Drugs in Dermatology, Dr. McCullough stated, “Treatment with Pyratine-6(TM) (0.1%) over 12 weeks improves roughness and skin moisturization in 2 weeks and hyperpigmentation and fine wrinkles in 4 weeks.” Further, the report stated that adverse effects of Pyratine-6(TM) are “minimal” and “transient.”

Pyratine-6(TM) will be available starting in September 2008 only through dermatologists, plastic surgeons and top medical spas across the country, providing its high efficacy and specialized benefits in a professional environment. For a list of physicians and medical spas carrying Pyratine-6(TM) call 888-GO-PYRATINE or 877-586-3747.

About Senetek, PLC

Senetek PLC (OTCBB:SNKTY) is a life sciences company engaged in the development of breakthrough technologies that target the science of healthy aging. The company’s extensive research collaborations have resulted in a strong pipeline of patented compounds and products with broad therapeutic applications and a leading presence in dermatology. Senetek collaborates with established specialty pharmaceutical companies in the final development and marketing of its proprietary products, most recently resulting in the development of kinetin, the best-selling anti-aging product sold in the North American physician market. For more information, visit the company’s website at http://www.senetekplc.com/.

Senetek PLC

CONTACT: company, William O’Kelly of Senetek, PLC, +1-707-226-3900,ext. 102; or media, Michael Rogers, +1-212-255-7210,[email protected], for Senetek PLC

Web site: http://www.senetekplc.com/

SUNNYVALE, Calif., Sept. 4 /PRNewswire/ — Pathwork Diagnostics, a molecular diagnostics company focused on oncology, announced the closing today of a $20 million financing led by Abingworth. The announcement came on the heels of FDA’s clearance for the Pathwork(R) Tissue of Origin Test for diagnosis of tumors of uncertain origin, including poorly differentiated, undifferentiated and metastatic tumors.

“With this $20 million round of financing completed and the recent FDA clearance, the company is well positioned to fund important commercialization programs, including offering the Pathwork Tissue of Origin Test through an additional distribution channel, and building our pipeline,” said Deborah J. Neff, President and Chief Executive Officer of Pathwork Diagnostics.

In addition to offering the Pathwork Tissue of Origin Test as a service through the CLIA-certified Pathwork Diagnostics Laboratory, FDA clearance of the in vitro diagnostic (IVD) kit version of the test will give Pathwork’s customers the opportunity to purchase an IVD kit and run the test in their own labs. “Our channels to market are expanding and we are building our customer support team to provide outstanding service to our customers,” said Neff. “In addition, we are investigating new applications of our technology that will enable us to offer new, breakthrough diagnostic capabilities to the oncology community.”

Pathwork’s lead investor, Abingworth, based in London and with local offices in Menlo Park, Calif., specializes in the life sciences and healthcare industries. “We are delighted to become an investor in this unique company,” said Ken Haas, Venture Partner with Abingworth. “Molecular diagnostics is already making a significant difference in the care of cancer patients and Pathwork, with its combination of a novel and proprietary approach, a validated test available through two commercial channels and a broadly applicable platform, is poised to be a leader in this field.”

Abingworth joins the existing investors participating in this round, including Prospect Venture Partners, Advent Venture Partners, Novus Ventures, Venrock and Versant Ventures. “Completing this successful financing in the current economy, with well-respected investment firms is a strong vote of confidence in our technology and commercialization strategy,” said Neff.

About Pathwork Diagnostics

Pathwork Diagnostics, Inc., based in Sunnyvale, Calif., develops and commercializes high-value molecular diagnostics for oncology. The company delivers FDA-cleared, microarray-based tests to clinical laboratories and also provides diagnostic tests through its CLIA-certified laboratory. The company’s initial tests utilize Pathwork Diagnostics’ proprietary analytics and a companion Pathchip(R) microarray, which runs on the proven Affymetrix GeneChip(R) System. The company’s first test — the Pathwork Tissue of Origin Test — is now FDA-cleared as an in vitro diagnostic kit. A functionally equivalent version of the test is also available through Pathwork(R) Diagnostics Laboratory. The test aids in determining a tumor’s origin so that standard-of-care, cancer-specific treatment can begin. For more information, please call toll-free 1.877.808.0006 or visit http://www.pathworkdx.com/ .

(C) 2008 Pathwork Diagnostics, Inc. All rights reserved. Pathwork, Pathchip, Pathwork Diagnostics, and the Pathwork Diagnostics logo are trademarks or registered trademarks of Pathwork Diagnostics, Inc. Other names may be the trademarks of their respective owners.

Pathwork Diagnostics

CONTACT: Scott Shadiow of Pathwork Diagnostics, +1-415-515-0786,[email protected]

Web site: http://www.pathworkdx.com/

The US Food and Drug Administration, or FDA, has assigned Priority Review to GTC Biotherapeutics, Inc.’s (“GTC”, Nasdaq: GTCB) Biologic License Application, or BLA, for ATryn(R). Priority Review is granted to applications for products that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-threatening disease. Under Priority Review, the FDA’s target date for action on the BLA is February 7, 2009.

“We are pleased that the FDA has recognized the inherent advantage of ATryn(R) as the only recombinant antithrombin product that may become available to patients with hereditary antithrombin deficiency who are at risk of developing serious or potentially life-threatening venous thromboembolic events,” stated Geoffrey F. Cox, PhD, GTC’s Chairman and CEO. “We look forward to continuing our collaborative efforts with the FDA during the review process.”

The FDA’s goal for completing review of applications assigned Priority Review is six months from receipt of the complete application. GTC filed the last section of the BLA on August 7, 2008.

ATryn(R) is GTC’s recombinant form of human antithrombin, a plasma protein with anticoagulant and anti-inflammatory properties. The BLA seeks a license to sell ATryn(R) in the United States for the prophylactic treatment of deep vein thrombosis and other thromboembolisms in patients with hereditary antithrombin deficiency who are undergoing high risk surgical and childbirth procedures. There are no other recombinant forms of antithrombin available to treat this rare patient population. GTC has licensed ATryn(R) to OVATION Pharmaceuticals, Inc. to develop and market it in the United States.

About GTC Biotherapeutics

GTC Biotherapeutics develops, supplies, and commercializes therapeutic proteins produced through transgenic animal technology. In addition to ATryn(R), GTC is developing a portfolio of recombinant human plasma proteins with known therapeutic properties. These proteins include recombinant forms of human coagulation factors VIIa, VIII, and IX, which are used for the treatment of hemophilia, and alpha-1 antitrypsin. GTC also has a monoclonal antibody portfolio that includes a monoclonal antibody to CD20 and a monoclonal antibody to CD137. GTC’s intellectual property includes a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. GTC’s transgenic production platform is particularly well suited to enabling cost effective development of proteins that are difficult to express in traditional recombinant production systems as well as proteins that are required in large volumes. Additional information is available on the GTC web site, http://www.gtc-bio.com.

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the timing of the FDA’s review of the BLA for ATryn(R). Such forward-looking statements are subject to a number of risks, uncertainties and other factors that could cause actual results to differ materially from future results expressed or implied by such statements. Factors that may cause such differences include, but are not limited to, the risks and uncertainties discussed in GTC’s most recent Annual Report on Form 10-K and its other periodic reports filed with the Securities and Exchange Commission, including the uncertainties associated with dependence upon the actions of regulatory agencies. GTC cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this document, and GTC undertakes no obligation to update or revise the statements, except as may be required by law.

Following a rigorous review, Randolph Medical Center, a critical access hospital in Roanoke, Alabama, has selected Dairyland Healthcare Solutions as its technology partner. Together, the two are embarking on what may become a landmark project to set standards and create a model for how non-affiliated hospitals can exchange patient data in full compliance with all patient privacy regulations.

Randolph Medical Center is the only Alabama Hospital to receive funding from the Department of Health and Human Services (HHS) through a $1.2 million Critical Access Hospital Health Information Grant. The data exchange will be operational by February 2009. The Alabama Department of Public Health will administer the grant between Randolph Medical Center, a rural critical access hospital (CAH) and East Alabama Medical Center which is about 50 miles away and is the primary transfer hospital for Randolph. The initiative will be deployed in three phases beginning in October and will enable easy data transfer to East Alabama for telemedicine and clinical studies.

Dairyland was chosen from a large field of technology vendors by a selection committee that included nurses, physicians and other practitioners. They selected the company for two key reasons: the comprehensiveness and ease of use of its technology and Dairyland’s track record in building patient data exchanges. Currently, Dairyland is working with the Louisiana Rural Hospital Coalition to build a data exchange between a group of hospitals and Louisiana State Medical Center at Shreveport. This ambitious initiative–most of the affected hospitals are in communities devastated by Hurricane Katrina–has caught the eye of Alabama’s Department of Public Health and Dairyland has been invited to meet with the department to provide strategic insights on the Louisiana project.

Under The Regulatory Microscope

But the Alabama project charts entirely new territory: it is believed to be one of the first efforts between two non-affiliated hospitals to openly share patient data in real-time. This scenario raises many legal, procedural and potentially ethical issues that must be effectively addressed if America is to realize the vision of totally electronic medical records. Together, Randolph and Dairyland are tackling these often complex issues.

In what may become the framework for how non-affiliated hospitals can navigate complex patient data privacy regulations, Randolph Medical and East Alabama are working through and setting protocols for a range of issues including how patient consent is secured and which medical personnel can view which documents.

Randolph Medical Center CEO Tim Harlin says that the Alabama Department of Public Health is very involved in terms of strategic oversight in these areas. “Hospitals across the country are wrestling with how, where and to whom to provide patient information. We’re very much under the microscope on this initiative,” he explained.

Dairyland CEO James Burgess said that “We are pleased that Randolph Medical Center has chosen Dairyland as its technology partner. We are enthusiastic about helping Randolph work through many of the questions that relate to patient records and establish new technology standards to address these. This is a very important and exciting initiative to be part of,” he said.

Dairyland’s experience in building data exchanges coupled with the thoroughness of its clinical solutions will help facilitate the process of developing protocols in this uncharted territory between hospitals with no formal relationship. Harlin said that Dairyland’s technology consistently scored high on important criteria and the selection committee was impressed with the comprehensive and fully integrated capabilities of Dairyland’s clinical solutions. “We had a $1.2 million gift. We’re a small, rural hospital so freeing up that kind of capital does not happen often. We decided early on that we were not going to take the path of least resistance.”

Alabama Ranks High in Heart Disease: Need for Fast Data on Patients

At Randolph Medical Center, the technology initiative is designed to enable fast, easy access to critical patient information by health providers at both hospitals–especially cardiologists–since Alabama ranks near the top among all states for heart disease and Randolph Medical is located in one of the highest cardiac disease counties in the state. As a small rural hospital, Randolph’s role is to stabilize cardiac cases and then transfer them quickly to East Alabama Medical Center, which is a full service hospital with total cardiac capabilities. The initial goal of the data exchange is for East Alabama cardiologists to have real-time access to lab results for patients who are en route to their Emergency Room.

About Dairyland Healthcare Systems

Dairyland Healthcare Solutions is an award-winning healthcare information systems company that links essential information between small community hospitals and their healthcare delivery and business networks. Dairyland enables its hospital partners to deliver the highest level of patient care by providing the information infrastructure required to operate effectively in the dynamic and complex healthcare delivery environment. For almost three decades, Dairyland has partnered with leading community hospitals to help them improve efficiencies, enhance profitability and ensure patient safety by providing solutions to manage, integrate and access key financial, clinical and patient information. Dairyland is the only company to be awarded three consecutive “Best in KLAS” ratings in the Community Hospital Information Systems category. To learn more, visit: http://www.dhsnet.com.

By Fuentes-Orozco, Clotilde Cervantes-Guevara, Gabino; Mucino- Hernandez, Ivette; Lopez-Ortega, Alejandro; Ambriz-Gonzalez, Gabriela; Gutierrez-de-la-Rosa, Jose Luis; Gomez-Herrera, Efrain; Hermosillo-Sandoval, Jose Manuel; Gonzalez-Ojeda, Alejandro

Background: The effect of parenteral GLN on recovery from severe acute pancreatitis has not been thoroughly investigated. The aims of this study were to determine whether parenteral GLN improves nutrition status and immune function, and to determine its ability to reduce morbidity and mortality in patients with this condition. Methods: In a randomized clinical trial, 44 patients with severe acute pancreatitis were randomly assigned to receive either standard PN (n = 22) or L-alanyl-L-glutamine-supplemented PN (n = 22) after hospital admission. Nitrogen balance, counts of leukocytes, total lymphocytes, and CD4 and CD8 subpopulations, and serum levels of immunoglobulin A, total protein, albumin, C-reactive protein, and serum interleukin (IL)-6 and IL-10 were measured on days 0, 5, and 10. Hospital stay, infectious morbidity, and mortality were also evaluated. Results: Demographics, laboratory characteristics, and pancreatitis etiology and severity at entry to the study were similar between groups. The study group exhibited significant increases in serum IL-10 levels, total lymphocyte and lymphocyte subpopulation counts, and albumin serum levels. Nitrogen balance also improved to positive levels in the study group and remained negative in the control group. Infectious morbidity was more frequent in the control group than in the study group. The duration of hospital stay was similar between groups, as was mortality. Conclusion: The results suggest that treatment of patients with GLN- supplemented PN may decrease infectious morbidity rate compared with those who treated with nonenriched PN. (JPEN J Parenter Enteral Nutr. 2008;32:403-411) Keywords: severe acute pancreatitis; GLN- supplemented PN; infectious morbidity

Glutamine (GLN), which is synthesized in organs such as the skeleton, muscle, lungs, and brain, is the most abundant amino acid in the plasma and intracellular amino acid pools. Although GLN is a nonessential amino acid, it is classified as a conditionally essential amino acid because of increased demand for it in catabolic states.1-3

Support of patients with acute pancreatitis with parenteral nutrition (PN) has been suggested to improve functioning of the gastrointestinal system and the pancreas. Furthermore, long-term ileus and surgical interventions preclude oral and enteral nutrition (EN) of patients with severe acute pancreatitis. It has been suggested that PN may be useful for management of patients with acute pancreatitis by preventing exocrine secretions responsible for autodigestion of the pancreas. PN has also been used to support optimal recovery as well as for life support. 4-6

In recent years, EN has been considered the method of choice for the nutrition of patients with mild acute pancreatitis. However, PN is also useful for patients suffering from mild acute pancreatitis accompanied by nausea and vomiting.7,8 Although most patients develop the mild form of acute pancreatitis, 20% develop the severe or life-threatening form, which is characterized by local complications such as necrosis, infection, abscesses, pseudocysts, acute respiratory and renal failure, as well as an intense systemic inflammatory response accompanied by a high risk of multiple organ failure.9 Severe acute pancreatitis, like sepsis and trauma, is characterized by a marked degree of protein breakdown.10-14 Catabolism of body protein may be as high as 2% per day.15 A study using the Harris-Benedict equation to predict resting energy expenditure showed that patients with acute pancreatitis have markedly elevated metabolic rates (77%- 139% of predicted energy expenditure), especially in the presence of septic complications, which are commonly observed in acute pancreatitis.16 In patients with nausea, vomiting, and intermittent ileus secondary to intraabdominal infection or repetitive surgical debridement of necrotic and infected pancreatic and peripancreatic tissue, nutrient requirements cannot be met by EN.17

Although PN contributes to optimal recovery and pancreas function, a long period of PN (>10 days) increases the risk of an acute inflammatory response and septicemia.18,19 It has been postulated that GLN is an immunomodulatory agent, as it has beneficial effects on the cells of the immune system and their functions.20,21 Previous studies have shown that GLN-enriched PN formulas improve the prognosis of septic and surgical patients22-25 by decreasing the acute inflammatory response commonly observed in such patients.3

This study was performed to determine the effects of early administration (within the first 48 hours of the onset of severe acute pancreatitis) of GLN dipeptide-supplemented PN on the nutrition status, inflammatory response, occurrence of complications, duration of hospital stay, and mortality of patients with severe acute pancreatitis.

Patients and Methods

Patients and Study Design

The experiment was designed as a randomized, doubleblind, controlled clinical trial. The study period was from April 2003 to October 2005. Patients with suspected episodes of acute pancreatitis were studied to confirm the diagnosis. Acute pancreatitis was defined as an increase in serum amylase concentrations to a level 3- fold greater than basal levels, or abdominal pain and findings typical of acute pancreatitis upon abdominal ultrasound or computed tomography (CT). The severity of acute pancreatitis was defined using the following criteria26-28: an Acute Physiology and Chronic Health Evaluation (APACHE) II score >8, a Ranson score >4 at 48 hours, a C-reactive protein (CRP) serum level >1 50 mg/L, and CT with at least a Balthazar’s CT grade of C, D, or E at admission and a CT severity index (CT grade plus necrosis score) >/= 4.

Patients were admitted to the intensive care unit (ICU) where a subclavian central venous catheter was collocated in all cases. Intensive monitoring was performed and IV liquids were administered according to the hemodynamic state of the individual. Patients with renal failure (creatinine > 1 80 mol/L) or hepatic failure (bilirubin > 40 mol/L, alanine aminotransferase [ALT] > 100 U/L and aspartate aminotransferase [AST] > 100 U/L) were excluded from the study. Patients with severe neutropenia (

Patients satisfying the enrollment criteria received a serial number allocated in ascending order of enrollment. Based on this number, the patients were assigned to one of the study groups. The patient number appeared on the patient’s prescription and was used to prepare the all-inone bag for the patient. The blinded preparation of solutions was conducted with the help of the pharmacy. All investigators involved in the analysis, patients, and relatives of patients were blinded to the randomization until the 10- day follow-up had been completed for all subjects. Patients were randomly assigned to receive either standard PN (n = 22) or GLN- supplemented PN (n = 22), which commenced between 24 and 48 hours after admittance to the ICU. Baseline hematology and biochemistry were conducted at enrollment and on protocol days 5 and 10. Routine hematology consisted of measurement of hemoglobin levels, white blood cell counts, platelet counts, and differential with blood cell (neutrophils and lymphocytes) counts. Routine biochemistry consisted of measurements of levels of sodium, potassium, chloride, AST, ALT, glucose, cholesterol, urea, creatinine, total bilirubin, triglycerides, and bicarbonate.

Feeding Regimen

The 2 PN formulas were isonitrogenous and isocaloric. The control group received standard PN, which supplied 30 kcal/kg per day. The nonprotein calories were derived from carbohydrates (50% hypertonic glucose) and lipids (20% fatty acids) in a ratio of 60:40. The protein calories were derived from amino acids (8.5%; 1.5 g/kg per day). The treatment group was given 0.40 g/kg per day of L-alanyl-L- Glutamine (Dipeptiven, Fresenius Kabi, Bad Homburg, Germany) plus 8.5% standard amino acids (1.1 g/kg per day). For caloric estimations, adjusted body weight was considered in each patient (adjusted body weight = 0.25 x [actual body weight – ideal body weight] + ideal body weight). Nutrition support was initially infused at 80% of the calculated en ergy requirements, then increased over 48 h to achieve 100% of the target energy rate and continued until death or as long as clinically required (normal diet or full EN). The clinicians were allowed to adjust the total volume of PN delivered and the amount of water and electrolytes administered on a daily basis as judged clinically appropriate. All patients were under close metabolic control mediated by the infusion of IV crystalline insulin according to serum or capillary glucose levels. Nitrogen Balance

A fluid balance chart was maintained during the study period. Total urinary nitrogen was determined using the micro-Kjeldahl method.29 The amount of nitrogen administered via PN was determined by multiplying the volume of PN administered by the nitrogen concentration of the infusate. Insensible nitrogen losses were assumed to be 0.025 g/kg per day. Nitrogen balance was calculated from the formula: daily nitrogen balance = nitrogen administered – total urinary nitrogen loss – insensible nitrogen loss. For those patients treated surgically during the follow up period, drainage losses were taken into account when estimating nitrogen balance. For each 1000 mL/24 hours of fluid drained from open abdomen or close drains, 1 g of nitrogen was empirically added to the feeding formula. Blood and plasma transfusions were not considered.30

Endpoint Definitions

The primary efficacy variables were infectious morbidity, nitrogen balance, leukocyte, counts of leucocytes, lymphocytes and CD4 and CD8 subpopulation, and levels of immunoglobulin A (IgA), total protein, albumin, CRP, interleukin (IL)-6, and IL-10. Systemic inflammatory response syndrome, sepsis, septic shock, and multiple organ failure syndrome were defined as follows:

* Systemic inflammatory response syndrome was defined as a systemic inflammatory response to a variety of severe clinical insults manifested by at least 2 of the following conditions: (1) temperature > 38[degrees]C or

* Sepsis was defined as the systemic response to infection. Such a response is manifested by at least 2 of the following conditions as a result of infection: (1) temperature higher than 38[degrees]C or lower than 36[degrees]C; (2) heart rate faster than 90 beats/ min; (3) respiratory rate faster than 20 breaths/min or an arterial partial pressure of carbon dioxide below 4.3 kPa; and (4) white blood cell count larger than 12,000 cells/mm^sup 3^, less than 4000 cells/mm^sup 3^, or more than 1 0% of immature forms.

* Septic shock was defined as sepsis with hypotension despite adequate fluid resuscitation and the presence of perfusion abnormalities, including but not limited to lactic acidosis, oliguria, or an acute alteration in mental status. Patients on inotropic or vasopressor agents could not be hypotensive at the time that perfusion abnormalities were measured.

* Multiple organ dysfunction syndrome was defined as the presence of altered organ function in an acutely ill patient such that homeostasis could not be maintained without intervention.

Infectious morbidity included intraabdominal and extra-abdominal infections.

* Diagnosis of infected pancreatic necrosis, pancreatic abscess, or generalized peritoneal infection was based on microbiological examination (gram stain and culture for aerobic and anaerobic germs and fungi) of samples obtained by CT-guided fineneedle aspiration of pancreatic, peripancreatic, or any intra-abdominal collection and confirmed in fluid or tissue specimens obtained during surgery.

* Pneumonia was defined as a chest radiographic examination showing new or progressive infiltrate, consolidation, and cavitation (interpreted by a radiologist blinded to a patient’s treatment assignment), and at least 2 of the following: (1) temperature above 38.5[degrees]C or below 35[degrees]C, (2) a white blood cell count larger than 10 x 107L or less than 3 x 109/L, and (3) isolation of pathogens from the sputum, bronchial aspirates or bronchial brushing.

* Bacteremia was diagnosed when a pathogen was isolated from the blood with a temperature above 38.5[degrees]C or below 35[degrees]C or a white blood cell count larger than 10 x 10^sup 9^/L or less than 3 x 10^sup 9^/L, and it was not related to infection at another site.

* Urinary tract infection was defined as the isolation of at least 10^sup 5^ colonies/mL of a pathogen from the urine.

* Catheter-related sepsis was diagnosed if the patient had local signs of infection at the entry site, a temperature > 38.5[degrees]C or 10 x 109/L or

Secondary efficacy parameters included durations of hospital stay, ICU stay, ventilatory support, and the incidence of mortality.

Ethical Aspects

This study was conducted according to the principles of the Declaration of Helsinki of 1989 and the Mexican Health Guidelines. The Ethical Committee of the Western Medical Center of the Mexican Institute of Social Security approved all protocols. Full, written informed consent was obtained from all patients before their inclusion in the study.

Statistical Analysis

All quantitative values in the text refer to the mean +- standard deviation (SD). Comparison between means was assessed using ANOVA or the unpaired Student’s t test. When data were not distributed normally, comparisons were made using the Mann-Whitney U test. Qualitative values are expressed as proportions. Comparison between proportions was assessed using the chi^sup 2^ test or Fisher’s exact test. The analysis was performed using SPSS release 10.0 for Windows (SPSS Inc., Chicago, IL). A P value of

Results

Demographic and laboratory characteristics of the control (n = 22) and study (n = 22) groups were similar at entry (Table 1 ). All 44 patients had severe acute pancreatitis. The randomization process resulted in groups with similar patient characteristics. Sex distribution and body mass index (BMI) were similar between groups. The most common type of pancreatitis was biliary pancreatitis, and the second most common was alcoholic pancreatitis. The APACHE II scores of the groups were similar at the beginning of the study. The CT severity index was also similar between groups. As established by the inclusion criteria, patients presented with at least 30% necrosis of the pancreatic gland as evaluated by contrast-enhanced CT scanning.

Table 1 . Baseline Characteristics of the Patients in the Study (GLN+) and Control Group (GLN-) (mean +- SD)

Nutrient Intake

Target energy requirements were reached in the first 48 hours. Patients of the control group received initially from 1765 +- 124.97 to 2020.68 +- 207.0 calories/day in the subsequent days, and patients of the study group received 1798 +- 156.25 to 2024.81 +- 174.70 calories each day. There was no difference between the amount of initial and targeted calories requirements between groups (P = .44 and P = .99, respectively).

Patients of the control group received 105.6 +- 20.35 g of proteins/day and 16.9 +- 3.2 g of nitrogen/day, and patients of the study group received 107.9 +- 14.07 g of proteins/day and 17.2 +- 2.23 g of nitrogen/day. There was no difference in the amount of proteins and nitrogen administered in both groups (P = .66 and P = .65, respectively).

Proteins, Albumin, and Nitrogen Balance

Protein and albumin levels as well as nitrogen balance are depicted in Table 2. Protein levels increased in both groups in a similar fashion, but the increase was only significant on day 10 in favor of the study group. Albumin levels also rose in a similar fashion in both groups but serum levels remained below 3 g/dL limits. On protocol day 10, the difference between groups was significant (P = .01). During follow-up, nitrogen balance remained negative in the control group (Table 2). The patients in the study group attained a slightly positive nitrogen balance on day 10 and the difference was significant (P = .049).

Table 2. Laboratory Findings at Different Time Intervals (mean +- SD)

Total Leukocyte Counts

During follow-up, patients of the study and control group shown elevated leukocyte counts (Table 2). Basal values were not different between groups, nor were counts on day 5; on day 10, the leukocyte count of the study group was less than that of the control group (P = .04).

Total Lymphocyte Counts

Total lymphocyte counts are depicted in Table 2. Patients of the study group experienced progressive elevations of total lymphocyte counts in opposition to the control group, and the difference was not significant on days 0 and 5. At the end of the follow-up period, the total lymphocyte count was higher in the study group. The difference was significant (P = .04).

CD4 and CD 8 counts

Counts of CD4 and CD8 lymphocyte subpopulations are depicted in Table 2. Both CD4 and CD8 levels increased with time for the L- alanyl-L-glutamine- supplemented PN group relative to those of the standard PN group, and the difference was statistically significant on days 5 and 10 for CD4 count (P = .003 and P = .03, respectively) and only on day 10 for CD8 count (P = .03).

Immunoglobulin A

Average IgA levels are shown in Table 2. Patients in the study and control groups experienced a progressive elevation in IgA serum levels, but differences on days 0 and 5 were not statistically significant. In contrast, IgA serum levels on day 10 were higher in patients of the study group. This difference was significant (P – .01).

IL and CRP Levels

IL-6, IL-10, and CRP levels are depicted in Table 2. IL-6 levels decreased on day 10 in study group patients. In the control group, levels remained elevated during the followup period. The difference was statistically significant at this point (P = .03). Regarding the anti-inflammatory IL10, patients of both groups showed progressive increasing levels, but the levels were higher in the study group than in the control group on day 10 (P = .02). With reference to CRP levels, we observed a progressive reduction in both groups, but it was notably different in patients of the study group on day 10 (P = .005). Infection Rate

The number of patients with infectious morbidity was significantly different between groups. In the control group, 16 patients suffered from at least 1 infective complication, in contrast to the study group in which only 9 patients developed at least 1 infective episode (72.7% vs 40.9%, P = .03). The total number of infectious episodes is shown in Table 3.

Table 3. Infectious Complications

Table 4. Surgical Interventions

Surgical Interventions

Surgical interventions are shown in Table 4. Almost all patients with biliary pancreatitis underwent open or laparoscopic cholecystectomy during hospitalization, usually during the third or fourth week of hospital stay (21 +- 4 days). Patients with intra- abdominal septic complications were treated between the second and third week after admission (14 +- 2 days). All patients with infected necrosis required repetitive open drainage. Patients with suspected generalized intra-abdominal infection underwent laparotomy and drainage of the abdominal cavity until absolute control of the infection was attained; this required 2.3 +- 0.57 and 3.1 +- 0.47 reinterventions in the study and control groups, respectively. More reinterventions were required to treat intra-abdominal infection in the control group (P = .03).

Secondary Efficacy Parameters

There were no between-group differences in the duration of stay in the ICU or the duration of ventilatory support (Table 5). All patients required > 10 days of PN before oral or EN was commenced. Mortality was 22.7% in the control group and 9% in the study group (P = .20). To establish the clinical relevance of mortality, we calculated absolute risk reduction, 13.7%; relative risk reduction, 60%, and number needed to treat to prevent 1 death, 8 patients. In all fatal cases, the cause of death was multiple organ failure.

Table 5. Secondary Efficacy Parameters (mean +- SD)

Discussion

GLN is the most abundant amino acid in the body. Plasma levels decrease during critical illness, suggesting that GLN becomes limited.32 Parenteral GLN supplementation improves nitrogen balance.33,34 GLN is involved in interorgan nitrogen transport, functions as a nitrogen donor for nucleotides and amino sugars, and is a key substrate for renal ammonia formation.35 As the preferred fuel of enterocytes, GLN may reduce bacterial translocation across the gut wall and thus reduce the risk of sepsis.32,36 Cells of the immune system also use GLN as fuel and the amino acid contributes to antioxidant defense37 through the production of glutathione.32 GLN enhances the expression of heat shock proteins, which are important for protection against tissue damage during stress or injury.38,40

Patients with mild acute pancreatitis can begin oral feeding after 5-7 days of medical treatment with IV solutions, analgesics, and gastric drainage if necessary. For this group of patients, nutrition support with either EN or PN is considered unnecessary. However, several studies and guidelines have emphasized the superiority of EN over PN.8,41-43 Fortunately, most patients with acute pancreatitis will not develop the severe form of pancreatitis. Those who develop severe acute pancreatitis suffer intense catabolic stress with abdominal manifestations of compartmental syndrome and ileus, which precludes the use of the enteral route, at least during the first 10 days after the beginning of the catabolic state. PN is still an option for these patients if they cannot be fed orally or enterally.44-47

In the past 10 years, 6 studies that evaluated PN with or without supplemental parenteral GLN have been published.48-53 A study by Zhao et al48 compared a treatment group receiving PN with added parenteral GLN (0.22 g/kg per day) with a control group receiving conventional PN without GLN. The treatment group was transitioned to receive supplemental EN once gut paralysis was relieved. Inflammatory markers decreased faster and to a greater extent in the treatment group compared with controls at day 4, 7, and 11 as well as APACHE II score and basal Balthazar’s severity index. Unfortunately, no outcome parameters were evaluated in the 96 patients randomized in this study.

In a second study, De Beaux et al49 evaluated PN with and without supplemental parenteral GLN (0.22 g/kg per day). However, only patients receiving long-term PN who had persistent failure of the GI tract for more than 7 days after the onset of acute pancreatitis were included in the study. As a result, patients were randomized at 10-18 days after the onset of the illness. The severity of the episodes of acute pancreatitis was not described. The incidence of major pancreatic complications was observed in more than 50% of the patients of both groups. Levels of IL-8, an inflammatory cytokine released by mononuclear cells, decreased in the GLN group, whereas levels increased significantly in controls receiving PN alone (P = .045). There were no deaths in the study.

Ockenga et al50 performed a study of patients with mild to moderate pancreatitis randomly assigned to isocaloric and isonitrogenous PN with 0.3 g of L-alanyl-L-glutamine and 1.2 g/kg per day of standard amino acids vs 1.5 g/kg per day of standard amino acids in the control group. The study examined 28 patients (n = 14 in each group) with an APACHE II score of 5.7 and 5.1 and a Balthazar’s severity index of 1.9 and 2.4, respectively. They found that patients in the treatment group reduced mean hospital stay compared with controls receiving PN without supplementation and experienced significantly shorter duration of nutrition therapy. Visceral protein levels, including those of albumin, transferrin, and total protein were all significantly greater in the GLN supplementation group (P

Xian-Li et al51 studied 64 patients with severe acute pancreatitis randomized to receive traditional conservative therapy (group I, n = 23). For these patients, glucose was the major source of energy. Combined with traditional conservative therapy, 21 patients in group II and 20 cases in group III were treated by isocaloric and isonitrogenous PN and, in group III, with additional GLN dipeptide-supplementation (0.4 g/kg per day of alanyl- glutamine). PN with GLN was associated with significantly less pancreatic infection (0% vs 23.8%), fewer overall complications (20% vs 52.4%), and less mortality (0% vs 14.3%) compared with PN without supplemental GLN.51

In a recent publication by Sahin et al,52 a total of 40 patients with acute pancreatitis who had Ranson’s score between 2 and 4 were randomly assigned to receive GLN (0.3 g/kg per day) and standard amino acids (1.1 g/kg per day); the control group received 1.4 g/kg per day of standard amino acids. The lengths of PN use and hospital stays were not different between groups. The complication rates in the treatment and control groups were 10% and 40%, respectively. Mortality was 10% in the study group and 30% in the control group.52

Finally, Xue et al53 evaluated the therapeutic effect of alanyl- glutamine dipeptide (AGD) in a randomized clinical trial of 76 patients with severe acute pancreatitis in early and advance stages. Patients of the early treatment group received 100 mL/day of 20% AGD intravenously for 10 days started either on admission day or 5 days after (late treatment group) admission. The severity of the episodes were evaluated with 48-hour Ranson score (4.5 +- 1.7 vs 4.8 +- 1.6), 24-hour APACHE II score (10.8 +- 3.5 vs 10.2 +- 3.1) and CT score (5.8 +- 2.3 and 5.9 +- 2.4). As primary endpoints, the authors studied the presence and duration of organ failure. They demonstrated a significant reduction in the length of organ failure. The incidence of infection was 7.9% in the early treatment group, 5 patients required surgical interventions (13.2%), and mortality was 5.3%. In the late group, infection was observed in 26.3% of the cases, 13 required surgical interventions (34.2%), and mortality was 21.1%. The authors concluded that early treatment with AGD achieved a better clinical outcome in severe acute pancreatitis patients.53

In our study, we included patients with severe acute pancreatitis with a minimum CT severity index of 4 points. All patients developed pancreatic gland necrosis of at least 30%. Patients of the study group received 0.4 g/kg per day of L-alanyl-L-glutamine and patients of the control group received 1.5 g/kg per day of standard amino acids. The primary efficacy parameters were better in patients of the study group. We attribute our results to a reduction in the acute inflammatory response mediated by a decrease in levels of pro- inflammatory IL-6 and CRP and a progressive increase in the level of anti-inflammatory IL-10. We also observed an enhancement of immune function, as the counts of CD4 and CD8 lymphocytes and serum levels of IgA increased to a significantly greater extent in the GLN group than in the control group. In the control group, a slight increase in these parameters was also observed. The study group patients experienced rapid nutritional recovery, as evidenced by high levels of total protein and serum albumin and a slightly positive nitrogen balance on day 10. Probably it was the result ol a modulation of the inflammatory response, as well as a marked reduction in the incidence of septic intra-abdominal and extra-abdominal complications observed in the treatment group. However, albumin levels in study group patients remained below the lower normal limit, probably as a consequence of the intense catabolic state imposed by the severity of the acute pancreatitis.9,10,14 In agreement with the results of studies published by De Beaux et al,49 Ockenga et al,50 Xian-Li et al,51 Sahin et al,52 and Xue et al,53 our results indicate that overall complications, including infectious morbidity, were less frequent in patients receiving GLN- enriched PN. In our study, however, this reduction in infectious complications did not result in a reduction in mortality, duration of ICU stay, or duration of hospital stay. These may be real phenomena or may merely reflect the small sample number of this trial. A clinical trial with a large sample is necessary to resolve this.

Conclusion

Our results suggest that parenteral GLN dipeptide supplementation decreases the incidence of infectious complications. Mortality was not different between groups, but we observed a slight reduction in this secondary efficacy parameter in patients of the study group.

Acknowledgement

The authors would like to thank Rafael Montufa, MD, from Fresenius Kabi, Zapopan, Jalisco, Mexico for his technical support and for finishing this project.

References

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33. Sthele P, Zander J, Mertes N, et al. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet. 1989;1:231-233.

34. Jian ZM, Cao JD, Zhu XG, et al. The impact of alanil- glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: a randomized, double-blind, controlled study of 120 patients. JPEN J Parenter Enteral Nutr. 1999;23:S62-S66.

35. Avenell A. Glutamine in critical care: current evidence from systematic reviews. Proc Nutr Soc. 2006;65:236-241.

36. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005;33:1125-1135.

37. Eaton S. The biochemical basis of antioxidant therapy in critical illness. Proc Nutr Soc. 2006;65:242-249.

38. Singleton KD, Serkova N, Beckey VE, Wischmeyer PE. Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression. Crit Care Med. 2005;33: 1206- 1213.

39. Ziegler TR, Ogden LG, Singleton KD, et al. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med. 2005;31:1079-1086.

40. Wischmeyer PE. Glutamine: the first clinically relevant pharmacological regulator of heat shock protein expression? Curr Opin Clin Nutr Metab Care. 2006;9:201-206.

41. McClave SA, Greene LM, Snider HL, et al. Comparison of the safety of early enteral vs PN in mild acute pancreatitis. JPEN J Parenter Enteral Nutr. 1997;21:14-20.

42. Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004; 328:1407-1409.

43. McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr. 2006;30:143-156.

44. Lobo DN, Memon MA, Allison SP, Rowlands BJ. Evolution of nutritional support in acute pancreatitis. Br J Surg. 2000;87:695- 707.

45. Dejong CH, Greve JW, Soeters PB. Nutrition in patients with acute pancreatitis. Curr Opin Crit Care. 2001;7:251-256.

46. Jeejeebhoy KN. Total parenteral nutrition: potion or poison? Am J Clin Nutr. 2001;74:160-163.

47. McClave SA, Dryden GW. Issues of nutritional support for the patient with acute pancreatitis. Semin Gastrointest Dis. 2002;13:154- 160.

48. Zhao G, Wang CY, Wang F, Xiong JX. Clinical study on nutrition support in patients with severe acute pancreatitis. World J Gastroenterol. 2003;9:2105-2108.

49. De Beaux AC, O’Riordain MG, Ross JA, Jodozi L, Carter DC, Fearon KC. Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell interleukin-8 release in severe acute pancreatitis. Nutrition. 1998;14:261-265.

50. Ockenga J, Borchert K, Rifai K, Manns MP, Bischoff SC. Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis. Clin Nutr. 2002;21:409-416.

51. Xian-Li H, Qing-Jiu M, Jian-Guo L, Yan-Kui C, Xi-Lin D. Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP). Clin Nutr Suppl. 2004;1:43-47.

52. Sahin H, Mercanligil SM, Inanc N, Ok E. Effects of glutamine- enriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr. 2007;61:1429-1434.

53. Xue P, Deng LH, Xia Q, et al. Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage. World J Gastroenterol. 2008;14:474-478.

Clotilde Fuentes-Orozco, MD, PhD1; Gabino Cervantes-Guevara, MD, MSc2; Ivette Mucino-Hernandez, MD1; Alejandro Lopez-Ortega, MD1; Gabriela Ambriz-Gonzalez, MD, MSc1; Jose Luis Gutierrez-de-la-Rosa, MD3; Efrain Gomez-Herrera, MD3; Jose Manuel Hermosillo-Sandoval, MD3; and Alejandro Gonzalez-Ojeda, MD, PhD, FACS1 Financial disclosure: none declared.

From the 1 Medical Research Unit in Clinical Epidemiology, Western Medical Center, Mexican Institute of Social Security; 2 Department of Nutritional Support at Civil Hospital “Fray Antonio Alcalde,” University of Guadalajara; and 3 Department of General Surgery and Nutritional Support, Specialties Hospital at Western Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.

Received for publication April 25, 2007; accepted for publication March 10, 2008.

Address correspondence to: Alejandro Gonzalez-Ojeda, MD, Calle Jose Enrique Rodo # 2558, Colonia Prados Providencia, 44657, Guadalajara, Jalisco, Mexico; e-mail: [email protected].

Copyright American Society for Parenteral and Enteral Nutrition Jul/ Aug 2008

(c) 2008 JPEN, Journal of Parenteral and Enteral Nutrition. Provided by ProQuest LLC. All rights Reserved.

SHOP assistant Emma Hutchinson is preparing to do the Great North Run in memory of her cousin, who died this year at the age of 16.

The 18-year-old hopes to raise money to fight cystic fibrosis (CF), the disease which claimed the life of her cousin, Rebecca Cork, of River Garth, Darlington.

Miss Hutchinson, who has never taken part in any long distance event before, is building up her fitness with regular training runs from her home at Manor Cottage, in Winston, near Barnard Castle.

She has already collected more than [pounds]300 in sponsorship from friends and relatives ahead of the 13.1-mile race on Sunday, October 5.

She said: ?I was very sad about losing Rebecca, and I want to do all I can to help others who suffer from this awful illness.

?I aim to raise as much money asI can to fund research into it, so that other young people with CF can look forward to a brighter future. ? Anyone wishing to sponsor Miss Hutchinson can get in touch by logging onto justgiving. com/emma hutchinsonruns She has been training with her friend Joanne Slater, 18, of Barnard Castle, who is doing the run to raise funds for bowel cancer research.

(c) 2008 Northern Echo. Provided by ProQuest LLC. All rights Reserved.

QUEBEC CITY, Sept. 4 /PRNewswire-FirstCall/ — The Previstage(TM) GCC Colorectal Cancer Staging Test, recently launched by DiagnoCure Oncology Laboratories, a wholly owned subsidiary of DiagnoCure Inc., is featured in this month’s issue of Expert Reviews in Molecular Diagnostics. The article, which was written by Dr. Scott A. Waldman and Dr. Alex Mejia, from Thomas Jefferson University, reports that Previstage(TM) GCC detects occult metastases in lymph nodes, identifying patients who may be at increased risk of developing recurrent disease and who could most benefit from adjuvant chemotherapy.

The article discussed the limitations of the traditional microscopic method for the staging of colorectal cancer patients, and the benefit of molecular techniques, such as the GCC marker and the Previstage(TM) GCC Colorectal Cancer Staging Test. In particular, the article reported that eleven published studies suggested that other markers, such as CEA and CK, were not useful for colorectal cancer patient management. In comparison, recent studies demonstrated that guanylyl cyclase C (GCC) was a specific marker for metastatic colorectal cancer. An initial GCC assay showed an analytical sensitivity of 93% and specificity of 97% in a study in which it identified occult metastases in 6 patients out of 23 (26%), who were considered metastasis-free (stage I and II) by the present microscopic staging method. A more recent prospective, multicenter clinical trial of the GCC assay, which involved 2500 lymph nodes from approximately 250 stage I and II patients, concluded that when the GCC assay was negative, patients had a three to four-fold lower disease recurrence rate. On the other hand, when the GCC assay was positive, patients had a recurrence rate similar to stage III patients. In addition, GCC was the single most important independent prognostic marker for recurrence of stage I and II patients.

“Guanylyl Cyclase C is the most sensitive and specific marker described to date for identifying metastatic colorectal cancer cells in extra-intestinal tissues,” commented Dr. Waldman. “GCC could help identify patients with low risk of disease recurrence and those who might benefit from adjuvant chemotherapy.”

Following on the work of Dr. Waldman, DiagnoCure developed the Previstage(TM) GCC Colorectal Cancer Staging Test at its U.S. CLIA-approved clinical laboratory. The GCC test was optimized to improve the processing of lymph node specimens and the test has shown very high analytical accuracy in detecting GCC levels consistent with the presence of occult metastases in the lymph nodes.

“Dr. Waldman’s studies support the value of Previstage(TM) GCC, developed by DiagnoCure. We believe the test represents a leap forward for the staging of colorectal cancer patients and will help guide clinicians and physicians in making critical treatment decisions,” stated John C. Schafer, President and CEO of DiagnoCure Inc.

About Previstage(TM) GCC

Every year in North America, 174,000 people are diagnosed with colorectal cancer, and 142,000 colorectal cancer surgeries are performed. Staging a patient with colorectal cancer is crucial because it determines the patient’s course of treatment after the surgery. Current standard of care requires that pathologists microscopically examine a thin slice of tissue from each of the lymph nodes harvested during the patient’s surgery to see if cancer has spread. Currently, up to 25 – 30 percent of patients with no pathologically-positive lymph nodes (stage I and II cancers) later develop recurrent disease, presumably through occult metastases that have escaped detection. Most of these patients do not receive additional therapies such as chemotherapy. With a detection capacity that is close to 100,000 more sensitive than microscopic methods, Previstage(TM) GCC provides clinicians with significantly more accurate information for staging a patient with colorectal cancer that will increase their confidence in making critical treatment decisions.

Clinical study data supports the potential for the GCC test to improve the current staging of colorectal patients. The National Cancer Institute sponsored a five-year prospective clinical trial of GCC testing in colorectal cancer patients. This study has been recently completed and the Company’s collaborators at Thomas Jefferson University are presenting the results at major medical conferences throughout the year.

The Previstage(TM) GCC Colorectal Cancer Staging Test is a laboratory-developed test and its performance characteristics have been determined by DiagnoCure Oncology Laboratories.

About DiagnoCure

DiagnoCure (TSX: CUR) is a life sciences company commercializing high-value cancer diagnostic tests and delivering laboratory services that increase clinician and patient confidence in making critical treatment decisions. DiagnoCure Oncology Laboratories, a subsidiary of DiagnoCure Inc., recently launched the Previstage(TM) GCC Colorectal Cancer Staging Test, the first GCC-based molecular test for the management of colorectal cancer. The Company also has a strategic alliance with Gen-Probe for the development and commercialization of a second-generation prostate cancer test using PCA3, DiagnoCure’s proprietary molecular marker. This test is also available through laboratories in the U.S. using PCA3 analyte specific reagents (ASR) from Gen-Probe, in Europe as the CE-marked PROGENSA(TM) PCA3 in vitro assay, and in Canada. In addition to its own research, the Company intends to acquire or in-license additional promising cancer biomarkers from both academic and commercial institutions. For more information, visit http://www.diagnocure.com/.

Forward-looking statements

This release contains forward-looking statements that involve known and unknown risks, uncertainties and assumptions that may cause actual results to differ materially from those expected. By their very nature, forward-looking statements are based on expectations and hypotheses and also involve risks and uncertainties, known and unknown, many of which are beyond DiagnoCure’s control. As a result, investors are cautioned not to place undue reliance on these forward-looking statements. The forward-looking statements regarding the outcome of research and development projects, clinical studies and future revenues are based on management expectations. In addition, the reader is referred to the applicable general risks and uncertainties described in DiagnoCure’s most recent Annual Information Form under the heading “Risk Factors”. DiagnoCure undertakes no obligation to publicly update or revise any forward-looking statements contained herein.

DIAGNOCURE INC.

CONTACT: Investors: J.F. Bureau, CFA Sr. Vice President and CFO,DiagnoCure Inc., (418) 527-6100, [email protected]; Media: U.S.:Troy Pearson, Mentus Life Science, (858) 455-5500 X320, [email protected];Canada: Jean-Pierre Trudel, Jean-Pierre Trudel & Associates, (514) 347-6111,[email protected]; Clinicians: DiagnoCure Oncology Laboratories, CustomerCare 1(877) 701-9007, [email protected]

London, UK: 04 September 2008 – Cancer drug developer Antisoma plc (LSE: ASM; USOTC: ATSMY) today announced that it has started a phase II study of AS1411 in metastatic renal cell carcinoma (kidney cancer).

The single-arm trial will enrol around 30 patients intolerant to, or having relapsed after, previous treatments including a tyrosine kinase inhibitor (sunitinib or sorafenib). It will evaluate the safety and efficacy of AS1411 monotherapy given at 40 mg/kg/day for four days every 28 days for up to two cycles. Efficacy measures in the trial include response rate, time to progression and progression-free survival. Final results are expected in 2010.

Dr Jonathan Rosenberg of the Dana-Farber/Harvard Cancer Center, Boston, MA, an investigator in the trial, said: “AS1411 showed an excellent safety profile and promising signs of activity in renal cell carcinoma patients in phase I testing, and so we’re delighted to be involved in further evaluating its potential in this setting. While a number of new therapies are now available, advanced kidney cancer remains an incurable illness in the large majority of patients, and there is still a clear unmet need to improve treatments available to these patients.”

The phase I trial of AS1411 included 12 patients with renal cell carcinoma. Eleven showed at least stabilisation of their disease. Of these, two had objective responses, including one complete response. A phase II trial of AS1411 in acute myeloid leukaemia was initiated last year and recently reported promising preliminary findings.

Antisoma’s Chief Executive Officer, Glyn Edwards, commented: “Evidence to date suggests that AS1411 has broad potential against blood cancers and solid tumours. With phase II trials now ongoing in both acute myeloid leukaemia and kidney cancer, we are testing AS1411 in diverse settings, and look forward to the roll-out of clinical data over the next two years.”

 Enquiries: Glyn Edwards, CEO Daniel Elger, Director of Communications Antisoma plc +44 (0)20 3249 2100 Mark Court/Lisa Baderoon/Rebecca Skye Dietrich Buchanan Communications +44 (0)20 7466 5000 Brian Korb The Trout Group +1 646 378 2923 

Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the company’s clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management’s current expectations, but actual results may differ materially.

Notes for Editors:

Background on the AS1411 phase II trial in kidney cancer

Additional details of the phase II trial of AS1411 will be available shortly at www.clinicaltrials.gov.

Background on AS1411

Aptamers are short pieces of DNA or RNA that can fold into stable, three-dimensional structures capable of interacting with particular target proteins. AS1411 is the first aptamer to be tested as a treatment for cancer. It binds to the protein nucleolin, which is found on the surface of cancer cells. It is then internalised and has been shown to kill cancer cells from a variety of cell lines. The drug has also shown anti-cancer effects in animal models and promising signs of anti-cancer activity in the clinic. AS1411 was originally developed by Dr Paula Bates, Dr John Trent and Prof. Donald Miller at the University of Alabama and then at the University of Louisville. Antisoma added AS1411 to its pipeline when it acquired the Louisville-based company Aptamera Inc. in February 2005. AS1411 is now in phase II clinical trials in acute myeloid leukaemia (AML) and renal cell carcinoma (RCC).

Background on Antisoma

Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel products for the treatment of cancer. The Company has operations in the UK and the US. Please visit www.antisoma.com for further information about Antisoma.

—END OF MESSAGE—

Copyright Copyright Hugin AS 2008. All rights reserved.

SOURCE: Antisoma plc

By Atalay, Betul Gulsen Yagmur, Cahide; Nursal, Tarik Zafer; Atalay, Hakan; Noyan, Turgut

The objective of this study is to examine the prevalence of malnutrition and evaluate the nutrition status and clinical outcome in hospitalized patients aged 65 years and older receiving enteral- parenteral nutrition. This retrospective study was carried out at Baskent University Hospital, Adana, Turkey. A total of 119 patients older than 65 years were recruited. Patients were classified into 3 groups: protein-energy malnutrition (PEM), moderate PEM, and well nourished according to subjective global assessment (SGA) at admission. All patients were fed by enteral or parenteral route. Acute physiological and chronic health evaluation (APACHE-2) and simplified acute physiology (SAPS 2) scores were recorded in patients followed in the intensive care unit (ICU). Nutrition status was assessed with biochemical (serum albumin, serum prealbumin) parameters. These results were compared with mortality rate and length of hospital stay (LOS). The subjects’ mean (+-SD) age was 73.1+-5.4 years. Using SGA, 5.9% (n = 7) of the patients were classified as severely PEM, 27.7% (n = 33) were classified as moderately PEM, and 66.4% (n = 79) were classified as well nourished. Some 73.1% (n = 87) of the patients were followed in the ICU. Among all patients, 42.9% (n = 51) were fed by a combined enteral-parenteral route, 31.1% (n = 37) by an enteral route, 18.5% (n = 22) by a parenteral route, and 7.6% (n = 9) by an oral route. The average length of stay for the patients was 18.9 +- 13.7 days. The mortality rate was 44.5% (n = 53). The mortality rate was 43% (n = 34) in well-nourished patients (n = 79), 48.5% (n = 16) in moderately PEM patients (n = 33), and 42.9% (n = 3) in severely PEM patients (n = 7) (P = .86). The authors observed no difference between well-nourished and malnourished patients with regard to the serum protein values on admission, LOS, and mortality rate. In this study, malnutrition as defined by SGA did not influence the mortality rate of critically ill geriatric patients receiving enteral or parenteral nutrition. Furthermore, no factor was found to be a good predictor of survival. (JPEN J Parenter Enteral Nutr. 2008;32:454-459) Keywords: aged; malnutrition; enteral-parenteral nutrition

Protein-energy malnutrition (PEM) is a common disorder in hospitalized elderly patients. Malnutrition is reported to occur in a large number of elderly patients on admission to a hospital.1 Forty percent of elderly patients admitted to the hospital in the United Kingdom are undernourished, and half are severely undernourished.2 When defined as a decrease in nutrient reserve, malnutrition is prevalent in 1%-15% of ambulatory outpatients, 25%- 60% of institutionalized patients, and 35%-65% of hospitalized patients.3

Extensive documentation exists of the strong relationship between PEM in chronic disease and increased morbidity, mortality, and extended hospital stays.4,5 The causality of these connections is not clear. In addition, reduced food intake and breakdown of body tissues are partly the result of biochemical mechanisms activated by the disease. Although there are data indicating that nutrition enhancement may improve the outcome, contrary data exist in the literature.6,12

To determine the prevalence of malnutrition and to evaluate the clinical outcome in hospitalized patients aged 65 years and older receiving enteral-parenteral nutrition, we conducted this retrospective study in a university hospital.

Methods

The study includes geriatric patients of at least 65 years of age admitted to Baskent University Hospital between April 2000 and September 2002 who required nutrition intervention. Patients were evaluated by a nutrition support team. Subjective global assessment (SGA) was performed by the nutrition team dietician. Patients were classified into 3 groups according to SGA: (1) having PEM, (2) having moderate PEM or being at risk for PEM, and (3) being well nourished at admission. For patients followed in the intensive care unit (ICU), acute physiological and chronic health evaluation (APACHE-2) and simplified acute physiology scores (SAPS 2) were recorded. Patients who received no food were not separately recorded. Nutrition status was assessed within the first 24 hours after consultation and weekly during hospitalization with the use of serum proteins (serum albumin and prealbumin). These results were compared with mortality rate and length of hospital stay (LOS).

The patients’ total energy requirements were calculated by the Harris-Benedict equation adjusted by stress factors. The daily target protein requirements were calculated as 0.8-1.2 g/kg. Whenever possible, enteral nutrition was used (Standart; Isosource Standart, Novartis Laboratories, Switzerland, or specific for disease; Glucerna, Nutrena, or Pulmocare; Abbott Laboratories, the Netherlands) continuously infused into the stomach through a 14 Fr nasogastric polyurethane feeding tube (Flocare nasogastric pur tube; Nutricia Healthcare, Switzerland) with the aid of a peristaltic pump. We aimed the tip of the feeding tube in the distal stomach. The correct positioning of the feeding tube was verified by bolus infusion of 20 mL air while auscultating the epigastrium. During follow-up, the air auscultation method was used daily. The head of the patient’s bed was raised at least 45[degrees], which was verified by the nutrition team nurse. The enteral formula was commenced continuously through the feeding tube at a rate of 25 mL/ h. The rate was increased by 25 mL/h at 6-hour periods until the calculated maximum rate was reached. During the study, the residual volume was measured and recorded at 6-hour intervals. If the gastric residual volume was more than twice the current hourly infusion rate or was > 150 mL, the infusion rate was lowered to the previous rate, and the incident was recorded as “residue.” Digestive complications caused by enteral nutrition, such as nausea, vomiting, abdominal distention, and diarrhea were also recorded for each patient for each day. Enteral intolerance is defined as insufficient gastrointestinal functions, chronic vomiting, or diarrhea. An inadequate nutrition session was defined as the provision of

Table 1. Most Common Clinical Diagnoses on Admission

Statistical analyses were performed with SPSS for Windows (release 8.0). Simple descriptive statistics were used for demographic analyses. Between 2 independent groups, continuous values were compared by Student t test or unpaired t test. Proportions were compared by the chi^sup 2^ test. One-way ANOVA was used to compare groups of 3. Only 9 patients were fed via the oral route. Because the group was small, this group was excluded from further analysis. This exclusion affected only the analysis using the feeding route. For multiple regression analysis, some variables were reclassified. The continuous variable LOS was separated, that is, LOS between 1 and 16 days and LOS more than 16 days (patients’ LOS median value was 16 days) and inadequate feeding period (1 for 1 to 5 days, 0 for >5 days). Other variables included in the model were feeding route (1 for enteral, 0 for enteral-parenteral), development of distention, the period of supporting mechanical ventilation, and the period of nasogastric feeding tube. The mean age of the 119 patients included in this study was 73.15 +- 5.45 years, and 51% were male. The average time of hospitalization was 18.9 +- 13.7 days. Because of complications, the average duration of the inadequate feeding period was 6.3 +- 4.9 days.

The clinical diagnoses that were most prevalent within the study population at the time of admission are listed in Table 1. Of the group, 73.1% (n = 87) were followed in the ICU and 37.8% (n = 45) were supported by mechanical ventilation. Malnutrition was present in 40 (33.6%) of the 119 included patients (Figure 1).

Results

We observed no differences in serum protein values on admission and the LOS between well-nourished and malnourished patients (Table 2).

Figure 1. Assessment of malnutrition according to the subjective global assessment.13 Prevalence of malnutrition was present in 40 (33.6%) of the 119 included patients.

Table 2. Serum Protein Values on Admission and Length of Hospital Stay in Well-Nourished and Malnourished Patients

Table 3. APACHE-2 and SAPS 2 Values in the Intensive Care Unit

Of the 79 well-nourished patients, according to SGA, 79.7% (n = 63) were followed in the ICU. The malnutrition rate in the ICU was 27.6% (n = 24). APACHE-2 and SAPS 2 scores were higher in severely PEM patients, but that was not statistically significant (Table 3). Among all patients, 42.9% (n = 51) were fed by enteral-parenteral route, 31.1% (n = 37) were fed by enteral-only route, 18.5% (n = 22) by parenteral route, and 7.6% (n = 9) by oral route. In patients who received parenteral nutrition, the route was central in 34.5% (n = 41) and peripheral in 26.9% (n = 32). Central parenteral nutrition was used for all 22 patients in whom enteral nutrition was not used. In patients who received enteral nutrition (n = 37), 54.1% (n = 20) had a blood glucose measurement > 150 mg/dL. This was 64.7% (n = 33) in patients who received enteralparenteral nutrition and 36.4% (n = 8) in patients who received parenteral nutrition (n = 22; P = .065).

In patients who received enteral nutrition (n = 37), 83.8 % (n = 31) achieved the goal rate. The enteral intolerance rate was 25.9%. The complications are shown in Table 4.

The daily target total energy requirements were calculated by the Harris-Benedict equation. The ratio of patients who reached this target was 68.6% (n = 35) in enteral-parenteral- supported patients (n = 57). This figure was 50% (n = 11) in patients who received only parenteral supplementation (n = 22; P = .02). The reasons in which enteral nutrition was not used in the latter group were as follows: 1 case of gastrointestinal bleeding, 1 case of pancreatitis, 11 cases of postoperative abdominal surgery, 4 cases of risk of pulmonary aspiration, and 5 patients who did not take enough oral diet.

We observed no differences on the serum albumin or serum prealbumin values on admission (P = .78) and after nutrition support (P = .35).

Table 4. Complications Among All Patients Receiving Enteral- Parenteral Nutrition

Table 5. Variables Predicting Length of Stay

Figure 2. Mortality rate and malnutrition. PEM indicates protein- energy malnutrition.

Table 6. Effect of Serum Protein Levels on Admission and Relation With Mortality

Logistic regression analysis showed that among the variables predicting LOS, inadequate feeding period and the duration of nasogastric tube feeding proved to be significant (Table 5).

Among all patients, the mortality rate was 44.5% (n = 53). The relation between mortality and serum protein levels on admission is shown in Table 6. Low serum albumin and prealbumin levels on admission did not affect mortality (P = .39, P = .72, respectively).

The mortality rate was 47.5% in patients with moderate and severe PEM, and 43.0% in well-nourished patients. Malnutrition according to SGA did not affect the mortality rate (P = .74; Figure 2).

Mortality was also related to vomiting during nutrition support, gender, and nutrition complications (P = .01, P= .04, P = .05, respectively). The mortality rate was 64.9% in men and 35.1% in women. However, we did not find any independent variables that affect mortality by regression analysis.

Conclusion

Evaluating nutrition status in elderly patients is difficult because of inadequate nutrition parameters. In particular, age- related chronic diseases affect nutrition status.14 The clinical assessment of nutrition status in elderly patients is difficult. However, body composition, particularly muscle mass and fat distributions, are important parameters. These changes could have been evaluated by subjective physical assessment. Therefore, weight loss and nutrition assessment are important parameters. It has been reported that using the SGA for elderly patients (older than 70 years) for malnutrition assessment is safe and valid.15 In this study, malnutrition prevalence assessment by SGA was 33.6%. However, the malnourished patients’ serum protein levels on admission were similar to that of well-nourished patients. As the energy requirements were calculated, we took into account stress factors. Although this practice may not be advocated by some authors for geriatric patients, our policy is to supply additional calories for additional stress.

We observed no differences on the serum albumin or serum prealbumin values on admission (P = .78) and after nutrition support (P = .35). We could not observe any change, probably because of the short duration of nutrition support (average, 10.95 +- 9.55 days). Bos et al16 reported that short-term protein and energy supplementation (10 days) in hospitalized malnourished geriatric patients did not affect biochemical parameters.

The decline in serum albumin concentration in hospitalized patients is due to decreased albumin synthesis.17 In the literature, the relationship between low serum albumin levels and mortality is remarkable: Mortality is 1.7% in patients whose albumin level is 35 g/L and 62% in those with serum albumin levels

In this study, the rate of mortality was high in both groups (malnourished vs nourished; P = .74). As a policy, when we were consulted for giving nutrition support, it was given to all patients without distinguishing the patient’s general condition or prognosis. Although the mortality rate of patients with malnutrition was high compared with well-nourished patients, the difference was not significant (P = .25).

Researchers have stated that mortality rate is affected by cancer, infection, old age (>/=60 years), and clinical treatment, but the existence of malnutrition is an independent factor affecting mortality. Moreover, researchers have pointed out that disease and nutrition interact, and question whether disease causes malnutrition or whether malnutrition negatively affects the disease.19 Thus, researchers have put forward that it is hard to say from the poor clinical results whether malnutrition on its own is responsible.19 In this study, we could not detect any relationship between malnutrition as measured by the SGA and mortality. Moreover, nutrition support did not influence the outcome. This could be linked to the relatively short stay of the patients, as this period may not be sufficient to detect a difference caused by nutrition support. Therefore, it is advised that patients with malnutrition should be followed after being discharged from the hospital. We believe that malnutrition is effective in a patient’s outcome, but the condition of the patient and the disease seems to be more decisive for the prognosis. We need more comprehensive studies to explain the relationship between malnutrition and mortality, to see the positive effects of nutrition support given to malnourished patients on nutrition parameters, and to get more definite results. Preventing the progress of malnutrition, assessing, and following elderly patients starting from the beginning of their stay in the hospital by regarding their enteral nutrition; giving extra nutrition support in a suitable way without deteriorating the patient’s general condition; giving long-term support to obtain improvement in nutrition parameters; and following the patient after outcomes are important steps toward improving the clinical results.

References

1. Sobotka L. Klinik Nutrisyon Temei Kavramlar, ESPEN Kurslar Yayini, Ikinci Baski, Logos Yayincihk. Istanbul; 2000.

2. Allison SP, Rawlings J, Field J, Bean N, Stephen AD. Nutrition in the elderly hospital patient Nottingham Studies. J Nutr Health Aging. 2000;4:54-57.

3. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part 1: history, examination, body composition and screening tools, Nutrition. 2000;16:50-63.

4. Pennington CR. Disease-associated malnutrition in the year 2000. Postgrad Med J. 1998;74:65-71.

5. Sullivan DH. The role of nutrition in increased morbidity and mortality. Clin Geriatr Med. 1995;11:661-674.

6. Akner GA, Cederholm T. Treatment of protein-energy malnutrition in chronic nonmalignant disorders. AmJ Clin Nutr. 2001;74:6-24.

7. Milne AC, Potter J, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev. 2005;(2):CD003288.

8. Gadek JE, DeMichele SJ, Karlstad MD, et al. Effect of enteral feeding with eicosapentaenoic acid, gamma linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med. 1999;27;1409- 1420.

9. Elamin E, Hughes L, Drew D. Effect of enteral nutrition with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome (ARDS) [abstract]. Chest. 2005;128:225S. Abstract 3472K.

10. Mayes T, Gottschlich M, Carman B, Kagan R. An evaluation of the safety and efficacy of an anti-inflammatory, pulmonary enteral formula in the treatment of pediatric burn patients with respiratory failure [abstract]. Nutr Clin Pract. 2005;20:30-31. Abstract N027.

11. Singer P, Theilla M, Fisher H, Gibstein L, Grozovski E, Cohen J. Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med. 2006;34:1033-1038.

12. Pontes-Arruda A, Aragao AM, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, gammalinolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med. 2006;34:1033-1038.

13. Detsky A, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11:8-13. 14. Covinsky KE, Covinsky MH, Palmer RM, Sehgal AR. Serum albumin concentration and clinical assessments of nutritional status in hospitalized older people: different sides of different coins? J Am Geriatr Soc. 2002;50:631-637.

15. James JP, Grimble G, Silk D. Artificial Nutrition Support in Clinical Practice. 2nd ed. London, UK: Cambridge University Press; 2001.

16. Bos C, Benamouzig R, Bruhat A, et al. Nutritional status after short-term dietary supplementation in hospitalized malnourished geriatric patients. Clin Nutr. 2001;20:225-233.

17. Duerksen DR, Yeo TA, Siemens JL, O’Connor MP. The validity and reproducibility of clinical assesment of nutritional status in elderly. Nutrition. 2000;16:740-744.

18. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part 2: laboratory evaluation. Nutrition. 2000;16:131-140.

19. Isabel M, Correia TD, Waitzberg DL. The impact of malnutrition on morbidity, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr. 2003;22:235-239.

Betul Gulsen Atalay, MSc; Cahide Yagmur, PhD; Tarik Zafer Nursal, MD; Hakan Atalay, MD; and Turgut Noyan, MD

Financial disclosure: none declared.

From the Department of Nutrition, Baskent University, Adana Teaching and Medical Research Center, Adana, Turkey (BGA); Department of Food Engineering, Cukurova University, Adana, Turkey (CY); Department of General Surgery, Baskent University, Adana Teaching and Medical Research Center, Adana, Turkey (TZN, TN); and Department of Cardiovascular Surgery, Baskent University, Adana Teaching and Medical Research Center, Adana, Turkey (HA).

Address correspondence to: Betul Gulsen Atalay, Cukurova University, Department of Food Engineering, Adana 01250, Turkey; e- mail: [email protected].

Copyright American Society for Parenteral and Enteral Nutrition Jul/ Aug 2008

(c) 2008 JPEN, Journal of Parenteral and Enteral Nutrition. Provided by ProQuest LLC. All rights Reserved.

By Paauw, James D Borders, Heather; Ingalls, Nichole; Boomstra, Sarah; Lambke, Susan; Fedeson, Brian; Goldsmith, Austin; Davis, Alan T

Background: Indications for peripherally inserted central catheters (PICC) for long-term venous access have grown dur- ing the last several years. There are various complications associated with PICC lines, a common one being venous thrombosis. This study’s purpose was to determine the inci- dence of venous thrombosis associated with PICCs with and without prophylactic anticoagulants. Methods: In this observa- tional, prospective, cohort study, patients with PICC lines were evaluated using Doppler ultrasound for the presence of PICC-associated venous thrombosis at 5-7 days and again at 12-14 days after line placement. When present, clinical signs and symptoms of thrombosis were documented. Fifty-six patients were evaluated for the type of anticoagulation used, if any, and other clinical parameters such as smoking, ambula- tion, and previous surgery. The incidence of thrombus was then calculated for the entire population as well as for specific patient subgroups. Results: Patient age was 55.7 +- 2.6 (mean +- SEM) years, and BMI was 28.2 +- 1.2 (n = 56). There were 38 (67.9%) nonambulatory subjects, 15 (26.8%) smokers, 4 (7.1%) coagulopathic subjects, 2 (3.6%) patients receiving estrogen-containing medications, 25 (44.6%) who had undergone surgery within the past 6 months, and 5 (8.9%) cancer patients. There were 21/56 patients (37.5%) with thrombus. Patients who received anticoagulation had a 22.9% (8/35) incidence of thrombosis, which was significantly less (P

The placement of a peripherally inserted central catheter (PICC) for central venous access came into common usage in the mid 1970s and has expanded dramatically since then.1-3 However, no recent survey data are available on the volume of PICC placement nationwide. Because of the variable success rate and relatively high malposition rate (25%) associated with “blind” bedside PICC insertion,4 ultrasound-guided PICC insertion services have been established at many institutions, further enhancing the popularity of PICC usage. This popularity has come at the expense of other central venous catheter (CVC) techniques, such as subclavian or jugular and tunneled centrally inserted central catheters (CICC), due to the perceived advantages of PICCs. These advantages include ease of placement, greater cost-effectiveness, and safety.3-6

With regard to safety, however, there is some controversy. While virtually eliminating the risk of pneumothorax associated with CICCs, the use of PICCs has raised the question of associated incidences of venous thrombosis. The clinical significance of PICC- related upper extremity venous thrombosis (PRUEVT) is manifested by the risk of pulmonary embolism associated with CVC-related upper extremity venous thrombosis, which may be about 12%-17%.7 The incidence of PRUEVT has been reported to be anywhere between 0% and 56%.8-11 The wide variance in reported incidences is likely impacted by the heterogeneity of study conditions, including diagnostic technique, prospectivity, and whether assaying for clinically symptomatic or “silent” PRUEVT.

Another question related to PRUEVT is the preventability of this entity. Few studies have assessed the efficacy of prophylactic anticoagulant therapy on the prevention of PRUEVT. In a retrospective study, prophylactic use of unfractionated heparin or low molecular weight heparin did not significantly reduce the incidence of venous thrombosis in patients with either PICCs or CICCs.12 Conversely, a meta-analysis has found that the use of prophylactic low-dose heparin results in a significant reduction in CICC-related and arterial catheter- related upper extremity venous thrombosis.13 In this light, we conducted a prospective study of the incidence of silent PRUEVT and the efficacy of prophylactic anticoagulant therapy in the prevention of PRUEVT in patients with ultrasound-guided PICC placement. Prophylactic anticoagulant therapy, as used in this study, does not refer to routine line maintenance, such as flushing with heparin or the use of positive- pressure needleless adapters.

Methods

This prospective, observational cohort study was performed at Spectrum Health Butterworth Campus, Grand Rapids, MI. Written informed consent, approved by the local institutional review board, was obtained from all subjects prior to entry into the study. In- patients who required PICC lines for central venous access were selected for inclusion in the study. The PICC lines were used to deliver parenteral nutrition and/or antibiotics. Any patients with known coagulopathies were excluded.

Insertion of the catheter followed the protocol for PICC insertion per the Interventional Radiology Department of our institution. AU PICC lines were 5 Fr double lumen. Subjects were evaluated by ultrasound for the presence of associated venous thrombosis at 5-7 days and again at 12-14 days after PICC placement. A GE ultrasound machine (Logiq 9; GE Healthcare, Wauwatosa, Wis) and an 8 MHz linear probe were used. The vessel containing the PICC was evaluated, as were the axillary and lateral subclavian veins, using graded compression ultrasound and color flow Doppler imaging when necessary. A number of patients were found to have only a small rim of thrombus around the insertion site with no anterograde propagation of the thrombus or luminal compromise. These thrombi were classified as insertional trauma, and the patients were counted as thrombus-negative for study purposes. Only those patients with thrombus extending antegrade from the insertion site for at least 2 cm were counted as positive for study purposes. Clinical signs and symptoms of thrombosis were also documented when present. Patients were evaluated for the type of anticoagulation used, if any, as well as for other clinical parameters such as smoking, ambulation, and previous surgery. The incidence of PRUEVT (%) was then determined for the study sample as a whole, as well as for specific subgroups of patients.

Summary statistics for quantitative data are described as the mean +- SEM, while nominal data are expressed as a percentage. The t test was used to determine differences for quantitative variables, while the chi^sup 2^ test was used to determine differences for the nominal variables. Significance was determined at P

Results

Evaluable data were obtained for 56 subjects. The data are described in Table 1 . With regard to the demographic and clinical descriptors, there were no statistically significant differences between the 2 groups. There were 21 patients (37.5%) with a PICC line who had thrombus. All PICCs were in the basilic vein, and all catheter-related thrombi began at or immediately adjacent to the vessel insertion site and propagated centrally. A statistically significant increase in the incidence of PRUEVT was noted for the patients with no anticoagulation, relative to those subjects receiving some form of anticoagulation. No significantly increased incidence of PRUEVT was associated with any of the other clinical or demographic variables. At least 1 patient with PICC-associated thrombus developed a pulmonary embolus, which was shown to be PICCrelated by 4-extremity Doppler ultrasound and the presence of an inferior vena cava filter.

Discussion

Venous thrombosis is a well-known complication of CVC placement, but the actual incidence is not well defined. Reported incidences vary greatly depending on a number of factors, including venous location, length of dwell time, type of patient, and method of assay. In a review of studies of long-term, mostly tunneled CVCs in cancer patients, the reported incidence of clinically overt upper extremity deep vein thrombosis (DVT) varied between 0.3% and 28.3%. When studied by venography, the reported incidence rose to between 27% and 66%, most of which were asymptomatic.14 Reported incidences of venous thrombosis related to short-term, nontunneled CVCs also vary widely. In a study of 142 single lumen catheters using Doppler ultrasound or venography in patients with clinically suspected venous thrombosis, none was detected.15 However, in another study of single lumen and double lumen short-term CVCs using routine digital subtraction angiography on the seventh catheter day, the incidence of central venous thrombosis was found to be 40%, despite use of subcutaneous heparin at a daily dose of 5000 units.16 In this report, the number of lumens did not affect the development of thrombosis. Short-term catheterization of the internal jugular vein seems to carry one of the highest risks for venous thrombosis. Despite prophylactic anticoagulation, Doppler ultrasound demonstrated a 56% incidence of thrombus by day 4 in cardiac surgery patients.17 In a similar study of 63 consecutive critical care patients with internal jugular CVCs, all receiving either low-dose or therapeutic heparin, 40 patients (63.5%) were found to have venous thrombosis.18

Table 1 . Patient Data(a) It is generally accepted that PICCs, because they are placed in a smaller caliber vessel than CICCs, are more thrombogenic due to altered flow dynamics. In general, venous catheters cause the release of thromboplastic substances from catheter-associated intimai damage. These substances, in turn, activate the coagulation cascade, which leads to intraluminal thrombus formation. There are a number of suggested causative factors in catheterrelated thrombosis. These include vessel wall insertional trauma,19 endothelial abrasion due to IV catheter movement,20 and venous flow occlusion due to large catheter size relative to lumen size.20 One study using multivariate analysis directly linked PICC diameter to thrombosis rate.21 Symptoms of venous thrombosis, including localized redness, swelling, and pain, should prompt clinicians to initiate diagnostic studies to evaluate for PRUEVT. However, as was the case in this study, the majority of upper extremity PICC-related thrombi remain asymptomatic, delaying diagnosis of this entity. The true incidence of PRUEVT remains elusive, as many studies to date have evaluated only symptomatic patients with imaging or have used a retrospective method. These approaches lead to an underreporting of the incidence of PRUEVT. As a result, reported incidence varies widely by institution and by medical and clinical patient parameter 1-3,6,8-10,22 The higher incidence of PRUEVT in more recent retrospective studies is likely due to the liberal use of duplex Doppler ultrasound scanning as a result of increased awareness of the entity. The variance in reported incidence of PRUEVT led us to undertake a prospective survey approach in order to determine more accurately the actual incidence of PRUEVT in a hospital patient population.

The gold standard for evaluating PRUEVT is venography, which is invasive, costly, and involves the risk of IV contrast as well as a measure of physical discomfort. As a consequence, ultrasound is currently the more accepted technique for diagnosis of PRUEVT. The main criteria used in Doppler ultrasound for PRUEVT are mural thrombi or incompressibility of the vein, absence of spontaneous flow or presence of turbulent flow, lack of transmission of cardiac pulsatility, and observation of increased venous collaterals.14 The accepted standard to exclude the presence of thrombosis is 2 negative-compression ultrasound studies 1 week apart, as was used in the present study.1,23,24

Previously, use of minidose warfarin has been shown to reduce the incidence of CVC-related thrombosis in patients with hematological malignancies.2,26 In the former study, upper li mb DVT was reduced from 37.5% to 9.5%. In a prospective study, daily daltoparin 2500 units for 30 days reduced the incidence of venography-confirmed upper limb DVT from 62% in controls to 6% in the treatment group in cancer patients.27 A meta-analysis of randomized, controlled trials in CVC patients showed an overall efficacy by heparin in prevention of thromboembolic complications.28 Studies from this analysis included the use of various doses of subcutaneous heparin, heparin added to parenteral nutrition, and heparin bonding of catheters. In a comparison of minidose warfarin and low molecular weight heparin (nadroparin) in cancer patients, 28.6% of the nadroparin group and 16.7% of the warfarin group had venography-confirmed CVC-related DVT at 90 days.29 A systematic review of studies of thrombosis prophylaxis in CVC patients showed warfarin and dalteparin did reduce this risk in cancer patients, while the addition of heparin to parenteral nutrition did not significantly decrease thrombosis risk from CVCs.30 The studies included in this review focused on CVCs of subclavian, jugular, and femoral insertion sites, but not PICCs.

The current study found that prophylactic anticoagulation served to significantly decrease the incidence of PRUEVT, and thus the associated potential secondary complications. Complications of prophylactic anticoagulation, such as bleeding or heparin-induced thrombocytopenia (HIT) were not seen in any of the patients in this study. The study is unique in that it prospectively evaluated all patients with PICCs, thereby reflecting a more accurate PRUEVT incidence rate than previous retrospective or symptomatic-only studies. In addition, most previous studies of catheter-related venous thrombosis focused on a significantly longer dwell time than the current study. To date, there has been little suggestion in the literature of a significant incidence of PRUEVT at the early time period noted in this study.

This study has demonstrated that the true incidence of PRUEVT is considerably higher than has been previously reported.1-3,6,8-10,22 Routine ultrasound surveillance allowed for a more accurate measure of the actual extent of thrombotic disease associated with the use of PICCs. Another unforeseen finding in this study was a higher than expected incidence of PRUEVT in patients receiving prophylactic anticoagulation. Routine prophylactic anticoagulation of hospital patients is considerably more effective at preventing DVT of the lower extremities than it is in preventing PRUEVT.6,8,11-13 For example, the Medenox study of prophylaxis of venous thromboembolism in medical patients showed that the administration of daily enoxaparin reduced asymptomatic DVT from 14.5% to 5.5%,31 while in the PREVENT study, the incidence of DVT was reduced to 2.77% (from 4.96%) by 5000 units of dalteparin.32 The relatively weaker efficacy of prophylaxis in preventing PRUEVT relates to at least 3 factors involved in promoting PRUEVT. The first has been mentioned earlier, in that PICC placement causes catheter-related intimai damage, which is not usually a factor in the development of DVT in the lower extremities. The second, also previously alluded to, is the smaller vessel lumen diameter in the arm, with different flow mechanics than the larger vessels of the leg. Finally, the presence of an indwelling catheter not only compromises the volume of the vessel but presents a nidus for propagation of a clot.

The correlation between the high incidence of Doppler-proven PRUEVT reported here and its more serious potential sequelae, such as pulmonary embolism (PE), infected thrombus and associated sepsis, and postphlebitic syndrome, cannot be determined from the current study. The incidence of clinically observable PE associated with upper extremity venous thrombosis is estimated at about 12%,8,33,34 and is likely between 15% and 25% in cancer patients. 3,36 The incidence of PE was found to be greater from catheter-related upper extremity DVT (17%) than from primary DVT of the upper extremity (6%).36 This risk is lower than the accepted 50% risk of PE from lower extremity DVT for reasons reviewed elsewhere.36 It nonetheless represents a significant clinical risk, given the increasing number of hospital patients receiving PICCs and the high risk of early PRUEVT reported in this study.

Aside from the acute risk of thrombosis, there is a more chronic complication associated with PRUEVT known as postphlebitic syndrome. This syndrome is caused by valvular injury and outflow obstruction, is characterized by pain, chronic limb edema, functional impairment of the limb, and skin ulcerations. In 1 prospective study, 4 out of 1 5 patients followed for 2 years after diagnosis of upper extremity venous thrombosis demonstrated the presence of moderate to severe postphlebitic syndrome.7 Further investigation is needed to elucidate the actual risk of this entity and other serious sequelae from PRUEVT.

Anecdotally, while only one patient in this study was documented to have a PE, that patient was 1 of 3 patients of whom the authors were made aware during the course of the study who developed PRUEVT- related PE. The other patients had not been entered into the study. Each patient had an inferior vena cava filter in place, and PRUEVT- related PE was established by 4-extremity ultrasound.

Although the sample size is relatively small, this study suggests that the use of prophylactic anticoagulation to reduce the risks associated with PRUEVT outweighs the risks associated with the use of these therapies. We feel that given the unexpectedly high incidence of early PRUEVT in nonprophylaxed patients in this study, along with the proven efficacy of prophylactic anticoagulation to reduce this incidence, in the absence of contraindications, patients with PICCs should be considered for such therapy. In patients in whom anticoagulation is contraindicated or who are at higher risk than the general population for thromboembolic disease, consideration should be given to placement of subclavian CVCs instead of PICCs. Moreover, the 23.5% incidence of PRUEVT in the face of prophylactic anticoagulation should lead clinicians to have a low threshold for the use of Doppler ultrasound in patients with PICCs with even early signs of thrombosis.

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13. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a metaanalysis. Chest. 1998;113:165-171.

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15. Murphy PT, O’Connor N. Low risk of central venous thrombosis with nontunnelled central venous catheters. Clin Lab Haem. 2001;23:187-188.

16. Koksoy C, Kuzu A, Erden I, Akkaya A. The risk factors in central venous catheter-related thrombosis. Aust NZ J Surg. 1995;65:796-798.

17. Wu X, Studer W, Skarvan K, Seeberger M. High incidence of intravenous thrombi after short-term central venous catheterization of the internal jugular vein. J Clin Anesth. 1999;11:482-485.

18. Karnik R, Valentin A, Winkler W-B, Donath P, Slany J. Duplex sonographic detection of internal jugular venous thrombosis after removal of central venous catheters. Clin Cardiology. 1993:16:26- 29.

19. Ross A, Griffith C, Anderson J. Thromboembolic complications with silicone elastomer subclavian catheters. JPEN J Parenter Enteral Nutr. 1982;6:61-63.

20. Eastbridge BJ, Lefor AT. Complications of indwelling intravenous catheter devices in cancer patients. J Clin Oncol. 1995;13:233-238.

21. Grove JR, Pevec WC. Venous thrombosis related to peripherally inserted catheters. J Vasc Interv Radiology. 2000;11:837-840.

22. Walshe LJ, Malak SF, Eagan J, Sepkowitz KA. Complication rates among cancer patients with peripherally inserted central catheters. J Clin Oncol. 2002;20:3276-3281.

23. Elliot G. Upper-extremity deep vein thrombosis. Lancet. 1997;349:1188-1189.

24. Fraser JD, Anderson DR. Deep venous thrombosis: recent advances and optimal investigation with US. Radiology. 1999;211:9- 24.

25. Bern HM, Lokich JJ, Wallach SR, et al. Very low dose of warfarin can prevent thrombosis in central venous catheters: a randomized, prospective trial. Ann Intern Med. 1990;112:423-428.

26. Boraks P, Seale J, Price J, et al. Prevention of central venous catheter-associated thrombosis using minidose warfarin in patients with haematological malignancies. Br J Haematol. 1998;101:483-486.

27. Monreal M, Alastrue A, Rull M, et al. Upper extremity deep venous thrombosis in cancer patients with venous access devices: prophylaxis with a low-molecular weight heparin (Fragmin). Thromb Haemost. 1996;75:251-253.

28. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a metaanalysis of randomized controlled trials. Chest. 1996; 113:165- 171.

29. Mismetti P, Mille D, Laporte S, et al. Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial. Haematologica. 2003;88:67-73.

30. Klerk CPW, Smorenburg SM, Buller HR. Thrombosis prophylaxis in patient populations with a central venous catheter. A systematic review. Arch Intern Med. 2003;163:1913-1921.

31. Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients: prophylaxis in medical patients with enoxaparin study group. N Engl J Med. 1999;341:793-800.

32. Vaitkus PT, Leizorovicz A, Goldhaber SZ. PREVENT investigator group. Vasc Med. 2002;7:269-273.

33. Horattas MC, Wright DJ, Fenton AH, et al. Changing concepts of deep vein thrombosis of the upper extremity. Report of a series and review of the literature. Surgery. 1988;104:561-567.

34. Marie I, Levesque H, Cailleaux N, et al. Deep vein thrombosis of the upper limbs: apropos of 49 cases. Rev Med Interne. 1998;19:399-408.

35. Monreal M, Raventos A, Lerma R, et al. Pulmonary embolism in patients with upper extremity deep vein thrombosis associated to central venous lines: a prospective study. Thromb Haemos. 1994;72:548-550.

36. Kooi JD, vander Zant FM, van Beek EJ, Reekers JA. Pulmonary embolism in deep vein thrombosis of the upper extremity: more often in catheter-related thrombosis. Neth J Med. J 1997:50:238-242.

James D. Paauw, MD, PhD1; Heather Borders, MD2; Nichole Ingalls, MD3; Sarah Boomstra1; Susan Lambke4; Brian Fedeson, MD2,4; Austin Goldsmith, MD3; and Alan T. Davis, PhD3,5,6

Financial disclosure: none declared.

From 1 Spectrum Health Metabolic Nutrition Support Service, 2 GBMERC/MSU Radiology Residency, 3 GRMERC/MSU General Surgery Residency, 4 Spectrum Health Interventional Radiology Service, 5 Departments of Surgery, Michigan State University and Spectrum Health, and 6 GRMERC Department of Research, Grand Rapids, MI.

Received for publication June 11, 2007; accepted for publication January 25, 2008.

Address correspondence to: Alan T. Davis, PhD, Michigan State University, GRMERC, 1000 Monroe NW, Grand Rapids, MI 49503; e-mail: [email protected].

Copyright American Society for Parenteral and Enteral Nutrition Jul/ Aug 2008

(c) 2008 JPEN, Journal of Parenteral and Enteral Nutrition. Provided by ProQuest LLC. All rights Reserved.

Page H. Vaughan has been appointed senior vice president and division CEO of Midwest City Area Hospital Operations by Health Management Associates Inc.

Vaughan will have leadership responsibility for HMA’s Midwest City area hospital operations, including the Oklahoma Heart Hospital South campus joint venture.

He was senior vice president and divisional CEO for HMA’s North and South Carolina hospitals. Vaughan began his career with HMA in 1991 as an assistant administrator at Highland’s Regional Medical Center in Sebring, Fla.

Vaughan received a master’s degree in health administration from Virginia Commonwealth University’s Medical College of Virginia in Richmond.

Midwest Regional is a 255-bed acute medical and surgical hospital. HMA, based in Naples, Fla., owns and operates 57 hospitals.

Originally published by Journal Record Staff.

(c) 2008 Journal Record – Oklahoma City. Provided by ProQuest LLC. All rights Reserved.

PORTLAND, Ore., Sept. 4 /PRNewswire/ — Obese people who have asthma are nearly five times more likely to be hospitalized for the condition than non-obese people with asthma, according to a Kaiser Permanente study published in the September issue of the Journal of Allergy and Clinical Immunology.

This is the first study to control for the risk factors — smoking, use of oral or inhaled corticosteroid medications, gastroesophageal reflux disorder, and demographics — that might explain the obesity-asthma association. Previous studies have shown that obese people are more likely to suffer asthma than non-obese people, and that obese patients often have more severe asthma than their non-obese counterparts.

More than 20 million Americans have been diagnosed with asthma. Nearly a third of adults with asthma are also obese, according to researchers. The Centers for Disease Control and Prevention defines obesity as having a Body Mass Index of 30 or higher (http://www.cdc.gov/nccdphp/dnpa/obesity/defining.htm)

Researchers at Kaiser Permanente Center for Health Research in Portland, Ore., and the Kaiser Permanente Institute for Health Research in Denver surveyed 1,113 patients in Oregon, Washington, and Colorado, age 35 and older, who have persistent asthma. The researchers asked the patients about their weight, height, smoking habits, other illnesses, treatment and their asthma-specific quality of life, asthma control and asthma-related hospitalizations.

“The big finding here is that even after adjusting for risk factors, obese adults were nearly five times more likely to be hospitalized for their asthma,” said study lead author David M. Mosen, Ph.D., MPH, of the Kaiser Permanente Center for Health Research. “Given that nearly 30 percent of our country is obese, this study is yet another example of the long-term dangers of obesity, along with heart disease, diabetes, stroke and dementia.”

   The study uncovered these findings:    -- Obese people with asthma had significantly worse asthma control, lower      asthma-related quality of life, and had 4.6 times higher risk for      asthma-related hospitalizations than non-obese asthmatics   -- Obese people with asthma were younger and less educated than non-obese      people with asthma   -- Obese people with asthma used more oral corticosteroids   -- Obese people with asthma had a higher incidence of gastroesophageal      reflux disorder    

“The take-home message of this study for clinicians is that obese people with asthma need to be followed more carefully because it’s harder to control their asthma, so they are more likely to end up in the hospital,” said study co-author Dr. Michael Schatz, Chief of Allergy at Kaiser Permanente San Diego Medical Center. “My advice for obese asthmatics is: be vigilant to keep your asthma symptoms in check, make sure you know what to do when your symptoms worsen, and do whatever you can to lose weight.”

Funded by the Centers for Disease Control and Prevention, the study was authored by David M. Mosen, Ph.D., MPH of the Kaiser Permanente Center for Health Research; Michael Schatz, MD, MS, of Kaiser Permanente San Diego Medical Center; David J. Magid, MD, of the Kaiser Permanente Institute for Health Research in Denver; and Carlos A. Camargo, Jr., MD, DrPH, of the Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School.

About the Kaiser Permanente Center for Health Research (http://www.kpchr.org/)

Kaiser Permanente’s Center for Health Research, founded in 1964, is a nonprofit research institution dedicated to advancing knowledge to improve health. It has research sites in Portland, Ore., Honolulu, Hawaii and Atlanta.

About Kaiser Permanente Research

Kaiser Permanente’s eight research centers comprise one of the largest research programs in the United States and engage in work designed to improve the health of individuals everywhere. KP HealthConnect(TM), Kaiser Permanente’s electronic health record, and other resources provide population data for research, and in turn, research findings are fed into KP HealthConnect to arm physicians with research and clinical data. Kaiser Permanente’s research program works with national and local health agencies and community organizations to share and widely disseminate its research data. Kaiser Permanente’s research program is funded in part by Kaiser Permanente’s Community Benefit division, which in 2007 directed an estimated $1 billion in health services, technology, and funding toward total community health.

About Kaiser Permanente

Kaiser Permanente is America’s leading integrated health plan. Founded in 1945, the program is headquartered in Oakland, Calif. Kaiser Permanente serves 8.7 million members in nine states and the District of Columbia. Today it encompasses Kaiser Foundation Health Plan, Inc., Kaiser Foundation Hospitals and their subsidiaries, and the Permanente Medical Groups. Nationwide, Kaiser Permanente includes approximately 159,000 technical, administrative and clerical employees and caregivers, and 14,000 physicians representing all specialties. The organization’s Labor Management Partnership is the largest such health care partnership in the United States. It governs how more than 130,000 workers, managers, physicians and dentists work together to make Kaiser Permanente the best place to receive care, and the best place to work. For more Kaiser Permanente news, visit the KP News Center at: http://xnet.kp.org/newscenter

Kaiser Permanente

CONTACT: Farra Levin, +1-510-267-7364, [email protected], or DanielleCass, +1-510-267-5354, [email protected], both of Kaiser Permanente

Web site: http://www.kaiserpermanente.org/http://www.kpchr.org/

By Tim Puko

A higher-than-expected rate of youth suicides might be part of an emerging, nationwide health crisis, according to research co- authored by a Carnegie Mellon University professor released today.

The rate of youth suicides declined for more than a decade before spiking in 2004, according to the U.S. Centers for Disease Control and Prevention. Although the rate dropped slightly from 2004 to 2005, the most recent years for which statistics are available, it was much higher than trends suggest it should have been, according to the research published in the Journal of the American Medical Association.

“For 15 years you see something going down, and then all of a sudden you see a jump, and that jump stays up, that jump is a concern,” said Joel B. Greenhouse, the Carnegie Mellon statistician who co-authored the study.

“Here we’re talking about lives. Last year the federal government’s response to the jump was, ‘Let’s be cautious … this could be just a statistical fluke.’ Now we have two years of data, and it’s hard to argue that this is a statistical fluke.”

There were about nine suicides for every 200,000 American youths in 2005, according to the study. Suicide is the third leading cause of death in adolescents and the second among college-age youths, according to Mental Health America, formerly known as the National Mental Health Association.

The research adds to a growing list of reports that worry about an international rise in youth suicides. Several researches have noted a spike happened just after the U.S. Food and Drug Administration put messages on antidepressant packaging warning the drugs might increase the risk of suicide for children and young adults.

That was a motivation for the study, said Greenhouse and Jeffrey A. Bridge, the study’s principal investigator and an epidemiologist at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio. The next step should be for more studies to determine the cause of the rise, they said.

The two did a regression analysis of the suicide rates for U.S. children ages 10 to 19 from 1996 to 2005. This group’s suicide rate jumped 18 percent between 2003 and 2004, the largest single-year change in 15 years, according to federal data analyzed in the study.

The rate decreased by about 5 percent for 2005. However, if the 2004 spike was an anomaly, the 2005 decrease should have been more dramatic, about four times larger, according to the Bridge and Greenhouse study.

Bridge and Greenhouse give a few possible reasons for the increase in youth suicides, including the influence of Internet social networks and suicides among older teens who are U.S. soldiers. Other researchers have pointed directly at the so-called “Black Box” warning labels on antidepressants, noting an international correlation between the drug warnings and the spike in suicides.

Several researchers and advocates agreed that more awareness and education is crucial. Declines in suicide rates are rare, and people need to know that antidepressants are one of the few effective measures for suicide prevention, said Dr. David Schaffer, an adolescent psychiatrist at Columbia University Medical Center in New York.

CONTACT Pittsburgh, which offers emotional support and crisis intervention services, is starting a suicide training prevention program this fall to teach people how to support those at risk. Since 2006, the group has designated a staff member to talk at local high schools and colleges about suicide and prevention, Executive Director Christy Stuber said.

Suicide statistics for 2006 are expected to be available by late fall, Schaffer said.

(c) 2008 Tribune-Review/Pittsburgh Tribune-Review. Provided by ProQuest LLC. All rights Reserved.

By Dan Herbeck

Two girls were shot Monday evening as they played on the sidewalk in front of their home in the 200 block of Sprenger Avenue in Buffalo’s Schiller Park neighborhood, police reported.

A 13-year-old girl and her 7-year-old sister were the victims, according to Jay Smith, spokesman for Rural/Metro Medical Services, whose ambulances took the older girl to Erie County Medical Center and the younger girl to Women and Children’s Hospital of Buffalo.

“Neither of the injuries appear to be life-threatening,” Smith said.

Buffalo police spokesman Mike DeGeorge said that several men in a car pulled up to the girls shortly before 9:30 p.m. and fired.

The older girl was struck with birdshot and suffered numerous wounds in the face, chest and stomach, police said, and the younger girl was grazed in the back.

The shooting occurred four blocks from where 14-year-old Nancylia Salter was killed by gunfire last Tuesday. Sprenger runs south from Genesee Street near Schiller Park.

Asked if there was a connection, DeGeorge said, “It’s way too early to comment on that right now, except to say that we are looking into it.”

Police said they pulled over several men in a car not far from the scene shortly after the shooting and were questioning them.

A woman neighbor who came to the aid of the girls right after the shooting told The Buffalo News that the gunman shouted to the younger girl to get down, then started firing at the older girl.

“This is very upsetting,” the neighbor said. “No parent should have to go through the situation where their child has been shot.”

She added that the entire neighborhood is concerned about the shooting. “We all live here,” she said.

e-mail: [email protected]

Originally published by NEWS STAFF REPORTER.

(c) 2008 Buffalo News. Provided by ProQuest LLC. All rights Reserved.

A study has found that the babies involved in miscarriage had always failed to grow properly in the first few weeks of life.The research, on 292 women, revealed that the crown rump length (CRL) of the foetus was “significantly smaller” in pregnancies that subsequently ended in miscarriage.Dr Faizah Mukri, from the early pregnancy unit at St George’s Hospital in London, led the study, published in BJOG: An International Journal of Obstetrics and Gynaecology.Some 70 per cent of babies that were delivered normally at the end of pregnancy had a smaller than expected CRL in the first few weeks, she said.But all the babies involved in miscarriage had a smaller CRL, and 61 per cent of those had a far smaller CRL than expected, she added.Other research has suggested that the slow growth of the foetus could be the result of chromosomal abnormalities, which can be detected by a slow foetal heart rate during ultrasound scans. It could also relate to the possibility of the placenta not working properly, which restricts the normal growth of the foetus, thereby leading to the miscarriage.The latest study involved women who knew the exact date of their last period receiving an ultrasound scan between five and 10 weeks of gestation.The average age of the foetus at the ultrasound scan was seven weeks and the women were followed up several weeks later.Overall, 251 women had viable babies by the second scan. But 41 women had suffered a miscarriage.The authors wrote: “CRL was significantly smaller in pregnancies that subsequently ended in miscarriage. This suggests that early first trimester growth restriction is associated with subsequent intrauterine death.” Dr Mukri said the greater the difference between the observed and expected CRL at the time of the scan, the greater the risk of subsequent pregnancy failure before 12 weeks.Dr Mukri suggested that improved NHS scanning, although it would not affect the ultimate outcome of the pregnancy, could allow women to be offered counselling to reduce the psychological impact of a failed pregnancy.Professor Philip Steer, the journal’s editorinchief, said: “Miscarriage is heartaching for many women, especially firsttime mothers. However, it is more common than most people think and it is the body’s natural way to reject a foetus that is not growing normally.”

(c) 2008 Yorkshire Post. Provided by ProQuest LLC. All rights Reserved.

Microbial identification systems (MISs) are test systems that utilize multiple substrates and/or reagents to identify aerobic or anaerobic bacteria, yeasts, molds, or yeast-like algae grown from culture. MISs have become increasingly complex, which has resulted in the need for a greater number of quality control (QC) organisms to check positive and negative reactivity for all components. In 2005, the American Society for Microbiology (ASM), at the suggestion of the Clinical Laboratory Improvement Advisory Committee (CLIAC), conducted a microbiology laboratory survey to determine the QC failure rates of commercial MISs in a random selection of laboratories that perform bacterial and fungal identification from culture. The data showed a failure rate of less than 0.1% for all commercial MISs surveyed.

As a result, Clinical and Laboratory Standards Institute (CLSI) used its consensus process to develop Quality Control for Commercial Microbial Identification Systems; Approved Guideline (M50-A). This includes guidelines that may be followed when using an MIS of proven reliability to take a modified QC approach, rather than meeting requirements included in the Clinical Laboratory Improvement Amendments of 1988 regulations.

Nancy L. Anderson, MMSc, MT(ASCP), Chief, Laboratory Practice Standards Branch, Division of Laboratory Systems, National Center for Preparedness, Detection, and Control of Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) and Chairholder of the subcommittee that developed the document explains, “The QC requirements in the CLIA regulations state that a positive and negative control must be checked for every reagent or substrate on an MIS panel. As systems have developed and become more complex, this has resulted in a need for testing large numbers of organisms in order to check every reagent or substrate. In addition, there are now some MISs whose identification algorithms do not allow for total compliance with this QC requirement. Thus, in some cases, meeting the CLIA requirement is now impossible; whereas in other cases, it imposes financial and workflow burdens on microbiology laboratories and may be unnecessary for MISs of proven reliability produced by manufacturers that meet quality standards and regulations for control and distribution. Development of M50 provides a means for reducing resources spent on QC testing.”

The document specifies the QC responsibilities of the manufacturer, distributor, and user, and identifies conditions under which an MIS with proven reliability can qualify for streamlined QC testing.

For additional information on CLSI or for further information regarding this release, visit our website at http://www.clsi.org or call +610.688.0100.

CLSI, formerly NCCLS, is a global, nonprofit, membership-based organization dedicated to developing standards and guidelines for the health care and medical testing community. CLSI’s unique consensus process facilitates the creation of standards and guidelines that are reliable, practical, and achievable for an effective quality system.

HealthTronics, Inc. (NASDAQ: HTRN) announced today that it has sent a letter to the Endocare, Inc. (NASDAQ: ENDO) Board of Directors to reaffirm its proposal to acquire all of the outstanding shares of Endocare’s common stock for $2.28 per share.

In the letter, HealthTronics emphasized the resources it invests in technologies that it endorses for use in its physician partnerships. HealthTronics continually evaluates how the market might perceive the longer term viability and financial backing of a technology it favors, and HealthTronics is willing to take proactive measures to help support the continued success of a technology as a prior alternative to promoting a different technology.

HealthTronics also indicated its willingness to revise its proposal to allow each of the Endocare shareholders to elect to receive either cash or shares of HealthTronics common stock, provided that the total stock portion of the purchase price does not exceed a negotiated percentage of the total purchase price.

Commenting on the letter, James Whittenburg, President and Chief Executive Officer of HealthTronics, stated: “HealthTronics believes that the flexibility of our proposal in allowing Endocare shareholders to receive stock consideration will provide an opportunity for them to participate in the benefits of the combined company and a stronger long-term investment.”

Below is the text of the letter that HealthTronics sent to Endocare’s Board of Directors on September 3, 2008:

 September 3, 2008  Board of Directors Endocare, Inc. 201 Technology Drive Irvine, CA 92618 

Dear Members of the Board:

HealthTronics remains committed to its proposal to acquire all of the outstanding shares of Endocare’s common stock for $2.28 per share. We believe our firm proposal reflects a fair value for Endocare. Endocare communicated in its August 13, 2008 press release that its Board determined our proposal was inadequate. Despite our attempts to engage Endocare in a dialogue regarding our proposal, there has been no such dialogue. As a result, we are unclear as to why the Endocare Board believes our proposal is inadequate and what modifications to our proposal would, in the Board’s view, make it adequate. While we believe our proposal reflects a fair value for Endocare, we are willing to revise our proposal to allow each of the Endocare shareholders to elect to receive either cash or shares of HealthTronics common stock, with the stock portion of the consideration not to exceed a negotiated percentage of the total purchase price. This option to receive HealthTronics stock would enable Endocare shareholders to participate in the value and growth of the combined company.

HealthTronics continually strives to provide our urologist partners with leading-edge technologies that enable them to provide high-quality patient care. In so doing, we invest our time and resources to promote technologies that we believe meet the high standards of our urologist partners. When we promote the use of a particular technology, our reputation is linked to that product and, by association, the company that manufactures that product. For that reason, we are sensitive to perceptions concerning the longer term viability and financial backing of a technology we favor, and it is our first choice to proactively support the continued success of such a technology before seeking to replace that technology with one that is equally or more compelling.

Through our subsidiary, Advanced Medical Partners, Inc., we have demonstrated a strong commitment to Endocare’s technology and we believe that HealthTronics’ ownership of Endocare would maximize the value associated with the technology. The HealthTronics platform offers several advantages, including:

— well established relationships with approximately one-third of the practicing urologists in the United States;

— demonstrated successful promotion of the Endocare technology; and

— strong, positive cash flow and greater assurance of long-term financial solvency.

We believe our proposal represents both immediate certainty of value in a volatile stock market environment and a stronger long-term opportunity for your shareholders.

Our proposal remains subject to the negotiation of a definitive merger agreement and our having the opportunity to conduct certain limited and confirmatory due diligence.

My leadership team and I will continue to make ourselves available to meet with you to discuss all aspects of our proposal and answer any questions you may have at your earliest convenience.

We very much look forward to your prompt reply.

 Very truly yours,  /s/ James S. B Whittenburg  James S. B Whittenburg President and Chief Executive Officer 

About HealthTronics, Inc.

HealthTronics is a premier urology company providing an exclusive suite of healthcare services and technology including urologist partnership opportunities, surgical and capital equipment, maintenance services offerings, and anatomical pathology services. For more information, visit www.healthtronics.com.

Additional Information and Forward Looking Statements

Statements by the Company’s management in this press release that are not strictly historical, including statements regarding plans, objectives and future financial performance, are “forward-looking” statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. In particular, statements in this press release regarding future outlook or future revenue growth are forward-looking statements. Although HealthTronics believes that the expectations reflected in the forward-looking statements in this press release are reasonable, no assurance can be given that the expectations will prove to be correct. Factors that could cause actual results to differ materially from HealthTronics’ expectations include, among other things, HealthTronics’ ability to achieve the synergies and value creation contemplated by the proposed transaction, HealthTronics’ ability to timely and effectively integrate the business of Endocare, the timing to consummate the proposed transaction, the timing of obtaining and any necessary actions to obtain regulatory and other approvals, the existence of demand for and acceptance of HealthTronics’ products and services, maintaining relationships with physicians and hospitals, governmental regulations and changes thereto, regulatory approvals, economic conditions, the impact of competition and pricing, successful integration of acquired businesses, financing efforts and other factors described from time to time in HealthTronics’ periodic filings with the Securities and Exchange Commission.

The statements in this press release are made as of the date of this press release, even if the press release is subsequently made available by the Company on its web site or otherwise. The Company does not assume any obligation to update the forward-looking statements provided herein to reflect events that occur or circumstances that exist after the date hereof.

This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval. In connection with the proposed transaction, HealthTronics, Inc. plans to file with the SEC a registration statement on Form S-4 containing a prospectus and other documents regarding the proposed transaction. The prospectus will be mailed to stockholders of Endocare, Inc. INVESTORS AND SECURITY HOLDERS OF ENDOCARE, INC. ARE URGED TO READ THE PROSPECTUS AND OTHER DOCUMENTS FILED WITH THE SEC CAREFULLY IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION.

Investors and security holders will be able to obtain free copies of the registration statement and the prospectus (when available) and other documents filed with the SEC by HealthTronics, Inc. through the website maintained by the SEC at http://www.sec.gov. Free copies of the registration statement and the prospectus (when available) and other documents filed with the SEC can also be obtained by directing a request to Ross A. Goolsby, HealthTronics, Inc., 1301 Capital of Texas Highway, Suite 200B, Austin, Texas 78746.

MEDIA ADVISORY:

 WHAT:    Officials from the U.S. Food and Drug Administration Blood Products Advisory Committee (BPAC) will meet with government institutions and top experts from academia and private industry on September 10, 11 and 12 in two separate meetings to address issues related to safety of the blood supply including: -- Bacterial contamination of donated blood products for transfusion which can lead to sepsis (Sept. 10) -- Risk of infectious disease such as malaria from blood donors traveling abroad, and impact on donor pool and blood shortages (Sept. 11) -- Emerging concerns of U.S. diseases spread by ticks like babesiosis and lyme disease (Sept. 12)  WHY:     All of these organizations are committed to ensuring the safety of the nation's blood supply. Recent fines against the American Red Cross have shed public light on concerns around contaminants in the blood supply and areas for improving blood product safety. For example: -- 125 blood transfusion related fatalities were reported to the FDA in 2005 and 2006(1) -- 1 in 3,000 units of platelet blood components are believed to be bacterially contaminated at time of transfusion(2) putting 1 in 500 patients at risk for sepsis (based on an average of 6 units of platelets per transfusion) -- West Nile Virus took four years to identify and arguably more than 3,200 people were infected through blood transfusion(3) -- FDA reported a total of five deaths related to transfusion- transmitted babesiosis in 2006 and 2007(4)  The FDA BPAC and Department of Health and Human Services Advisory Committee on Blood Safety and Availability (ACBSA) have previously met to discuss strategies to improve blood safety, including pathogen inactivation, a proactive approach to eradicate bacteria, viruses and pathogens from the blood supply.  HOW:    Pathogen inactivation technologies have the ability to inactivate bacteria, viruses and parasites from donated blood that may not be detected by current diagnostic tests. Many European countries are currently using pathogen inactivation to safeguard their blood supply.  WHO:    Speakers will include representatives from the American Red Cross, Centers for Disease Control, academic and industry experts.  Learn more about areas for improvement of blood safety or to speak to an expert about pathogen inactivation and its anticipated benefits to the U.S. blood supply by speaking with: -- Dr. Jeff McCullough, M.D., American Red Cross Professor, Transfusion Medicine, Professor, Laboratory Medicine & Pathology, University of Minnesota -- Dr. Larry Corash, M.D., Chief Medical Officer, Cerus Corporation  WHEN / WHERE:  FDA Meeting: Blood Products Advisory Committee Sept. 10, 2008, 8:00 a.m. to 5:45 p.m. Sept. 11, 2008, 8:00 a.m. to 3:00 p.m. Hilton Hotel, Washington, D.C./Rockville Executive Meeting Center, 1750 Rockville Pike, Rockville, MD 20852 Complete BPAC Meeting Agenda: http://www.fda.gov/CbER/advisory/bp/bp0908.htm  FDA Workshop: Risk of Transfusion-Transmitted Babesiosis in the United States Sept. 12, 2008, 7:30 a.m. - 5:30 p.m. Lister Hill Center Auditorium, Building 38A, National Institutes of Health, 8800 Rockville Pike Bethesda, MD 20894 FDA Workshop Announcement: http://www.fda.gov/Cber/meetings/ttb091208.htm FDA Workshop Agenda: http://www.fda.gov/Cber/meetings/ttb091208ag.htm 

(1) FDA Web site http://www.fda.gov/cber/blood/fatal0506.htm as of Sept. 3, 2008

(2) CDC Web site at Fatal Bacterial Infections Associated with Platelet Transfusions found at this link http://www.cdc.gov/mmwR/preview/mmwrhtml/mm5407a2.htm as of May 9, 2008

(3) HJ Alter. Pathogen Reduction: A precautionary principle paradigm. Transfusion Medicine Reviews. Vol. 22, 2 April 2008

(4) FDA Web site announcing FDA Workshop to Consider Approaches to Reduce the Risk of Transfusion-Transmitted Babesiosis in the United States at http://www.fda.gov/cber/meetings/ttb091208.htm as of August 27, 2008

Health Canada is advising parents and caregivers of the dangers associated with balloon blowing kits. Anyone having them is urged to immediately take them away from children.

On August 20, 2008, Health Canada inspectors removed 1,574 children’s balloon blowing kits from sale at the Central National Exhibition (CNE) fairgrounds in Toronto, Ontario. Between August 15th and the 20th an unknown number of these prohibited toys were sold to the public at the exhibition. The toys were sold at three booths within the “International Pavilion” section of the CNE in the area identified as “Products of Philippines”.

Children’s balloon blowing kits have been banned in Canada since 1973. These toys typically consist of a solvent mixture in a tube and one or more plastic straws for blowing. Children can form balloons or bubbles by dipping the short straw into the solvent and blowing through the straw.

The safety concern is that blowing the balloons exposes a child to inhaling the vapours of any solvents present. Children can be fascinated with these products, and if they blow balloons for extended periods they may experience early symptoms of central nervous system depression or dysfunction, including euphoria, hallucinations, dizziness, and difficulties with coordination of voluntary movements. Prolonged exposure can lead to more serious symptoms including muscular twitching, unconsciousness, and coma.

These products should be safely disposed of in regular household trash in such a way that they cannot be reused.

There have been no illnesses or injuries to children reported to Health Canada related to the use of the balloon blowing kits recently removed from sale.

To report a safety-related concern with a consumer product, the public is advised to contact the Health Canada Product Safety office, toll-free, at 1-866-662-0666, or e-mail [email protected].

Egalement disponible en francais

A photo is available at the following address: http://file.marketwire.com/release/bal.jpg

 Contacts: Media Inquiries: Health Canada 613-957-2983  Public Inquiries: 613-957-2991 1-866-225-0709  

SOURCE: Health Canada

ORLANDO, Fla., Sept. 3 /PRNewswire/ — Statistics show that 90% of us will have High Blood Pressure in our lifetime, but that data doesn’t sit well with the people of Central Florida — they’re primed to fight the silent killer. Today, Orlando Mayor Buddy Dyer was joined by dozens of community and business leaders to announce a first of its kind health initiative to promote healthier outcomes for Central Floridians and issue a challenge for at least 1 million area residents to get their blood pressure checked through — Project Pressure. Organizers hope the Project will not only raise awareness of the dangers of hypertension in their region, but also motivate cities and communities nationwide to step up their blood pressure education efforts.

(Photo: http://www.newscom.com/cgi-bin/prnh/20080903/CLW042 )

Recent surveys demonstrate the importance of growing awareness of high blood pressure throughout the region:

   -- During the first 6 months of 2008, Centra Care Urgent Care measured the      Blood Pressures of nearly 50,000 adult patients. 71% had Hypertension      or Pre-Hypertension(1)    -- 80% of respondents in an independent survey did not know that normal      blood pressure is below 120/80(2)    

“Our data shows that Central Florida has a Blood Pressure problem,” said Scott Brady, MD, president/senior medical director of Centra Care Urgent Care, who serves as Medical Advisor to the Project Pressure campaign. “Elevated blood pressure is damaging arteries every day — putting people at increased risk for Stroke, Heart Attack, Aneurysm or some other medical catastrophe. It is a dangerous health condition, but it can be easily managed.”

As one of the most extensive community programs of its kind — involving cities, counties, corporations and the medical community — Project Pressure aims to increase Blood Pressure Awareness and Blood Pressure Health Compliance through a sustained and motivating multi-county educational campaign. It is the largest, most comprehensive health program ever implemented by Get Healthy Florida. Already dozens of participants have joined in an effort to engage the entire community in Project Pressure, including more than fifty fire stations and over a hundred physicians who will be screening residents for blood pressure.

Representing Central Florida’s largest employer, Walt Disney World Resort President Meg Crofton, with Nurse Minnie by her side, stressed the commitment the organization has to the health of their Cast Members and the community. “We are encouraging our community and our Cast Members to make one simple step toward a healthier lifestyle by rolling up their sleeves and getting their blood pressure checked. Health care and the wellness of employees and their families is one of the most important issues that companies face today. Project Pressure will complement the many resources we are providing Cast Members to help them live healthier lives,” said Crofton.

Project partners and participants include: Centra Care/Florida Hospital Urgent Care, Novartis Pharmaceuticals, Omron, Orange County, the City of Orlando, other municipalities and city and county government agencies, physicians, academic institutions, community-based organizations, media, health organizations and corporations.

Those interested in learning more about Project Pressure can visit http://www.projectpressure.com/ or call Get Healthy Florida at 407-688-8715.

About Project Pressure

Project Pressure will reach residents where they live and work through exciting events, blood pressure challenges, Fire Station Street Parties, BP tracking digital billboard, the chance to win prizes from an ambush-style Pressure Patrol Prize Van, and much more. There will be an interactive website where people can enter their BP numbers, learn lifestyle modification options such as healthy recipes, exercise tips and relaxation podcasts. The Project will conclude with a free Grand Finale community concert event.

Partners & Participants

Project Pressure is made possible thanks in part to: Florida Hospital Centra Care, Novartis Pharmaceuticals and Omron. Community Partners and participants already include: Orange County, the City of Orlando, the City of Winter Park, the City of Maitland, Orange County Public Schools, Orange County Fire Rescue, Orlando Fire Department, Maitland Fire Department, Winter Park Fire Department, Osceola County, the City of Kissimmee, City of Altamonte, Seminole County Public Schools, Florida Hospital, Walt Disney World, the University of Central Florida, Valencia Community College, LYNX, Darden Orlando, AAA, Central Florida YMCA, Florida Radiology Imaging, Florida Physicians Medical Group (FPMG), Physicians Associates, Carl Black Orlando, The Islands of the Bahamas, Brain Ready and HowStuffWorks.com , the Web site famous for its easy-to-understand explanations of how the world actually works, is a Project Pressure content partner, providing projectpressure.com with podcasts developed specifically for this initiative and articles, diagrams and videos that make it easy to understand “High Blood Pressure In-Depth.”

   About High Blood Pressure   What is Hypertension?  

High Blood Pressure, also known as Hypertension, has been called the “Silent Killer” because typically there are no signs. Normal blood pressure is less than 120/80 — anything higher than 140/90 is called Hypertension.

Why is Hypertension Bad?

High Blood Pressure can cause many problems including heart attack, stroke, kidney disease, aneurysm and heart failure. Bringing blood pressure back to normal range can prevent many of these dangerous problems. Every additional 20/10 increase in blood pressure DOUBLES the risk of death from heart attack or stroke.

   -- About 73 million people in the United States age 20 and older have high      blood pressure.   -- High blood pressure is a factor in 67% of heart attacks and 77% of      strokes in the U.S.   -- One in three Americans either has, or will have high blood pressure in      their lifetime.   -- Risk of death from heart attack or stroke DOUBLES w/each 20/10mm Hg      increase in BP.   -- 28 million sick days are taken each year due to BP   -- High BP and its complications cost the U.S. economy more than $100      billion each year    *U.S. Centers for Disease Control & American Heart Association     (1) During the first 6 months of 2008, Centra Care Urgent Care measured       the Blood Pressures of nearly 50,000 adult patients. 71% had       Hypertension or Pre-Hypertension.        Normal Blood Pressure is less than 120/80.  Anything over 120 systolic       or 80 diastolic is considered abnormal, and has a negative impact on       your health. Every age group (30s thru 90s) included patients whose       blood pressures were Dangerously High.  In fact, every age group had       patients with either Pre-hypertension or Hypertension requiring       medication.  The Highest systolic Blood Pressure of all age groups was       237 (which is a hypertension emergency).        In each age group, the average of all blood pressures (includes low       and normal readings) was higher than what is considered Normal blood       pressure.  For example, the average blood pressure of folks in their       30s was 124/80 ...  which is in the pre-hypertension range and       requires aggressive diet and lifestyle changes to prevent eminent       development of high blood pressure.        In addition, the patients were reviewed to see if there was any       correlation with race.  In fact, Centra Care statistics showed that       African-American patient's blood pressures averaged about 6 to 10       points higher than either White or Hispanic; with Hispanic averaging       about 2 points higher than Whites.    (2) In a recent, independent survey of 1,400 Central Floridians:      -- Of those respondents that have been told their blood pressure was        high -- only 21% say they are doing all they can to keep their        numbers low.     -- 80% of those surveyed did not know that normal blood pressure meant        below 120/80.     -- 46% said they thought hypertension was something that just came and        went throughout life     -- 1/3 of people who have been put on BP lowering medication by their        doctor said they either never take it or seldom take it as        prescribed.     About Get Healthy Florida  

Get Healthy Florida is an educational & event-based marketing organization committed to improving the health of people across the state of Florida. We create relevant health education and unique marketing opportunities through exciting health events that make a POSITIVE IMPACT on the community. Our organization began in 2001 and is already a recognized leader in the social marketing arena. For more information visit http://www.gethealthyflorida.com/

About Centra Care/Florida Hospital Urgent Care

For 25 years, Centra Care has provided adults and children preeminent medical care for non-life threatening illness and injury. Each of the 17 Central Florida locations is staffed by a Florida Hospital, board-certified physician and is equipped to handle X-Rays and labs on-site. Centra Care is Florida’s largest urgent care provider and Central Florida’s only urgent care facility backed by a nationally recognized health system. For more information visit http://www.centracare.org/

Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20080903/CLW042AP Archive: http://photoarchive.ap.org/AP PhotoExpress Network: PRN24PRN Photo Desk, [email protected]

Get Healthy Florida

CONTACT: Fawn Porter, Get Healthy Florida, +1-407-688-8715, or cell, +1-407-832-0620

Web site: http://www.projectpressure.com/http://www.gethealthyflorida.com/http://www.centracare.org/

Today Spoken Translation, Inc. and Bayshore Community Hospital announced that Bayshore will be the first hospital in the nation to adopt Spoken Translation’s product Converser for Healthcare, English/Spanish.

Converser is the world’s first interactive software system for reliable interpretation of wide-ranging conversations between English and Spanish speakers. Bayshore plans to use Converser in all customer-facing departments, aiming for one hundred percent patient satisfaction for its Spanish-speaking community. The hospital plans to introduce Converser into several departments initially and envisions that the entire staff will be able to use Converser within six months.

“We are very excited to be the first in the nation to begin using this innovative approach to interpreting,” said Bayshore Community Health Services President/CEO Raimonda Clark. “When used along with human interpreters, we think that Spoken Translation’s solution will help us to provide one hundred percent interpretation, 24/7/365. We are committed to providing the highest quality patient care for everyone in our community.” Dr. Mark Seligman, President and Founder of Spoken Translation, said, “We are happy that we can provide a reliable, constantly available, and extremely cost-effective product that will help Bayshore provide linguistically and culturally appropriate services to its Spanish-speaking community.”

During the beta-test period of Converser at Bayshore, the Director of Customer Service was urgently called to assist a Latino patient who did not speak English. The staff had been repeatedly instructing him — in English — to get into a wheelchair to go to the Radiology department for testing. The patient adamantly refused.

Newly equipped with Converser, the Director of Customer Service sat at the patient’s bedside and calmly typed into the program, “Sir, you need to go to Radiology for a chest x-ray now. A staff member will take you to the department in this wheelchair. Do you understand?” The patient was pleasantly surprised to hear the Spanish translation, as pronounced by the software’s speech technology. The spoken translation was played for him a second time — at which point he smiled, nodded yes, got into the wheelchair, and went off to Radiology.

“It is wonderful what we can accomplish when we all speak the same language,” remarked Wendy Brown, Vice President, Patient Care Services at Bayshore. “Converser made an important difference for this patient as well as for the staff.”

Bayshore Community Hospital has become the first healthcare institution to launch an organization-wide adoption of Converser for Healthcare. Bayshore is leveraging Converser’s ability to reliably translate almost any conversational sentence to contribute to its mission of providing excellence in healthcare.

Unlike electronic dictionaries or other communication tools, Converser for Healthcare is not limited to the delivery of pre-programmed phrases. The system actually supports wide-ranging two-way conversations, so that healthcare staff can say whatever they need to say. Moreover, the translations are verifiable: Converser’s Reliable Retranslation(TM) technology provides a translation of the translation, so users can verify accuracy for themselves. And if a word has been translated with an incorrect meaning (for example “right” can mean “correct” or “right-sided”), Converser provides a list of the word’s other possible meanings for quick correction. Text for translation can be entered via typing, handwriting, point-and-click — even speech. Bilingual transcripts are retained for the record.

About Spoken Translation

Spoken Translation, Inc. (www.spokentranslation.com), headquartered in Berkeley, CA, creates ground-breaking solutions for automatic cross-lingual communication. Its mission is to enable wide-ranging conversations across language barriers by building intuitive software systems combining automatic translation, speech recognition, speech synthesis, and its own proprietary technology. Spoken Translation’s flagship commercial product, Converser for Healthcare, is the world’s first interactive software for reliable interpretation of wide-ranging conversations between English and Spanish speakers.

About Bayshore Community Hospital

Bayshore Community Hospital (www.bayshorehospital.org) is a 225-bed acute care hospital located on a beautiful 37-acre campus in Holmdel, New Jersey. Its diverse array of quality services includes Cardiac Catheterization, Cancer Care Services, Diagnostic Imaging, Medical/Surgical, Emergency, Laboratory and Transitional Care. Bayshore Community Hospital is affiliated with Robert Wood Johnson University Hospital, The Robert Wood Johnson Health Network and The Cancer Institute of New Jersey.

Bayshore Community Health Services is served by a staff of over 2,000 physicians, nurses and healthcare professionals dedicated to meeting and exceeding patient’s expectations. Bayshore’s mission is to provide high-quality and compassionate services and promote an environment of good health and well-being for the people of the community it serves. Whether it’s a surgical procedure, rehabilitation program, health education or screening, the Bayshore family of organizations is growing and changing. We’re changing, to change your life.

The hospital began in 1972 when a group of dedicated residents identified the need for improved healthcare for the residents of this area. Since then, the Bayshore family of healthcare organizations has flourished to include more than a dozen medically related facilities in Monmouth and Middlesex counties.

 Contact: Dina Moskowitz V.P. Marketing Spoken Translation, Inc. (510) 843-9900 Email Contact  Contact: Chris Domalewski V.P., Marketing & Community Relations (732) 739-5905 Email Contact

SOURCE: Spoken Translation, Inc.

More than one million pharmacy patients are now enrolled in Walgreens (NYSE:WAG)(NASDAQ:WAG) Prescription Savings Club, the retail pharmacy industry’s most comprehensive prescription discount plan. Each day, thousands of new members opt to take advantage of savings on more than 5,000 brand name and generic medications, including a 90-day supply of more than 400 generic medications for less than $1 per week.

The Prescription Savings Club spans every drug category with significant savings on some of the most commonly prescribed medications, including treatments for pain, asthma, blood pressure, cholesterol, diabetes and women’s health. The club also covers preventive and lifestyle drugs not covered under most insurance plans, such as weight management, smoking cessation, family planning and sexual health. Savings will vary depending on the current cash price in a given area on a given day.

The club, launched last fall, has seen steady growth, driven primarily by one-on-one pharmacist recommendations. In recent weeks, advertising and marketing support has bolstered stronger awareness of the plan, propelling enrollment well beyond the one-million-member marker.

“This plan continues to attract so many people because it truly hits the mark with its breadth of coverage addressing a wide array of prescription needs,” said Walgreens senior vice president of pharmacy services Kermit Crawford. “Add the convenience of 6,400 locations and the security of being able to use one pharmacy for every prescription and the decision to join the club is easy.”

One of the most important benefits of Walgreens Prescription Savings Club is that it allows patients to save on most, if not all, their medications at one pharmacy. Many patients are unaware of the safety risk involved with filling a generic at one pharmacy, an antibiotic at another and a brand name at a third. Using one pharmacy retailer allows pharmacists to screen more completely for dangerous drug interactions. Walgreens pharmacists can access a patient’s Walgreens prescription records no matter which location the patient uses.

Enrollment in the Prescription Savings Club is only $20 a year for an individual or $35 a year for families(1) – a cost many patients recoup with just one prescription filled under the plan. Anyone not enrolled in a publicly-funded health care program such as Medicare or Medicaid is eligible and no prior authorization is required.

Walgreens Prescription Savings Club also covers hundreds of pet medications for substantial savings compared to prices found at many veterinarian offices. In addition, club members receive a 10 percent reward on a wide assortment of Walgreens brand products from OTC medications, baby care and household items to consumables.

“We know a million members is just the beginning for this plan,” said Crawford. “In this economy, people aren’t just looking for low-cost alternatives – they’re searching for the best overall value. We’re offering patients a way to stretch their dollars without sacrificing safety, service or convenience.”

For a complete list of medications covered under the Prescription Savings Club, go to Walgreens.com/rxsavingsclub or visit your local Walgreens pharmacy.

Walgreens is the nation’s largest drugstore chain with fiscal 2007 sales of $53.8 billion. The company operates 6,443 drugstores in 49 states, the District of Columbia and Puerto Rico. Walgreens provides the most convenient access to consumer goods and cost-effective health care services in America through its retail drugstores, Walgreens Health Services division and Walgreens Health and Wellness division. Walgreens Health Services assists pharmacy patients and prescription drug and medical plans through Walgreens Health Initiatives Inc. (a pharmacy benefit manager), Walgreens Mail Service Inc., Walgreens Home Care Inc., Walgreens Specialty Pharmacy LLC and SeniorMed LLC (a pharmacy provider to long-term care facilities). Walgreens Health and Wellness division includes Take Care Health Systems, which is comprised of: Take Care Consumer Solutions, managers of 220 convenient care clinics at Walgreens drugstores, and Take Care Employer Solutions, managers of worksite-based health and wellness services at 355 employer campuses.

(1) This card does not constitute insurance. Membership fee of $20 per individual or $35 per family per year required. Persons enrolled in a publicly funded health care program are ineligible. Membership may be cancelled within 30 days of issue date. For complete terms and conditions, call 1-866-WCARD-12 (1-866-922-7312) or visit www.walgreens.com/wcard.

digiChart, Inc., headquartered in Nashville, Tennessee, announced today the shift of OB-GYN physician practices to digiChart’s electronic medical record (EMR) and practice management system. Practices of all sizes nationwide are choosing digiChart for its comprehensive, pre-built OB-GYN content that enables improved documentation and workflow as well as accurate coding for proper reimbursement and increased revenue.

 Multiple practices(a) nationwide recently selecting digiChart include:  Alexandria Healthcare for Women - Alexandria, LA Aster OB-GYN - New York, NY Biltmore Women's Health and Aesthetics - Phoenix AZ Deseret Peak Women's Center - Tooele, UT Horizons Women's Health - Henderson, NV Jacobo Q. Hohenstein, MD - McAllen, TX Mountain West Obstetrics and Gynecology - Tooele, UT Park City Gynecology, LLC - Park City, UT Women's Center of Beaumont, LLC - Beaumont, TX Women Physicians for Women's Health - Hayward, CA  (a) This list represents only a sampling of recent digiChart contracts. The above clients do not all use digiChart practice management software. 

digiChart client Kevin Waddell, MD, of Women’s Center of Beaumont, LLC in Beaumont, Texas said, “Our goal is to be the premier OB-GYN practice in our area by utilizing the latest technology and enhancing patients’ experience while providing the highest standards of care. By utilizing digiChart, our practice operates more efficiently, and I have unlimited access to complete patient information when and where I need it. Most businesses today, large or small, use technology to manage complex and voluminous amounts of information to improve workflow, profitability and customer satisfaction. Physician practices need not be the exception and should take advantage of the tools available that assist in providing even better care to their patients.”

digiChart OB-GYN is a clinically superior OB-GYN-specific electronic medical record that enables consistent and accurate documentation of patient encounters which drives proper reimbursement for services provided and reduces risks to physicians and patients. digiChart includes an integrated, licensed American College of Obstetrics and Gynecology (ACOG) Antepartum Record within the electronic medical record and allows comprehensive documentation across the continuum of care for obstetrics patients. A web-native product, digiChart OB-GYN is accessible from anywhere in the world, 24 hours a day, allowing physicians to remain in control of patient care whether at home, the hospital or abroad. With its data driven design, data entry is consistent and streamlined and extensive reporting options are available to allow greater transparency into patient and financial outcomes.

“Physician practices often delay the purchase and implementation of an electronic medical record and practice management system, because of the financial and operational disruption they believe it will cause in the practice. Use of digiChart offers the opportunity to increase revenues and decrease overhead costs for OB-GYN practices. We minimize disruption during the implementation process by offering a user friendly application that eliminates template building and complicated server installation and maintenance,” commented G. William Bates, MD, President and Chief Executive Officer, digiChart, Inc. “The strength of digiChart is in our specialty focus and the breadth and depth of OB-GYN content provided to the practice on day one.”

For more information about digiChart, contact [email protected] or call 1-877-634-2727.

About digiChart, Inc.

Based in Nashville, TN, digiChart, Inc. is a leader in healthcare information technology solutions and services. Dedicated to improving women’s healthcare information management, digiChart provides Electronic Medical Record (EMR) and Practice Management System (PMS) solutions to OB-GYN practices across the country. Managing more than 600,000 individual patient records for gynecology and 93,000 active pregnancies, digiChart is the premier specialty- specific electronic medical record for OB-GYNs. digiChart is the winner of the 2007 and 2008 Microsoft HUG Innovation Award. digiChart OB-GYN version 7.0 is a CCHIT Certified(R) product for Clinical Records- Ambulatory – 2007. For more information, visit www.digichart.com.

Hansen Medical, Inc. (NASDAQ: HNSN), the global leader in flexible robotics and the developer of robotic technology for accurate 3D control of catheter movement, announced today that a team of physicians led by Professor Nick Cheshire at St. Mary’s Hospital, part of the Imperial College Healthcare NHS Trust, in London, England, utilized Hansen Medical’s Sensei(TM) Robotic Catheter System and Artisan(TM) Control Catheter to aid deployment of stent grafts used to treat an abdominal aortic aneurysm in a 78-year old patient. This procedure is believed to be the world’s first in which any robotic medical technology has been used to repair an aortic aneurysm through a patient’s vascular system.

“We have always believed vascular surgery would provide a very natural application for our Sensei and Artisan robotic technology, and the recent advancement at St. Mary’s Hospital demonstrates what is already within reach for our technology in this field,” said Fred Moll, M.D., co-founder and Chief Executive Officer of Hansen Medical. “Just as important, the recent experience of clinicians at St. Mary’s Hospital clearly demonstrates what physicians can accomplish when they use Hansen Medical’s advanced technology to provide more precise movement and control during different types of surgery.”

“The time taken to correctly position a stent graft during the treatment of an aneurysm is highly variable and depends on the complexity of the vascular anatomy,” explained Professor Nick Cheshire. “By providing increased catheter stability and accurate navigation, the Sensei system has the potential to greatly simplify the procedure and make it more predictable. In this case, it only took a few minutes to drive the Artisan catheter to the location where the stent was to be deployed.”

The aorta is the largest artery in the human body. An abdominal aortic aneurysm results from weakening and swelling of the artery’s walls, often as people age, and is frequently fatal if it ruptures. When positioned across the weakened section, stent grafts act as scaffolding that can help prevent the aneurysm from bursting. This surgery was performed through accessing the patient’s vascular system at the groin and using Hansen Medical’s Sensei system to accurately navigate the Artisan catheter up into the weakened section of the aorta, where the stent grafts were placed.

About Hansen Medical, Inc.

Hansen Medical, Inc., based in Mountain View, Calif., develops products and technology using robotics for the accurate positioning, manipulation and control of catheters and catheter-based technologies. Its first product, the Sensei Robotic Catheter system, is a robotic navigation system that enables clinicians to place mapping catheters in hard-to-reach anatomical locations within the heart easily, accurately and with stability during complex cardiac arrhythmia procedures. The Sensei system is compatible with fluoroscopy, ultrasound, 3D surface map and patient electrocardiogram data and was cleared by the U.S. Food and Drug Administration (FDA) in May 2007 for manipulation and control of certain mapping catheters in Electrophysiology (EP) procedures. The safety and effectiveness of the Sensei system for use with cardiac ablation catheters in the treatment of cardiac arrhythmias, including atrial fibrillation, and for use in the treatment of any type of vascular disease, have not been established in the United States. In the European Union, the Sensei system and Artisan catheter are intended to facilitate medical procedures within the atria of the heart using percutaneous catheters introduced through the vascular system. Additional information can be found at www.hansenmedical.com.

Hansen Medical technology was recognized in March 2008 by Frost & Sullivan, and presented with the consulting company’s 2008 Product Innovation Award in the field of U.S. Image-Guided and Robotic-Assisted Surgery Devices.

About Imperial College Healthcare NHS Trust

The Imperial College Healthcare NHS Trust comprises Charing Cross, Hammersmith Hospital, Queen Charlotte’s & Chelsea, St. Mary’s and Western Eye hospitals in London, England. It is the largest Trust in the UK, and in partnership with Imperial College London, is the UK’s first Academic Health Science Centre (AHSC). The AHSC was created to take the research discoveries it makes and translate them into new and improved treatments and techniques to directly benefit patients throughout the Trust, the NHS and the rest of the world.

The Vascular Unit at St. Mary’s Hospital in London is a leading European center for endovascular treatment with the largest number of endovascular thoracoabdominal aneurysm repairs worldwide. The Imperial College Endovascular Group has undertaken prize winning research into vascular robotics and won the 1st prize (scientific session) from the British Society of Endovascular Therapy in July 2008 (Riga CV, Bicknell CD, Hamady M, Cheshire NJW). For more details please visit www.imperial.nhs.uk.

Forward-Looking Statements

This press release contains forward-looking statements regarding, among other things, statements relating to expectations, goals, plans, objectives and future events. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Exchange Act and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements about possible future applications of the company’s technology in vascular surgery and the potential benefits of the company’s technology in new applications. These statements are based on the current estimates and assumptions of our management as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause actual results to differ materially from those indicated by forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, the risks and uncertainties inherent in our business, including potential safety and regulatory issues that could slow or suspend our development of new products and applications; our ability to manage growth and focus on selected new applications; the scope and validity of intellectual property rights applicable to our products; competition from other companies; and our ability to obtain additional financing to support our operations. These and other risks are described in greater detail under the heading “Risk Factors” contained in our periodic SEC filings, including our Quarterly Report on Form 10-Q filed with the SEC on August 5, 2008. Given these uncertainties, you should not place undue reliance on these forward-looking statements. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available.

Hansen Medical, Sensei, and Artisan, as well as the company’s heart design logo in use by itself or in combination with Hansen Medical, are trademarks or registered trademarks of Hansen Medical, Inc.

 Media Contact: Amy Cook 925.552.7893 Email Contact  Investor Contacts: Steven Van Dick 650.404.5800 Email Contact  At the Financial Relations Board: Lasse Glassen 213.486.6546 Email Contact

SOURCE: Hansen Medical, Inc.

HEALTH chiefs in the North West are to highlight how to recognise the signs that people may be suicidal and to show what help is availale to anyone thinking of taking their own life.

The Western Health and Social Services Trust (Western Trust) is marking World Suicide Prevention Day on September 10 by holding a public seminar in the South West College, Omagh for families bereaved through suicide.

The seminar will include a keynote presentation from Dr Frank Campbell, a world-wide renowned clinical social worker from The Crisis Centre Foundation in Baton Rouge, Louisiana, USA.

Dr Campbell will be delivering a powerful presentation called ‘The Canyon of Why’, which makes use of metaphors to aid healing from sudden and traumatic loss.

Dr Campbell said: “The question ‘why’, is one that persists for those bereaved by suicide. This presentation will illustrate the journey for the bereaved in attempting to find the answer.”

The Western Trust has recognised that suicide affects everyone and there is a shared responsibility to prevent it.

Recognising the need for community engagement, the Western Trust and Western Health and Social Services Board (WHSSB) are facilitating additional public events throughout the autumn.

Events will be providing practical advice and support for staff as well as community commitment for suicide prevention through the development of Community Response Plans.

On October 10, World Mental Health Day, a public conference will be considering the support required to help young people cope with life.

Barry McGale, suicide liaison officer for the Western Trust said: “The loss of life by suicide is a tragedy that devastates families.

“It sends ripples through communities and affects so many people and leaves the question ‘Why’?

“People self-harming may have emotional health problems, but only a minority of them seek professional help.

“The message is clear – a greater public awareness of the issues surrounding self harm and suicide and of the warning signs among our young can alert people to get the help that is needed earlier.”

Dorothy Hutchinson, chair of the Western Suicide Strategy Implementation Group, Western Health & Social Services Board said: “The Western Health & Social Services Board recognises that suicide is a hugely complex issue requiring a comprehensive solution with the help of the entire community.

“We are greatly concerned that a growing number of people are responding to life’s difficulties by self-harming and taking their life by suicide.

“As a result we wish to play an active role in working with a broad range of service providers to combat the problem and in recognising the important role the entire community plays.”

This seminar is free of charge and will be held in Omagh College at 7pm. For further details contact the Western Trust Health Promotion Department on 028 7186 5127.

(c) 2008 Belfast Telegraph. Provided by ProQuest LLC. All rights Reserved.

PRINCETON, N.J., Sept. 3 /PRNewswire-FirstCall/ — Derma Sciences, Inc. (BULLETIN BOARD: DSCI) announced that it will begin to sell its novel MOBILITY1(TM) Intermittent Pneumatic Compression Therapy device beginning in October after initially introducing the product to vascular surgeons at the 9th Annual New Cardiovascular Horizons (NCVH) Conference, scheduled September 10-13, 2008 in New Orleans. The patented device, licensed from Israeli technology company C-Boot in December 2006, is indicated for the treatment of chronic venous insufficiency, venous leg ulcers, lymphadema, the prevention of deep vein thrombosis, and numerous other indications. The product will be the only one of its kind, allowing mobile patients to receive optimal therapy while maintaining their lifestyle, as opposed to being homebound for treatment.

Derma Sciences CEO Ed Quilty stated, “This is another significant milestone for Derma as we continue to launch novel and important new technologies into the advanced wound care market. We’re excited about the launch of MOBILITY1 for several reasons: First, it is the only product of its kind and clearly will answer an unmet need among mobile patients who do not receive good outcomes from traditional static compression products like stockings and compression wraps. Allowing these patients to continue on with their normal lifestyle, getting them back to work sooner than later, will be a significant advantage over other pneumatic devices. Secondly, with its unparalleled ease of use, we believe that it will help to increase patient compliance, which is a huge issue with compression stockings, wraps, and other pneumatic devices. This should help drive efficacy, and potentially reduce the number of active leg ulcers and complications associated with these ulcers. Finally, we are excited to add another significant new product into our line, now that our sales force is up and running with our successful launch of MEDIHONEY(TM). This represents another step in the implementation of our strategic plan to drive shareholder value through the launch of novel, higher margin technologies.”

Compression therapy is broadly considered the standard of care for venous leg ulcers. Typically, patients will first receive inexpensive compression stocking and wraps, with outcomes measured over a six-month timeframe. Compliance is a significant issue with these types of products, as they are difficult for patients to apply, and can be painful. These products deliver what is known as “static” compression, as the level of compression remains consistent and does not change over time. Even with good compliance, usage of these products leads to a roughly 50 – 70% heal rate. For those patients who do not see good outcomes, the next course of action is the usage of an intermittent pneumatic compression device. This type of product delivers what is known as “dynamic” compression, where the compression first is applied at the heel, and then gradually progresses up the patient’s leg, helping to better move blood back to the heart. Although this dynamic compression is considered more optimal for those who do not heal with static compression, the compressors driving the system are quite large, necessitating the patients to remain at home while receiving therapy several times per day.

MOBILITY1 is based on two patents that allow the compressed air to be driven by the kinetic energy of the patient (while in motion). This allows the patient to keep their typical lifestyle, working, travelling, or simply getting around outdoors. The device also comes with a small compressor that can be used while the patient is at rest. The compressor itself is small enough to fit into a purse, briefcase, or travel bag, thus adding to the portability and mobility provided by the device.

Roughly 7 million people in the US suffer from Chronic Venous Insufficiency, and there are about 4 million leg ulcers in the US per year, with 85% of those resulting from vascular related issues. It has been estimated that the costs of care in the US for venous leg ulcers exceed $1 billion. Currently, static compression products such as stockings and wraps account for about $135 million, and stationary pneumatic compression devices account for $35 million.

About Derma Sciences

Derma Sciences is a global manufacturer and marketer of advanced wound-care products. Its key product, MEDIHONEY, is sold throughout the world by Derma Sciences and Comvita New Zealand — the licensor of the patented honey-based technology — and is the leading brand of honey-based dressings for the management of wounds and burns. The product has been shown to be effective in a variety of wounds and burns, and was recently the focus of a large-scale randomized controlled trial on leg ulcers. Derma has two products in development: the BIOGUARD(TM) line of barrier gauze dressings, and DSC127, the company’s novel angiotensin analog for accelerated wound healing and scar reduction. The barrier technology was licensed from Quick-Med in Q1 of 2007 and is pending its initial FDA marketing clearance. DSC127 was licensed from The University of Southern California in Q4 of 2007 and is entering into a Phase II study, with anticipated initial patient enrollment to begin in Q3 of 2008. For more information about Derma Sciences, Inc., visit its home page on the Internet at http://www.dermasciences.com/.

About New Cardiovascular Horizons

The 9th Annual New Cardiovascular Horizons (NCVH) Conference, scheduled September 10-13, 2008 in New Orleans, is the fourth largest cardiovascular conference in the nation. NCVH is the largest multidisciplinary conference to bring together cardiologists, fellows, residents, imaging professionals, surgeons, interventional radiologists, podiatrists, wound care specialists, cath lab techs, nurses, technologists, physician assistants, endocrinologists, family practice physicians, internal medicine specialists, pharmacists, EMTs, diabetologists, pharmacologists and vascular medicine specialists. Each year, the conference brings 3,500+ attendees, 125+ exhibitors , 180+ faculty and 200+ scientific presentations. The conference features live satellite broadcasts of interventional cases. A panel of renowned physicians narrates and discusses the cases during educational sessions, as they are viewed on wide screen by attendees. This dynamic teaching approach allows participants to experience decision making and procedures in real time. For more information about the New Cardiovascular Horizons Conference, visit its home page on the Internet at http://www.newcvhorizons.com/site.php.

    Contact:   Derma Sciences, Inc.         Allen & Caron Inc               Edward J. Quilty             Rudy Barrio (US Investors)               Chairman and CEO             [email protected]               [email protected]               (609) 514-4744               Brian Kennedy (media)                                            [email protected]                                            (212) 691-8087  

Derma Sciences, Inc.

CONTACT: Edward J. Quilty, Chairman and CEO of Derma Sciences, Inc.,+1-609-514-4744, [email protected]; or US Investors, Rudy Barrio,[email protected], or media, Brian Kennedy, +1-212-691-8087,[email protected], both of Allen & Caron Inc, for Derma Sciences, Inc.

Web site: http://www.dermasciences.com/

NEW YORK, Sept. 3 /PRNewswire/ — Exosome Diagnostics, Inc. today announced additions to its management team as the company moves forward with development of its blood-based diagnostics that can identify cancer-specific genetic mutations.

Wayne D. Comper, Ph.D., D.Sc., has joined Exosome Diagnostics as the chief scientific officer. Dr. Comper has extensive experience both as a biotechnology executive and as a biomedical research scientist. Prior to joining Exosome, he was chief science officer of AusAm Biotechnologies, Inc., a company developing diagnostics and therapeutics to identify and treat kidney, cardiovascular and infectious diseases. Dr. Comper has also published over 160 articles in peer-reviewed international journals. Dr. Comper received both his Ph.D. and D.Sc. from Monash University, Clayton, Victoria, Australia.

Tom Tsakeris has been appointed director of regulatory affairs. Mr. Tsakeris’ expertise includes extensive experience with the Food and Drug Administration (FDA) and as an advisor to companies on the regulatory approval process. Prior to joining Exosome, Mr. Tsakeris was president of Devices and Diagnostics Consulting Group, Inc. His prior positions also include director of the Division of Clinical Laboratory Devices, Office of Device Evaluation, Center for Devices and Radiological Health and several other management roles at FDA. During his tenure at FDA, he played a key role in developing the implementation strategy for the Clinical Laboratory Improvement Act (CLIA) of 1988.

“With our exosome technology, we are able to overcome a fundamental issue of how to capture diagnostic quantities of genetic mutations in blood,” said James McCullough, chairman & chief executive officer. “These mutations contain enormous amounts of information specific to different types of cancers that can be used for diagnosis and disease monitoring. These important management additions will now enable us to expand clinical development of our first blood-based genomic test for neuroblastoma, complete a partnership with a CLIA-approved clinical laboratory and launch of our first clinical diagnostic in 2009.”

About Exosome Diagnostics

Exosome Diagnostics is a developer of proprietary genetics-based diagnostic tests with applications in oncology and endocrinology. Exosome’s core technology is based on the discovery that circulating nanovesicles called exosomes contain unique genetic markers and that they can be reliably harvested and used as a diagnostic tool for cancers and metabolic diseases. Exosome Diagnostics’ lead program is a blood-based diagnostic test for the management of neuroblastoma patients. For more information, visit http://www.exosomedx.com/.

    Media Contacts:    Robert Flamm, Ph.D., or David Schull    Russo Partners    (212) 845-4226    [email protected]    [email protected]  

Exosome Diagnostics, Inc.

CONTACT: Robert Flamm, Ph.D., [email protected], orDavid Schull, [email protected], both of Russo Partners,+1-212-845-4226

Web site: http://www.exosomedx.com/

BETHEL, Conn., Sept. 3 /PRNewswire-FirstCall/ — Aduromed Industries, Inc. (BULLETIN BOARD: ADRM) , a provider of innovative technology and services for the onsite treatment and disposal of regulated medical waste, today announced the appointment of Mr. Scott Grisanti as President and Chief Executive Officer of the Company. Mr. Grisanti was also elected as a director of the Company. The Company also announced the raising of an additional $1 million of new equity capital pursuant to its previously announced corporate restructuring. This brings the total amount of new equity capital raised pursuant to the restructuring to $4.8 million after placement fees.

Prior to joining the Company, Mr. Grisanti was the Executive Vice President of Sales, Marketing and Services at Primavera Systems, Inc., a leading provider of program and portfolio management application software and services solutions used to manage large capital projects in targeted market segments. He led the effort to increase revenues from $108 million to $205 million projected for 2008. Prior to joining Primavera, Grisanti served as Executive Vice President and Chief Marketing Officer for eResearchTechnology, Inc., a leading provider of technology and services for the new drug development industry. Responsible for global sales, marketing and strategic alliances, he was a key member of an executive team that increased revenues from $28 million to $109 million and market capitalization from $42 million to $1.5 billion. Previously, Grisanti served in an executive sales management capacity at supply chain execution application solution providers ClearCross, Inc. and Optum, Inc. He received his bachelor degree in English and Journalism from Rutgers University, where he was elected to Phi Beta Kappa.

Mr. Joseph Esposito, Chairman of the Company, commented, “I have known and worked with Scott for many years and I am confident that Scott brings exceptional leadership experience to the executive management team and the board. He possesses a unique blend of business development skills and operational experience that will enable him to execute the Company’s plan to accelerate growth at this stage in its development. I welcome Scott to the Aduromed team and look forward to once again working with him.”

“I am excited to have the opportunity to again partner with Joe, as well as the entire Aduromed team, to create significant shareholder value as we execute our plan to accelerate growth at Aduromed,” said Mr. Grisanti. “My immediate focus will be to expand the product line, offering standard systems with flexible acquisition alternatives to a broader base of potential clients. In addition, we will be adding talent to the management team to enable us to expand our regulatory service business and expand our market footprint through complementary channels of distribution.”

About Aduromed

Aduromed Industries, Inc., through its wholly-owned subsidiary, Aduromed Corporation, is a provider of innovative technology and services for the onsite treatment and disposal of regulated medical waste. Aduromed’s flagship MedClean(R) Series systems are fully integrated, turnkey technology solutions that enable hospitals and other healthcare providers to safely, efficiently and cost-effectively convert bio-hazardous regulated medical waste into sterile, unrecognizable material suitable for disposal as municipal solid waste.

Aduromed was founded in 1997 with corporate headquarters, research and development and distribution facilities located in Bethel, Connecticut. Further information on Aduromed can be found at http://www.aduromed.com/ and in filings with the Securities and Exchange Commission found at http://www.sec.gov/.

Statements about our future expectations are “forward-looking statements” within the meaning of applicable Federal Securities Laws, and are not guarantees of future performance. When used herein, the words “may,””will,””should,””anticipate,””believe,””appear,””intend,””plan,””expect,””estimate,””approximate,” and similar expressions are intended to identify such forward-looking statements. These statements involve risks and uncertainties inherent in our business, including those set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2007, filed with the SEC on March 31, 2008, and other filings with the SEC, and are subject to change at any time. Our actual results could differ materially from these forward-looking statements. We undertake no obligation to update publicly any forward-looking statement.

Aduromed Industries, Inc.

CONTACT: Kevin Dunphy, Chief Financial Officer of Aduromed Industries,Inc., +1-203-798-1080, [email protected]; or Investors, Cameron Donahue ofHayden Communications, Inc., +1-651-653-1854, [email protected], forAduromed Industries, Inc.

Web site: http://www.aduromed.com/

Plexxikon Inc. today announced that it has initiated a Phase 1 human clinical trial for PLX5568, a novel kinase inhibitor targeted for the treatment of at least two major indications with unmet medical needs: pain as well as polycystic kidney disease (PKD). PLX5568 has demonstrated robust preclinical efficacy in multiple pain models, including neuropathic pain as well as acute and inflammatory pain. In addition, PLX5568 has demonstrated compelling efficacy in multiple preclinical models of PKD.

Dosing has been completed in the first cohort of healthy volunteer subjects in the single ascending dose, double-blind, placebo-controlled trial, which will enroll approximately 30 subjects. This study will be followed by a multiple ascending dose, double-blind, placebo-controlled trial, which will enroll approximately 32 healthy volunteer subjects. Together, these studies are being conducted to evaluate the safety and tolerability of PLX5568 as well as to gain insight into the pharmacokinetic profile of the drug candidate. Preliminary pharmacokinetic data from the Phase 1 trial indicate that the exposure in blood achieved with the initial dose is in the target range required to show efficacy with once-a-day capsule dosing.

“PLX5568 represents the fifth Investigational New Drug (IND) from our discovery platform to enter the clinic in four years, and expands our therapeutic portfolio now also to pain and renal disease with this first-in-class agent, underscoring our early development capabilities as well as the productivity and breadth of our discovery platform,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Additionally, PLX5568 is a highly selective drug candidate and yet another example of Plexxikon’s hallmark capability to design very selective kinase inhibitors. Given this capability, we are uniquely positioned to explore kinase drug candidates for the potential treatment of chronic indications where safety is paramount.”

PLX5568 is a very selective and potent kinase inhibitor. Non-clinical GLP toxicology studies which included doses up to 2000 mgs per day over a period of 28 days, have confirmed the attractive safety profile of our selective kinase inhibitor, and that such selectivity potentially confers safety to our drug candidate. Kinases represent a large family of potential drug targets through which a broad range of chronic diseases could be treated with safe and selective drugs that inhibit their activity.

About PLX5568 in Pain

PLX5568 is a first-in-class, oral, non-opioid agent with opiate-like efficacy, and a rapid onset of action. Kinases play a key role in the signaling pathways that control the sensation of pain and the transmission of pain sensing signals. Preclinical efficacy in various types of pain models demonstrated clear analgesic responses to treatment with PLX5568, comparable to gabapentin or morphine even at low doses of PLX5568, but without the side effects of an opiate. Following the successful completion of the Phase 1 trial, Plexxikon plans to initiate a Phase 2 clinical trial in neuropathic pain patients in 2009.

As a non-opioid and oral pain agent, PLX5568 could address significant unmet needs in chronic pain, cancer pain and neuropathic pain, addressing substantial markets with an estimated 7.8 million patients with neuropathic pain alone. There is a significant opportunity for novel pain treatments, since most currently available pain therapies suffer from suboptimal efficacy, intolerable side effects or long-term safety concerns, including sedation and addiction.

About PLX5568 in Polycystic Kidney Disease

PLX5568 has also demonstrated impressive efficacy in orthologous models of both forms of PKD, including effects on cyst size and renal function. Following the successful completion of the Phase 1 trial and chronic toxicology studies, Plexxikon plans to initiate a Phase 2 clinical trial in PKD patients in 2009.

PKD is a genetic disease in which cysts form in the kidneys, causing them to become enlarged and infected, or burst, ultimately leading to loss of kidney function. Currently, there are no treatments for this disease, and patients eventually progress to kidney transplant or dialysis. PKD is the most common life-threatening genetic disease, affecting approximately 600,000 patients in the U.S. and over 12 million patients worldwide.

Plexxikon Profile

Plexxikon is a leader in structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s clinical stage programs include PLX204 for the treatment of diabetes, PLX4032 for the treatment of melanoma and colorectal cancer and PLX5568 for the treatment of pain and renal disease. Among the company’s preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.

Plexxikon’s proprietary Scaffold-Based Drug Discovery(TM) platform is being applied to build a pipeline of diverse product opportunities for the treatment of metabolic and cardiovascular disease, inflammation, oncology and CNS disorders. This discovery process integrates a number of state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in multiple disease areas addressing significant unmet needs in each therapeutic category.

Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit www.plexxikon.com.

TEMPE, Ariz., Sept. 3, 2008 (GLOBE NEWSWIRE) — OrthoLogic Corp. (Nasdaq:OLGC) announced today the publication of positive results from a pre-clinical study of Chrysalin(r) (rusalatide acetate or TP508) in a model of chronic myocardial ischemia. The study demonstrates that Chrysalin significantly increases vascular perfusion and myocardial function in porcine hearts with induced chronic myocardial ischemia.

Cardiovascular disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention. A therapeutic agent that helps to restore blood flow and function to damaged cardiac tissue could represent an important clinical option in the treatment of chronic and acute heart disease.

Chrysalin-treated animals demonstrated statistically significant improvements compared to placebo in vascular perfusion (p less than 0.02), myocardial function (p less than 0.02) and nitric oxide (NO) mediated endothelial function in small arteries (p less than 0.05). The study was performed at Texas A&M University in the laboratory of Theresa W. Fossum, DVM, Ph.D.

The article also presents data showing that, at the molecular level in cultured human endothelial cells, Chrysalin upregulates endothelial nitric oxide synthase (eNOS) expression and stimulates eNOS activation, leading to increased production of NO. Diminished NO production by endothelial cells is associated with vascular disease and thrombotic events leading to organ failure.

The discovery that Chrysalin reverses endothelial dysfunction in hearts with chronic ischemia and stimulates NO production provides a compelling rationale to guide the development of Chrysalin treatment for vascular disorders.

The study results are published in the September 2008 edition of the Journal of Cardiovascular Pharmacology and Therapeutics (Volume 13, No. 3).

“We are pleased to announce these exciting pre-clinical data showing the effectiveness of Chrysalin in chronic myocardial ischemia,” said Randolph C. Steer, MD, Ph.D., President of OrthoLogic. “These important findings complement our ongoing pre-clinical studies of Chrysalin in acute myocardial ischemia and infarction, for which we announced preliminary results on August 7, 2008. Chrysalin has now demonstrated significant biological and clinical effects in models of both chronic and acute myocardial ischemia. Based on these results, we believe that Chrysalin could represent an exciting breakthrough for future treatment of heart disease.”

About OrthoLogic

OrthoLogic is a biotechnology company committed to developing a pipeline of novel therapeutic peptides aimed at helping patients with under-served medical conditions. The Company is focused on development and commercialization of two product platforms: AZX100 and Chrysalin(r) (rusalatide acetate or TP508).

AZX100 is a novel synthetic 24-amino acid peptide, one of a new class of compounds in the field of smooth muscle relaxation and fibrosis. Based on its demonstrated effects in pre-clinical models, AZX100 is currently being evaluated for commercially significant medical applications such as the treatment of pulmonary disease, the prevention of hypertrophic and keloid scarring and intimal hyperplasia. OrthoLogic has an exclusive worldwide license to AZX100.

Chrysalin, the Company’s novel synthetic 23-amino acid peptide, has been proven in multiple pre-clinical and clinical models to stimulate cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. It is currently being evaluated in disorders that involve vascular endothelial dysfunction, such as acute myocardial infarction and chronic myocardial ischemia. The Company owns exclusive worldwide rights to Chrysalin.

OrthoLogic’s corporate headquarters are in Tempe, Arizona. For more information, please visit the Company’s website: www.orthologic.com.

Statements in this press release or otherwise attributable to OrthoLogic regarding our business that are not historical facts are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, which include the timing and acceptability of FDA filings and the efficacy and marketability of potential products, involve risks and uncertainties that could cause actual results to differ materially from predicted results. These risks include: delays in obtaining or inability to obtain FDA, institutional review board or other regulatory approvals of pre-clinical or clinical testing; unfavorable outcomes in our pre-clinical and clinical testing; the development by others of competing technologies and therapeutics that may have greater efficacy or lower cost; delays in obtaining or inability to obtain FDA or other necessary regulatory approval of our products; our inability to successfully and cost effectively develop or outsource manufacturing and marketing of any products we are able to bring to market; changes in FDA or other regulations that affect our ability to obtain regulatory approval of our products, increase our manufacturing costs or limit our ability to market our product; affects on our stock price and liquidity if we are unable to meet the requirements for continued listing on the NASDAQ Global Market; our possible need for additional capital in the future to fund the continued development of our product candidates; and other factors discussed in our Form 10-K for the fiscal year ended December 31, 2007, and other documents we file with the Securities and Exchange Commission.

Editors’ Note: This press release is also available under the Investors section of the Company’s website at www.orthologic.com.

This news release was distributed by GlobeNewswire, www.globenewswire.com

 CONTACT: OrthoLogic Corp.          Investor Relations          Karen Struck          (602) 286-5250          [email protected]                    The Trout Group          Lauren Glaser          (415) 392-3310          [email protected] 

Thomas Weisel Partners (NASDAQ: TWPG) (TSX: TWP), a global growth-focused investment bank, will host its Annual Healthcare Conference, September 3-5 at the Four Seasons Hotel in Boston. Institutional investors and company management will gather for this three-day conference, which will focus on opportunities and challenges in the healthcare industry in 2008 and beyond.

The conference will showcase presentations from over 150 established and emerging public and private companies, including those engaged in biotechnology, diagnostics, healthcare information technology, pharmaceutical services, life science technology, medical devices and specialty pharmaceuticals.

“We remain committed to focused coverage of Healthcare, one of the most important areas of the U.S. economy. The Healthcare sector represents 13% of the S&P 500 Index, larger than any other sector except Financial Services, Energy and Information Technology. Healthcare stocks have significantly outperformed the overall market over the last year. Over the last 13 weeks, Healthcare stocks are up 6.1%, outperforming the overall market, which has fallen by a similar amount. We believe long-term healthcare demand trends remain positive,” said Keith Gay, Head of TWP’s Research Group.

The conference kicks off Wednesday morning and will be led by Thomas Weisel Partners seven senior health care research analysts: Donald Ellis, specialty pharmaceuticals; Steven Halper, healthcare information technology and pharmaceutical services; Raj Denhoy, medical devices; Peter Lawson, life science and diagnostics; Philip Legendy, medical devices; Ian Somaiya, biotechnology; and Stephen Willey, biotechnology. Analysts will offer insight into the major trends impacting their respective sectors.

A full list of company participants follows:

 ACADIA Pharmaceuticals Inc. Affymax, Inc. Affymetrix, Inc. Agilent Technologies, Inc. Alkermes, Inc. Allscripts Healthcare Solutions, Inc. American Medical Systems, Inc. AmerisourceBergen Corporation AMICAS, Inc. Amylin Pharmaceuticals, Inc. Archus Orthopedics, Inc. Array BioPharma Inc. Asuragen, Inc. athenahealth, Inc. AtriCure, Inc. Atritech, Inc. ATS Medical, Inc. Auxilium Pharmaceuticals, Inc. Beckman Coulter, Inc. Becton, Dickinson and Company Bio-Rad Laboratories, Inc. Biogen Idec Inc. CambridgeSoft Corporation CardioNet, Inc. Celera Corporation Celgene Corporation Cephalon, Inc. Cepheid Cerner Corporation CONMED Corporation Corcept Therapeutics Incorporated Covance Inc. Cubist Pharmaceuticals, Inc. CVS Caremark Corporation Cyberonics, Inc. dbMotion Ltd. deCODE genetics, Inc. Devax, Inc. Dionex Corporation Dyax Corp. eHealth, Inc. eResearchTechnology, Inc. Eurand (US) Exactech, Inc. Exelixis, Inc. Gen-Probe Incorporated Genentech, Inc. Genzyme Corporation Geron Corporation Gilead Sciences, Inc. GlobeImmune, Inc. Guava Technologies, Inc. HandyLab, Inc. Hansen Medical, Inc. Helicos BioSciences Corp. HMS Holdings Corp. Human Genome Sciences, Inc. iCAD, Inc. Idenix Pharmaceuticals, Inc. Illumina Inc. Immucor, Inc. ImmunoGen, Inc. IMS Health Incorporated Insulet Corporation Integra LifeSciences Corporation InterMune, Inc. Intuitive Surgical, Inc. ISIS Pharmaceuticals, Inc. ISTA Pharmaceuticals, Inc. King Pharmaceuticals, Inc. Ligand Pharmaceuticals Inc. Light Sciences Oncology Inc. Lincare Holdings Inc. Lumen Biomedical, Inc. Luminex Corporation Masimo Corporation McKesson Corporation Medarex, Inc. Medco Health Solutions, Inc. Medicis Merit Medical Systems, Inc. Mettler-Toledo International, Inc. Millipore Corporation Monogram Biosciences, Inc. Nanosphere, Inc. Natus Medical Incorporated NeoGuide Systems Neurocrine Biosciences, Inc. Neuronetics, Inc. Novadaq Technologies Inc. NuVasive, Inc. NxStage Medical, Inc. Obagi Medical Products, Inc. Omnicare, Inc. Omnicell, Inc. OmniGuide, Inc. Orthofix International N.V. Osiris Therapeutics, Inc. Owens & Minor, Inc. Paracor Medical, Inc. Paratek Pharmaceuticals, Inc. PAREXEL International Corporation Peplin, Inc. PerkinElmer, Inc. Pharmaceutical Product Development, Inc. Pharmaxis Ltd. Phase Forward Incorporated Picis, Inc. Poniard Pharmaceuticals Inc. Qiagen N.V. Reata Pharmaceuticals, Inc. Recoly NV Regulus Therapeutics LLC Rib-X Pharmaceuticals, Inc. Rigel Pharmaceuticals, Inc. ROXRO PHARMA, Inc. RTI Biologics Inc. Salix Pharmaceuticals, Ltd. Santarus, Inc. Seattle Genetics, Inc. Sepracor, Inc. Sequenom, Inc. SeraCare Life Sciences, Inc. Somaxon Pharmaceuticals, Inc. Stiefel Laboratories, Inc. Stryker Corporation superDimension, Inc. SXC Health Solutions Corporation Symmetry Medical, Inc. Symyx Technologies, Inc. Syneron Medical Ltd. T2 Biosystems, Inc. Targanta Therapeutics Corporation Teleflex Incorporated Theravance, Inc. Thermage, Inc. Thermo Fisher Scientific Inc. TomoTherapy Incorporated ULURU Inc. Varian, Inc. Varian Medical Systems, Inc. Vertex Pharmaceuticals Inc. ViroPharma Incorporated Vital Images, Inc. Volcano Corporation Walgreen Co. Wright Medical Group, Inc. Xoft Inc. Zimmer Holdings, Inc. Zogenix, Inc. 

Thomas Weisel Partners Group, Inc. is an investment bank, founded in 1998, focused principally on the growth sectors of the economy. Thomas Weisel Partners Group, Inc. generates revenues from three principal sources: investment banking, brokerage and asset management. The investment banking group is comprised of two disciplines: corporate finance and strategic advisory. The brokerage group provides equity and convertible debt securities sales and trading services to institutional investors, and offers brokerage, advisory and cash management services to high-net-worth individuals and corporate clients. The asset management group consists of: private equity, public equity and distribution management. Thomas Weisel Partners is headquartered in San Francisco with additional offices in Baltimore, Boston, Calgary, Chicago, Cleveland, Denver, New York, Portland, Silicon Valley, Toronto, London, Mumbai and Zurich. For more information, please visit www.tweisel.com.

SOURCE: Thomas Weisel Partners Group, Inc.

By Petrini, Carlo Gainotti, Sabina

Abstract First we give an overview of the historical development of public health. Then we present some public-health deontology codes and some ethical principles. We highlight difficulties in defining ethics for public health, with specific reference to three of them that concern: (i) the adaptability to public health of the classical principles of bioethics; (ii) the duty to respect and safeguard the individual while acting within the community perspective that is typical of public health; and (iii) the application-oriented nature of public health and the general lack of attention towards the ethical implications of collective interventions (compared with research). We then mention some proposals drafted from North American bioethics “principles” and utilitarian, liberal and communitarian views. Drawing from other approaches, personalism is outlined as being the theory that offers a consistent set of values and alternative principles that are relevant for public health.

Bulletin of the World Health Organization 2008;86:624-629.

(ProQuest: … denotes formula omitted.)

The past and present of public health

In developed countries, where high standards of living have been achieved, public health is often viewed as a sort of secular faith providing good advice (on nutrition, physical health, longevity, etc.) and imposing rules (wearing seatbelts, refraining from smoking in public places, etc.) for the protection of collective health. This moralizing vocation of public health has been much described in the literature.1 In this respect, the debate over information, persuasion, privacy and their ethical implications has also become much broader.2

These features of public health are a development of its secular functions, traditionally carried out by doctors (if public health is linked with the existence of registry data on births, marriages and deaths).3 Indeed, the main idea of public health, that implicitly crosses centuries of human history, can be summed up in a definition by Anne Fagot-Largeault: “a population in good health reproduces well, provides strong soldiers, good workers and fertile women”.4

Only in recent years has the concept of public health been widened to incorporate the idea of global health. The latter can be associated with the well-known definition of health by WHO.5 As a consequence, the role of public health that was previously limited to communicable disease control6 shifted to a broader-spectrum action that is more overt in developed countries. Today public health is primarily related to epidemiology7 but also to social, economical and political matters.8,9 The widening of public health’s scope (so broad as to engender some confusion), together with the rise of new emergencies in epidemiology,10 also led some scholars to reflect on the opportunity for public health to return to dealing mainly with communicable disease control, leaving other areas of intervention to other disciplines.11 However, the development of public health is by now a consolidated reality;12 this means that public health is located at a crowded intersection among risks, health effects and prevention.13

Codes of ethics and bioethics

Within such a broad framework of topics, anyone attempting to find unifying principles for public-health ethics might soon become discouraged. Rules of good conduct are quite easy to define in ethics. Transparency, equity and honesty can be mentioned, as well as other norms that are unanimously accepted in professional and ethical codes.14 However, public-health issues are hard to tackle with simple standards of behaviour: ethical foundations are also required as a basis for decision-making. Until recently, no relevant deontological suggestion or ethical code was available for public- health professionals. One of the most significant proposals of this kind is the American Public Health Association’s public-health code of ethics.15 Apart from in the United States of America, no other wide-ranging efforts have been made to outline codes for public- health ethics. The difficulty of defining the category of public- health professionals has contributed to this gap.

Beside professional codes, other codes and guidelines include general rules of conduct that are relevant for public health. For example, in 2007, David King put forward codes of practice that apply to all scientific circumstances:16

1. Act with skill and care in all scientific work. Maintain up- to-date skills and assist their development in others.

2. Take steps to prevent corrupt practices and professional misconduct. Declare conflicts of interest.

3. Be alert to the ways in which research derives from and affects the work of other people and respect the rights and reputations of others.

4. Ensure that your work is lawful and justified.

5. Minimize and justify any adverse effect your work may have on people, animals and the natural environment.

6. Seek to discuss the issues that science raises for society. Listen to the aspirations and concerns of others.

7. Do not knowingly mislead, or allow others to be misled, about scientific matters. Present and review scientific evidence, theory or interpretation honestly and accurately.

Standards for “good conduct” are surely important but rules of good behaviour alone cannot solve complex dilemmas. Conflicts among values often arise in public health, especially among the needs and rights of individuals as opposed to the collective need to protect health as a public asset. In these circumstances, deeper analysis must be performed in the search of principles to serve as reference. Proposals have been made to this aim. The best known document in Europe is that of the British Nuffield Council of Bioethics.17 Wide- ranging comparative surveys have been carried out on the approaches to public-health ethics in Member States of the European Union. Surveys have also been conducted as part of two projects financed by the European Commission including: Basic ethical principles in European bioethics and biolaw (1995-1998)18 and the more recent European Public Health Ethics Network – EuroPHEN (2003-2006).19

Ethical principles for public health

Three difficulties

Deontological rules can be applied to different areas, including public health, without much difficulty. However, studies show that greater problems are encountered when moving from the simple behavioural norm to its underlying ethical justification.18,19 Some inputs may be found in the traditional approaches of bioethics but problems do arise.20 Three main difficulties are outlined here in the definition of principles for public-health ethics.

First, one may wonder if the traditional bioethics principles (mainly focused on clinical aspects and on the doctor-patient relationship) can be adapted to public-health ethics or if new directions must be explored to this aim.21,22 The first option is supported by the idea that general ethical principles can be applied, with possible adjustments, to various circumstances.23 It should be noted, however, that environment-specific elements must be considered in implementing these principles.24

Second, the duty to safeguard individual rights must be respected, even if acting within a community perspective that is typical of public health.25

Third, public health has an application- oriented nature and applies to groups or populations. Definitions of public health in the literature clearly highlight its application-based character. According to a very popular definition: “public health is the procedure whereby local, national and international resources are mobilized and committed in order to make sure that people are in a position to live healthily”.26

Bioethicians usually pay attention to the ethical problems of human experimentation more than public-health interventions.27 However, as with research, public-health interventions carry ethical problems. One aspect of these interventions that often undergoes ethical-legal assessment is the protection of personal data.

Public-health research is mainly observational and, as such, does not often raise relevant problems. Nevertheless, public-health interventions involve acting at the individual level and have consequences for equality and justice.1 Moreover, there is a fine dividing line between public-health intervention and research: public-health interventions are almost always research activities in that they contribute to the increase of knowledge.28,29

In this respect, public-health intervention protocols may rightly undergo ethical evaluations on the part of ethics committees and it is not infrequent that the proponents of research want their protocols to be revised by a committee of experts. Still, in most countries, public-health research protocols are not assessed by ethics committees.

Principlism applied to public health

The term “principle” has a broad significance. According to the Encyclopedia of ethics it is defined as “a fundamental rule, law or doctrine, from which other rules or judgments are derived”.30 In bioethics the word “principle” has at least two main meanings, indicating opposite perspectives. The first meaning stands for the foundation of a theory, from which theories derive. The second means practical guideline for action: in this case “principle” derives from ethical theories.31 Often, if not otherwise stated, the term is used to refer to the well-known principles of North American bioethics (autonomy, beneficence, non-maleficence, justice).32 Ever since their formulation, these principles have been widely applied to the ethical analysis of health-care problems, often in conjunction with other principles or divided into subprinciples. Some authors have suggested the application of the principles to public-health ethics.30 However, they have proven inadequate in medical ethics33 and, all the more so, in public-health ethics where conflicts among values arise and value shortcomings are frequent.34 The main problem with the principles is that they often result in relativism. Indeed the principle of benevolence, to do good to others, does not indicate what “good” is and what is right for an individual. Autonomy stands for freedom of action but the concept implies that persons lacking autonomy wouldn’t be considered in certain situations. The concept of justice is similarly ambiguous: the principle does not define what is “just” and to what a person is entitled.

Philosophical theories are also applied to bioethics and public- health ethics. In public health, some positions are more common: positions based on outcomes (utilitarianism), positions focused on rights and opportunities (Kantian theories), views that emphasize sociality and solidarity (communitarianism).1 Utilitarianism asserts that decisions should be judged by their consequences, in particular by their effect on the total sum of individual wellbeing. Following this view, public-health policies must be aimed to produce “the greatest happiness of the greatest number”.35 This approach is very intuitive in public health but has some limitations. Difficulties arise for example in the measurement of wellbeing which can be defined with reference to an individual’s personal experiences or to more objective and measurable components, e.g. quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs).36 However, the most important critique to utilitarianism is grounded on the view that it easily leads to unfairness and to the sacrifice of individual rights and freedoms to warrant the public utility.37 Individual rights and freedoms are the main good to be preserved in Kantian theories. Kant argued that human beings ought to be treated with respect, as ends in themselves, not as means to another individual’s ends.38 This assertion has important consequences in public-health policies, but is not without ambiguities. Indeed two kinds of liberalism can be drawn: libertarians and egalitarians.39 Libertarians believe that only negative rights deserve protection to warrant individual freedom. By contrast, egalitarian liberals argue that the right to choice is meaningless without adequate resources. Respectively, the two perspectives entail a minimal or, vice versa, a strong state intervention for the sake of individual health.

Critics of utilitarianism and liberalism point out that these theories neglect the collective dimension of public- health ethics that is strongly valued in communitarianism. Communitarianism values highly the social dimension of health-care policies and involves visions of the appropriate social order and the virtues that will maintain such an order in a particular community. However, a basic question in communitarianism is: who decides what is virtuous? Every community could define its own norms or, by contrast, a single form of good society may serve as a reference for all communities. Ethics- of-care feminism can also be mentioned. Ethics-of-care proponents argue that real people live in families and real caring relationships are not impartial, impersonal or equal. Health-care policies must hence consider the factual dimension of caring, which is mostly carried out by women, and must be more supportive towards caring roles.39 All the outlined theories in our view may offer a contribution to a continuing discussion about how to deal ethically with public-health matters and how to organize society. What is missing in these theories is a clear definition of the concept and value of the human person: a primary point in personalism.

From traditional philosophy to personalism

Personalism may offer some compensation for the conflicts and shortcomings of principlism. For reasons of comprehensiveness, it might be useful here to mention its most elementary, and possibly obvious, aspects. Personalism should not be confused with individualism, which considers auto-decisions as the main (or only) constitutive feature of person. Personalism is based upon our common shared human nature. It takes as its primary ethical principle that all human beings deserve respect. A human is the only being capable of self-reflection and comprehension of the meaning of life.40

The principles of ontologically- based personalism in bioethics may be summed up as follows:31

* the defence, intangibility and sacred ness of human life;

* the therapeutic principle whereby

* any intervention on life is justified only if it has a therapeutic purpose;

* the freedom and responsibility principle, where freedom recognizes respect for life as its objective limitation;

* the sociality and subsidiarity principle, consisting of the achievement of common good through individual well-being.

Some consider the traditional value of the person as a cumbersome dimension. Hence some modern thinkers focus on the individual but not on the person. Post modern philosophers not only dissolve the concept of person but also that of subject.41 Excessive positions like these are also present in bioethics. Still bioethics, especially when applied to clinical and experimental issues, is generally attentive to the individual person. The problem arises in defining the person and the moment when he/she begins and ends, from the status of the human embryo to the dignity of the dying. Personalism strongly emphasizes the need to protect the weakest and the sickest persons in society. In a personalistic view, the being and dignity of the person are fundamental and inalienable values. Moral actions can thus be measured in respect of the person’s being and dignity.42 This can be stated through a formulation that is similar to the second Kantian imperative: the person “should never be treated as a simple means, as an instrument that can be used for the purpose of achieving any other end: on the contrary, the person should be treated as an end, or – more specifically – respecting, and in some cases promoting, its own ends”.43 In Kant’s philosophy, however, this imperative has a negative connotation.44 Personalism does not simply exclude negative behaviours but requires positive attitudes.

Personalism and its application to public health

When applied to public health, personalistic principles include a set of duties which derive from respect of the person. These include respect of the individual’s autonomy, the safeguard of confidentiality within a collective and potentially de-personifying framework, the effort to guarantee equity and equal opportunities for everyone in the allocation of health-care resources.45,46 Personalism is not opposed to other ethical theories as it can have both points in common and divergences with them. In a personalist view, for example, the consequentialist-utilitarian approach can certainly be part of a public-health policy as long as the lives and well-being of individuals are preserved.47

Respect for individual rights and freedom is also an essential requisite of human coexistence if it comes with regard to the “correct exercising” of freedom that is bonded to respect for life. In public health there might be cases where freedom must be sacrificed to the advantage of the common good. A minimum limit however should never be exceeded and decisions should never heavily penalize a person’s living conditions. If the wellbeing of the community is at stake, personalism does not exclude “moderate patronizing.” Gerald Dworkin defines patronizing as “the interference with a person’s freedom of action for reasons which exclusively refer to the wellbeing, good, happiness, needs, interests or values of a person who is subjected to the coercion”.48 A moderate form of patronizing is justified both in serious or emergency circumstances (such as during epidemics where persons need to be isolated to prevent the spread of a disease), and in routine conditions where the subject may not be in full charge of the situation and hence it becomes necessary to force certain behaviours (such as the compulsory wearing of seatbelts).

Cautionary policies based on the precaution principle are also significant in terms of public-health ethics. When scientific data are contradictory or quantitatively scarce, it is possible to appeal the precautionary principle. This principle shows the need for making temporary decisions that may be modified on the basis of new facts that eventually become known.49

Some authors have singled out the precautionary principle as one fundamental value in public-health ethics, alongside justice, transparency and the choice of the least restrictive alternative for people’s autonomy.50 Special importance has been attached to the precautionary principle by European ethics.51 Its relevance is also underlined by the Italian Committee on Bioethics and the Pontifical Council for Justice and Peace, with reference to the ethics of social and collective problems and to environmental issues.52,53 Personalism strongly values principles of sociality and solidarity. However, the individual’s good is the basis for common good. The social dimension of personalism, which was highly emphasized at the beginning of the 1920s, contributed to the renewal of classical personalism and the foundation of the modern personalism of Emmanuel Mounier and Jacques Maritain.54,55

Conclusion

Personalism proposes firm points to be respected by health-care policies and positively proposes “principles” such as solidarity and subsidiarity to be valued in public-health ethics. Critics of this approach may consider personalism as a theoretical speculation with limited operational relevance. However, we agree with Taboada & Cuddeback that “answering philosophical questions?about the essence and the value of human health, is crucial for the solution of political problems such as how to legislate health care policy”.56 The founding basis of universalism, personalism and solidarity as an anthropological concept is shared, today, by representatives of different cultures.57 If we want to promote development from a health viewpoint, we must move from a solitary, individualistic approach to a personalist approach in an integral sense. Going forward, we must rethink the concept of coexistence in our world, starting from the assumption that we all belong to the human species, with consideration of our different identities and, therefore, shift from the “individual” to the “person.”

Competing interests: None declared.

Resume

Approche personnaliste de l’ethique en sante publique

Nous commencons par donner un apercu de l’evolution historique de la sante publique. Puis nous presentons certains codes deontologiques et principes ethiques de cette discipline. Nous mettons en lumiere les difficultes pour definir une ethique de la sante publique, en decrivant plus explicitement trois d’entre elles qui concernent : (i) les possibilites d’adaptation de la sante publique aux principes classiques de la bioethique, (ii) le devoir de respect et de sauvegarde de l’individu lorsqu’on agit dans l’interet de la collectivite, caracteristique de la sante publique ; (iii) la nature appliquee de cette discipline et le manque general d’interet pour les implications ethiques des interventions collectives (par comparaison avec la recherche).

Nous mentionnons ensuite certaines propositions elaborees a partir des “principes” bioethiques en vigueur en Amerique du Nord et de points de vue utilitaires, liberaux et collectifs. En s’appuyant sur d’autres approches, le personnalisme est presente comme une theorie offrant un jeu coherent de valeurs et de principes de substitution applicables a la sante publique.

Resumen

Enfoque personalista de la etica en salud publica

En primer lugar se ofrece aqui una panoramica del desarrollo historico de la salud publica, para presentar a continuacion algunos codigos deontologicos en materia de salud publica y determinados principios eticos. Destacamos las dificultades que entrana la definicion de una etica en salud publica, dedicando especial atencion a tres de ellas relacionadas con: (i) la adaptabilidad de los principios clasicos de bioetica a la salud publica; (ii) el deber de respetar y proteger a los individuos aunque se adopte la perspectiva comunitaria caracteristica de la salud publica; y (iii) el hecho de que la salud publica esta orientada a las aplicaciones y de que en general se presta poca atencion a las implicaciones eticas de las intervenciones colectivas (en comparacion con la investigacion).

Por ultimo, se mencionan algunas propuestas elaboradas a partir de “principios” de bioetica emanados de America del Norte y de nociones utilitaristas, liberales y comunitarias. Partiendo de otras perspectivas, el personalismo se perfila como una teoria que brinda un conjunto coherente de valores y principios alternativos pertinentes para la salud publica.

…

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Carlo Petrini(a) & Sabina Gainotti(b)

a Office of the President, National Institute of Health, Rome, Italy.

b National Centre of Epidemiology, Control and Health Promotion, National Institute of Health, Rome, Italy.

Correspondence to Carlo Petrini (e-mail: [email protected]).

doi:10.2471/BLT.08.051193

(Submitted: 11 January 2008 – Revised version received: 10 June 2008 – Accepted: 10 June 2008)

Copyright World Health Organization Aug 2008

(c) 2008 World Health Organization. Bulletin of the World Health Organization. Provided by ProQuest LLC. All rights Reserved.

By Tilburt, Jon C Kaptchuk, Ted J

Abstract Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk-benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk-benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By “cross-training” investigators, and investing in safety- monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health. Bulletin of the World Health Organization 2008;86:594-599.

(ProQuest: … denotes formula omitted.)

Introduction

Traditional herbal medicines are naturally occurring, plant- derived substances with minimal or no industrial processing that have been used to treat illness within local or regional healing practices. Traditional herbal medicines are getting significant attention in global health debates. In China, traditional herbal medicine played a prominent role in the strategy to contain and treat severe acute respiratory syndrome (SARS).1 Eighty per cent of African populations use some form of traditional herbal medicine,2,3 and the worldwide annual market for these products approaches US$ 60 billion.2 Many hope traditional herbal medicine research will play a critical role in global health. China, India, Nigeria, the United States of America (USA) and WHO have all made substantial research investments in traditional herbal medicines.2 Industry has also invested millions of US dollars looking for promising medicinal herbs and novel chemical compounds.4,5 This is still a relatively modest investment compared to the overall pharmaceutical industry; however, it raises interesting ethical questions, some of which are not faced in more conventional drug development.

As attention and public funding for international traditional herbal medicine research collaborations grows, more detailed analysis of ethical issues in this research is warranted. Scant literature has addressed selected issues such as informed consent and independent review related to traditional herbal medicine research.6,7 Here we apply a practical, comprehensive and widely accepted ethical framework to international traditional herbal medicine research.8 We examine in detail difficult questions related to social value, scientific validity and favourable risk-benefit ratio. We conclude with implications for future research in this area, focusing on the importance of collaborative partnership.

Case

A government agency from a developed country is conducting an HIV- treatment trial in Africa. A traditional herbal medicine, Africa Flower, has been used for decades to treat wasting symptoms associated with HIV. Local traditional medicine healers believe Africa Flower is an effective antiviral. It is already widely used for immune boosting in AIDS. In vitro pharmacokinetic studies suggest potential interference with vaccines, and animal models show liver toxicity at very high doses. There are no systemic side- effects reported for humans in the literature. A few case series have shown mixed results. Local leaders are requesting the government agency conduct a large, randomized controlled trial (RCT) of Africa Flower to test its efficacy as a novel adjunctive therapy to slow progression to AIDS.

Ethical framework

Cases like these present challenging questions related to the role of traditional herbal medicines in public health. In general, international research on traditional herbal medicines should be subject to the same ethical requirements as all research related to human subjects.9 An ethical framework previously outlined by Emanuel et al. and revised for international research8 offers a useful starting point for thinking about the ethics of international traditional herbal medicine research. This framework includes eight ethical requirements for clinical research (Table 1).8 These ethical requirements are universal and comprehensive but must be adapted to the particular social context in which the research is implemented.8 Of these, fair subject selection, independent review, informed consent, and respect for enrolled subjects have been discussed previously in the literature on the ethics of global health research and raise few issues unique to international traditional herbal medicine research.8 However, social value, scientific validity, and favourable risk-benefit ratio raise specific challenges in international herbal medicine research that have not been adequately discussed.

Social value

All research should hold the potential to achieve social value. Different entities may view the social value of traditional medicine research differently. Public-health officials are often eager to define the safety and effectiveness of herbal medicines for conditions such as malaria.3 Conversely, harm can arise with the unscrupulous use of herbs such as Africa potato (various Hypoxis species).7 While some claim that such medicines have “stood the test of time”, they nonetheless pose serious challenges to investigators and regulators from developed countries, in which standards of proof are closely linked to proven efficacy in RCTs. Accordingly, there has been a serious investment in herbal medicine research by public- health bodies in many countries. China recently launched a safety research programme focusing on herbal medicine injections from traditional Chinese medicine.10 South Africa recently included the need for investigating traditional medicines within its national drug policy.11

In the USA, the National Center for Complementary and Alternative Medicine at the National Institutes of Health spent approximately US$ 33 million on herbal medicines in fiscal year 2005; in 2004 the National Cancer Institute committed nearly US$ 89 million to studying a range of traditional therapies.12 While this scale of investment pales in comparison to the total research and development expenses of the pharmaceutical industry, it nevertheless reflects genuine public, industry and governmental interest in this area.

While public-health entities may be concerned with defining the risks and benefits of herbal medicines already in use, entrepreneurs and corporations hope herbal medicines may yield immediate returns from herbal medicine sales, or yield clues to promising chemical compounds for future pharmaceutical development. They test individual herbs, or their components, analysed in state-of-the-art high-throughput screening systems, hoping to isolate therapeutic phytochemicals or biologically active functional components. In 2006, Novartis reported that it would invest over US$ 100 million to investigate traditional medicine in Shanghai alone.4,5

Nongovernmental organizations may be primarily interested in preserving indigenous medical knowledge. One such organization, the Association for the Promotion of Traditional Medicine (PROMETRA), based in Dakar, Senegal, is “dedicated to preserving and restoring African traditional medicine and indigenous science”.13 Governments in developing countries may want to use traditional herbal medicine research to expand the influence of their culture’s indigenous herbal practices in the global health-care market. For instance, Nigeria’s president recently established a national committee on traditional medicine with the expressed desire to boost Nigeria’s market share of traditional medicine.14 In developed countries, the “need” for this research may be to protect the public.

The perceived need for the research may justifiably differ across countries, but without some basic agreement on the primary source of social value for the research it may be difficult to judge its ultimate impact. In the Africa Flower case above, before agreements to study a herbal medicine are decided, partners must fully discuss potential differences about the perceived “need” for the research through public forums or structured debates. Based on these frank discussions, partners can assess whether the social values of partner countries are sufficiently compatible to warrant a research partnership.

Scientific validity

Part of ensuring the social value of research includes devising and implementing sound science. Although international collaborative research on herbal medicine is no exception, discussing scientific validity as an ethical requirement raises some specific challenges, including the meaning of scientific validity, establishing inclusion and exclusion criteria, using appropriate outcome measures, and determining appropriate study designs.

Balancing internal and external validity

Building a valid basis for knowledge in herbal medicine will require balancing two aspects of scientific validity: internal and external validity.15 Internal validity means the research must reliably test hypothesized relationships between an intervention and an outcome under controlled conditions. Internally valid research will typically try to answer a focused research question that is salient within the vocabulary and methods of the scientific community at the time the research is conducted. External validity refers to the applicability of the research results to a target population outside the experimental conditions of the research study. External validity must always be weighed against the need for rigorous internally valid research. This tension between internal and external validity can be illustrated by a recent herbal medicine trial of Echinacea angustifolia extract for prevention of parainfluenza virus infection.16 The study was conducted under rigorous experimental conditions, but many herbalists pointed out that study conditions did not sufficiently reflect how these medicines are actually used. Null treatment trial results like these prompt questions about the external validity (i.e. value and meaning) of the research. Was the herbal medicine truly ineffective, or did the experiment not reflect the herb’s use in “real-world” practice? In herbal medicine there are often huge variations in the way in which the medicines are used in herbalist practice, including herb source, preparation, dose and indication. Because traditional herbal medicine practitioners may be unregulated and their products lacking in standardization, it may be difficult to generalize the results from a formal, structured and highly monitored trial to what will happen in the widespread dissemination of the herbal medicine. Nevertheless, herbal medicine research must endeavour to achieve a balance between internal and external validity.

Inclusion and exclusion criteria

To ensure that research results are externally valid, the inclusion and exclusion criteria for research participation should fit with existing diagnostic categories in the target population specified by the research question. However, conceptualizations of health and illness can vary across medical systems and populations, making agreement on valid inclusion and exclusion criteria for international herbal medicine research collaborations more difficult to achieve.

During the SARS epidemic, traditional Chinese medicine (TCM) practitioners involved in the care of SARS patients characterized patients based on nosological categories derived from TCM including “deficiency of chi and yin” as well as “stagnation of pathogenic phlegm”.17 Designing clinical trials using these kinds of TCM categories as inclusion criteria would require significant additional effort and biomedical flexibility to implement. If one wanted to test whether TCM works for populations in south-east Asia affected by a SARS-like illness, adapting the science to include traditional diagnostic categories may be critical for its ultimate external validity.

If American researchers want to test a herb’s effects on heart failure, they might use the New York Heart Association classification as part of the inclusion/exclusion criteria. However, this classification makes little sense from a TCM perspective, in which heart failure may be viewed primarily as either a heart yang chi deficiency or a kidney yang deficiency.18 TCM practitioners may prefer to categorize patients based on pulses, tongue examination, and other elements of traditional diagnosis. Investigators have simultaneously used both biomedical entry criteria and stratified for TCM diagnosis.19 Such an approach is scientifically ideal because of its ability to maximize the external validity of results.

Valid outcome measures

International herbal medicine research must use outcome measures that accurately capture the effects conferred by herbal medicines. However, constructs such as “physical functioning” or “psychological well-being” measured by the SF-36 quality of life instrument make little sense within the terminology and ideas of TCM.20 Therefore to accurately measure a TCM herb’s effects on quality of life, some investigators have constructed and validated analoguous measures that more faithfully detect the effects of TCM interventions that make sense within that healing tradition.20,21 Ideally, when new measures are introduced, they should overlap with existing outcome measures, so that the research can adequately contribute to the existing body of knowledge.

Determining research design

While it is generally agreed that all human subjects research must maintain valid study designs, questions arise about the characteristics of a valid research design. Two extreme positions are often defended. At one extreme, some researchers trained in biomedical methods of clinical investigation argue that the only valid source of knowledge regarding clinical efficacy must come from one type of research design, the randomized double blind, placebo- controlled trial. They argue that any deviations from this gold standard of scientific validity amount to worthless science.

At the other extreme, critics of biomedical research conducted on traditional medicines charge that attempts to evaluate traditional therapies with biomedical methodologies may fail to generate true knowledge, since that knowledge itself depends on a scientific vocabulary that only makes sense from within the concepts of biomedicine.22-24 They worry that “standard notions of … experimental design criteria represent an imperialistic ‘western’ mode of thinking”.22,24

Research on herbal medicines should typically employ experimental research designs such as the RCT. Even if research tools (including the RCT) are imperfect,25 they are thus far the best methods we have for furthering our knowledge.9,15 Consider how RCT designs could be implemented in TCM, in which treatments are individualized to patients, often incorporating several, or even dozens, of herbs in a customized preparation. Despite these complexities, investigators have successfully adapted double-blind RCT designs to complex individually tailored Chinese herbs. Bensoussan et al. conducted a three-arm trial in which they tested the comparative clinical efficacy of standard complex herbal medicines, customized therapy and placebo.26 Standard and customized therapy were comparably beneficial as compared to placebo. In other instances, cluster RCTs can allow for practitioner variability, while still rigorously testing the efficacy of a therapeutic approach. In cross-cultural settings, researchers cannot merely adopt alternative designs in an ad hoc manner, but must reflect on and refine their research question, and find a design that best answers the research question within the given cultural context.

In recent years, growing attention has been paid to a group of additional important ethical issues surrounding publication bias, financial conflicts of interest, and clinical trial registries. In the arena of traditional herbal medicine, these same issues apply, and when cross-cultural differences exist in the definitions of valid science, as is the case in traditional herbal medicine research, these questions compound. For instance, until recently, there was a tendency to see only positive studies published in China. It is, therefore, critically important to the long-term scientific credibility of international traditional herbal medicine research that, at the outset, partners agree about the standards of scientific conduct, the disclosure of financial relationships, registration of clinical trials, and adequate reporting of trial results.

Favourable risk-benefit ratio

In international herbal medicine research, several practical challenges arise in making accurate risk-benefit determinations. Typically, in American pharmaceutical development, a step-wise process of drug testing occurs – a compound is isolated, tested in tissue cultures and animals, and then investigated in phase 1, 2 and 3 clinical trials. However, herbal medicines are already in widespread use, are often used in combination, and are drawn from plant sources with their own variability in species, growing conditions and biologically active constituents. They often come into use by a process of trial and error, or over centuries. Accordingly, in clinical herbal medicine research there is rarely a strong preclinical basis for dosing, and there are significant looming questions about product purity, quality, chemical stability and active constituents at the time herbal medicine trials are proposed.27,28

Initiating large-scale research trials in such circumstances raises questions about whether the risks and benefits of research participation can be accurately ascertained. Those reviewing protocols should factor in the uncertainty associated with product variability in determining whether a herbal medicine trial has a favourable risk-benefit ratio. However, protocol reviewers (i.e. institutional review boards) should not presume that because they are personally unfamiliar with a herbal preparation that there is no credible or valuable background evidence regarding safety and potential efficacy. While researchers should provide such information in protocol materials, reviewers must remain aware of the role their own lack of familiarity may play in their ultimate judgements of risks and benefits of the research.

Researchers increasingly agree that it is important to establish a rational basis for dosing and standardization of biologically active compounds before conducting large-scale treatment trials. 29,30 These efforts can improve investigators’ ability to assess the risks and benefits of participation in large-scale herbal medicine trials. Likewise, more rigorous monitoring of adverse events and standardized reporting of research results for both safety and efficacy data will improve long-term efforts to enhance risk- benefit ratio determination for trial participation.31 Cultural factors also may influence judgements of the risks and benefits in herbal medicine research. For instance, a cultural familiarity with many traditional Chinese herbal medicines in China may promote a familiarity bias, accepting a widespread cultural assumption of safety, based on the historical use of herbal medicines.32 There may also be a cultural difference in emphasis placed on standardized adverse events reporting in China.33 These cultural differences make achieving agreed-upon standards of favourable risk-benefit ratio more difficult. In order for international collaborative herbal medicine research to achieve its objectives, it will be important to establish standards of evidence for demonstration of safety before conducting large-scale clinical trials evaluating the efficacy of herbal medicines.

Improving science through collaborative partnership

How can international collaborative herbal medicine trials achieve the ethical requirements outlined above? Collaborative partnership, the first requirement for international research ethics, provides both the rationale and the context for achieving appropriate application of the other ethical requirements. Partners in these collaborations must share vocabulary for all the requirements, especially for social value, scientific validity, and favourable risk-benefit ratio. How can agreed-upon language be achieved? As illustrated here, these challenges are significant. In the case presented earlier, investigators should have reservations about implementing a large-scale clinical trial for Africa Flower. Nevertheless, the local interest in this substance may be valid and deserve some additional preliminary investigation. Collaborative partnership displays a commitment by all parties in international research agreements to work together for common language and goals.

To achieve collaborative partnership, parties can engage in structured methods of democratic deliberation to devise shared language and concepts for research. These methods have been used to bring different parties together in a safe and collegial process of decision-making.34 Over time, collaborations could “cross-train” basic and clinical investigators to more fully appreciate the concepts and practices of the traditional herbal medicine traditions, and developing host countries would need to develop the basic literacy, knowledge and skills among traditional medicine practitioners so that they see the value of rigorous clinical research.2 With a sustained investment like this, it will become increasingly possible to conduct sound international scientific investigation on traditional herbal medicine. Furthermore, sustainable collaborative research partnerships would benefit from robust and independent adverse-event reporting systems for herbal medicines so that the risk-benefit ratio for herbal medicine research can be more clearly defined.

Ethical challenges in international traditional herbal medicine call for a comprehensive framework. Addressing these challenges requires collaborative partnership that implements sound research designs. So envisioned, international herbal medicine research can contribute to global health.

Acknowledgements

Franklin G Miller and Jack Killen generously read and offered helpful suggestions on earlier versions of this paper.

Funding: TJK is a consultant for Kan Herbal Company, Scotts Valley, CA, USA. Partial funding for TJK was provided by the National Center for Complementary and Alternative Medicine at the National Institutes of Health, Bethesda, MD, USA.

Competing interests: None declared.

Resume

Recherche en phytotherapie et sante dans le monde : analyse ethique

Les gouvernements, les agences internationales et les entreprises investissent de plus en plus dans la recherche en phytotherapie traditionnelle. Cependant, les difficultes ethiques de cette recherche sont peu abordees dans la litterature. Dans cet article, nous appliquons les concepts d’un cadre ethique complet a la recherche clinique en phytotherapie traditionnelle internationale. Nous examinons en detail trois dimensions sous-estimees et essentielles du cadre ethique, dans lesquelles se posent des problemes particulierement difficiles pour la recherche internationale en phytotherapie : la valeur sociale, la validite scientifique et le ratio risque/benefice favorable. La definition de concepts partages pour la valeur sociale, la validite scientifique et le rapport risque/benefice favorable applicables a l’ensemble de la recherche en collaboration internationale se heurte a des difficultes majeures. Nous affirmons neanmoins que le partenariat collaboratif, et notamment la deliberation democratique, offre le contexte et le processus pouvant et devant permettre de resoudre beaucoup des problemes ethiques rencontres dans la recherche internationale en phytotherapie. Moyennant une > des chercheurs et des investissements en infrastructures de surveillance de l’innocuite, l’identification des problemes par ce cadre complet favorisera une recherche en phytotherapie internationale valable sur le plan ethique et contribuera a la sante dans le monde.

Resumen

Investigacion fitoterapeutica y salud mundial: analisis etico

Gobiernos, organismos internacionales y empresas estan invirtiendo cada vez mas en la investigacion de medicamentos herbarios tradicionales. Sin embargo, son escasas las publicaciones que abordan los problemas eticos asociados a esas investigaciones. En este articulo aplicamos los conceptos manejados en un marco etico amplio de regulacion de las investigaciones clinicas a las actividades internacionales de investigacion de medicamentos herbarios tradicionales. Examinamos en detalle tres dimensiones clave pero subestimadas del marco etico en las que se plantean cuestiones particularmente dificiles para la investigacion internacional de esos medicamentos: valor social, validez cientifica y relacion riesgo-beneficio. El proceso de consenso en torno a lo que deba entenderse por valor social, validez cientifica y relacion riesgo-beneficio favorable en las investigaciones internacionales en colaboracion entrana retos importantes. Sin embargo, sostenemos que hay formulas de colaboracion, en particular la deliberacion democratica, que brindan un contexto y unos procedimientos mediante los que se pueden, y se deben, resolver muchos de los dilemas eticos asociados a las investigaciones internacionales en materia de medicina herbaria. Formando de manera interdisciplinaria a los investigadores e invirtiendo en infraestructuras de vigilancia de la seguridad, las cuestiones identificadas mediante este marco integral pueden fomentar la realizacion de investigaciones internacionales de medicamentos herbarios eticamente validas que contribuyan a la salud mundial.

…

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10. Chong W. China launches traditional medicine safety research. Science and Development Network; 2006. Available from: http:// www.scidev.net/en/news/china-launches-traditional-medicine-safety- researc.html [accessed on 1 November 2006].

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14. Adelaja A. Nigeria boosts research into traditional medicine. Science and Development Network; 2006. Available from: http:// www.scidev.net/en/news/nigeria-boosts-research-into-traditional- medicine.html [accessed on 15 February 2007].

15. Linde K, Jonas WB. Evaluating complementary and alternative medicine: the balance of rigor and relevance. In: Jonas WB, Levin JS, eds. Essentials of complementary and alternative medicine. Baltimore: Lippincott Williams & Wilkins; 1999 pp. 57-71.

16. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005;353:341-8. PMID:16049208 doi:10.1056/ NEJMoa044441 17. Boli Z, Shuren L, Junping Z, Hongwu W. Manifestation of symptoms in patients with SARS and analysis of the curative effect of treatment with integrated Traditional Chinese Medicine and Western medicine. In: SARS: clinical trials on treatment using a combination of Traditional Chinese Medicine and Western medicine. Geneva: WHO; 2003. pp. 53-61.

18. Kaptchuk TJ. The web that has no weaver: understanding Chinese medicine. New York: Contemporary Books; 2000.

19. Macklin EA, Wayne PM, Kalish LA, Valaskatgis P, Thompson J, Pian-Smith MC, et al. Stop hypertension with the acupuncture research program (SHARP): results of a randomized, controlled clinical trial. Hypertension 2006; 48:838-45. PMID:17015784 doi:10.1161/01.HYP.0000241090.28070.4c

20. Zhao L, Chan K. Building a bridge for integrating Chinese medicine into conventional healthcare: observations drawn from the development of the Chinese Quality of Life Instrument. Am J Chin Med 2005;33:897-902. PMID:16355446 doi:10.1142/S0192415X05003533

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28. Ernst E. Heavy metals in traditional Chinese medicines: a systematic review. Clin Pharmacol Ther 2001;70:497-504. PMID:11753265

29. Guidance on designing clinical trials of CAM therapies: determining dose ranges. National Center for Complementary and Alternative Medicine; 2003. Available from: www.nccam.nih.gov/ research/policies/guideonct.htm [accessed on 1 November 2006].

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31. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier for the CONSORT Group. Reporting randomized controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med 2006; 144:364-7. PMID:16520478

32. Lam TP. Strengths and weaknesses of traditional Chinese medicine and Western medicine in the eyes of some Hong Kong Chinese. J Epidemiol Community Health 2001;55:762-5. PMID:11553662 doi:10.1136/jech.55.10.762

33. Leung AY. Traditional toxicity documentation of Chinese materia medica – an overview. Toxicol Pathol 2006;34:319-26. PMID:16787890 doi:10.1080/01926230600773958

34. Gastil J, Levine P, eds. The deliberative democracy handbook: strategies for effective civic engagement in the 21st century. San Francisco, CA: Wiley; 2005.

Jon C Tilburt(a) & Ted J Kaptchuk(b)

a Department of Clinical Bioethics, National Institutes of Health, Bethesda, MD, United States of America.

b Osher Institute, Harvard Medical School, Boston, MA, USA.

Correspondence to Jon C Tilburt (e-mail: [email protected]).

doi:10.2471/BLT.07.042820

(Submitted: 2 April 2007 – Revised version received: 2 October 2007-Accepted: 25 October 2007)

Copyright World Health Organization Aug 2008

(c) 2008 World Health Organization. Bulletin of the World Health Organization. Provided by ProQuest LLC. All rights Reserved.

By Chew, H H Abuzeid, A; Singh, D; Tai, C C

ABSTRACT We report an unusual case of cutaneous mucormycosis in a 17-year-old man who had no risk factors for fungal infection. The aggressive nature of cutaneous mucormycosis is illustrated. A high index of suspicion is crucial for identifying and preventing progression of this disease, which can lead to limb amputation, even death. Extra vigilance should be given to those who are immunocompromised, including those receiving short courses of steroids. Early recognition, prompt surgical intervention and initiation of an appropriate antifungal treatment are crucial in the management of this rare but potentially limb- and life-threatening infection.

Key words: amputation; fungi; mucormycosis; surgical wound infection

INTRODUCTION

Mucormycosis is usually an opportunistic infection in patients with chronic debilitating diseases, particularly uncontrolled diabetes, or those receiving immunosuppressive agents. It is caused by fungi of the class Zygomycetes, order Mucorales. Mucorales are the third commonest cause of invasive fungal infections in humans and cause the highest mortality.1 Once established, mucormycosis spreads rapidly with widespread vascular invasion and can result in death. Cutaneous infection can occur in patients with traumatic injuries to the skin and soft tissues,2,3 but has not been reported in an immunocompetent patient in a sterile environment. We present an unusual case of cutaneous mucormycosis that eventually led to amputation of the hand.

CASE REPORT

In 2003, a 17-year-old man presented to our hospital with a closed Smith’s fracture of his right hand following a traffic accident. He underwent open reduction and internal fixation under general anaesthesia within 6 hours of injury. A 3-cm incision was made on the volar radial aspect of his wrist, and the fracture was reduced and fixed with a buttress plate. The wound was closed with subcuticular sutures and dressed in sterile Mepore (Molnlycke, Sweden) and cotton wool. A below-elbow plaster of Paris cast was applied.

At extubation, the patient developed acute laryngospasm and was admitted to the intensive care unit for ventilation. He subsequently developed adult respiratory distress syndrome and was treated with hydrocortisone (100 mg twice a day) for 2 weeks and intravenous cefuroxime (750 mg 3 times a day) for 10 days. On day 9, the surgical wound was inspected and noted to be clean, dry, and healed. The wound was redressed with sterile Mepore and cotton wool, and a Futura splint was applied.

On day 12, a blister was noted at the distal site of the incision. The blister burst on day 16 and left an erythematous area that subsequently became necrotic with an overlying dark eschar that bled spontaneously. On day 17, his white blood cell count rose to 12×109 cells/l. No neutrophil function tests for neutrophil phagocytosis, chemotaxis, and intracellular killing were performed. Microscopy and cultures of wound swabs revealed a mixed growth of Enterococcus faecalis and methicillin-resistant Staphylococcus aureus. Intravenous teicoplanin (400 mg once daily) was commenced but the infection progressed rapidly. Surgical debridement was performed at day 20. An extensive area of tissue necrosis with invasion of the underlying vascular structures was noted. Microscopy of the excised tissue revealed non-septate hyphae and vascular invasion consistent with mucormycosis (Fig.). The patient was immediately started on a course of intravenous amphotericin B (0.5 mg/kg/ day) and the hydrocortisone was stopped, but the vascular invasion had led to thrombosis of the right ulnar and radial arteries. A right forearm amputation was performed on day 24. The patient made an uneventful recovery and was discharged on day 37.

DISCUSSION

Fungi belonging to the order Mucorales are ubiquitous in the environment and have been isolated in up to 22% of hospital air samples.1 Despite this continual exposure, they are not common infectious agents, which is evidence of their avirulence. Healthy individuals have strong natural immunity to the Mucorales; mucormycosis usually only occurs in immunocompromised patients with any of the predisposing factors (Table 1). Depending upon the primary site of involvement, mucormycosis can be classified as rhinocerebral, pulmonary, gastrointestinal, disseminated, miscellaneous or cutaneous.4 Cutaneous mucormycosis, as seen in our patient, constitutes about 10% of all cases.1

Mucorales are incapable of penetrating intact skin, and infection requires direct inoculation through a compromised cutaneous barrier. Patients who are at risk usually have multiple injuries or burns associated with extensive tissue damage or soil contamination.2,4 Infection of a clean surgical wound is extremely rare. Three cases of postoperative mucormycosis in non-trauma patients following exposure to contaminated surgical adhesive (Elastoplast) have been reported.5 Mucoraceae spores have been subsequently demonstrated in non-sterile adhesive dressings (Elastoplast), cloth tape, and even tongue depressors.6 We do not know whether the sterile dressing used on our patient was contaminated as the dressings were discarded before the diagnosis of mucormycosis was made. Tests performed on the same batch of sterile dressings did not reveal any evidence of contamination with mucoracae spores. Investigations of the ventilator, endotracheal tube, intravenous/central venous lines, and air sampling of the intensive care unit also failed to detect any mucoracae spores. Neutrophil function tests should have been conducted to screen for a heterozygous chronic granulomatous disease of childhood that can present much later, particularly when the affected person is taking mild immunosuppressants. Even severe glucose 6 phosphate dehydrogenase deficiency can affect neutrophil and monocyte function.

One possibility is that the spores were on the skin of the patient, as part of the skin flora, or introduced at the time of accident. It is known that solutions such as providone iodine used to prepare skin preoperatively are unable to eradicate inert spores from a patient, and this may be the source of the initial inoculum. Our patient had no risk factors for the development of mucormycosis. Short courses of steroids, as given to our patient, have not been known to predispose patients to mucormycosis but it is possible that the 2-week course of hydrocortisone compromised his immune system sufficiently to make him vulnerable to fungal infection.

The most characteristic feature of mucormycosis is hyphal invasion of blood vessels. There are 3 clinical stages of cutaneous mucormycosis, based on the degree of vascular invasion achieved by the fungus (Table 2). Early tissue biopsy is the gold standard for diagnosis, but a frozen section may be performed if a rapid diagnosis is required. Cultures of the wound discharge and exudates can be unreliable as results are positive in only 30% of cases with histology-proven mucormycosis.6 Treatment of virulent cutaneous mucormycosis involves discontinuing all immunosuppressive drugs and commencing parenteral antifungal therapy. The mainstay of treatment, however, is early and aggressive surgical debridement. This approach has been reported to reduce overall mortality from 60% to 11%.7 Mortality from cutaneous mucormycosis usually results from spread of the fungus to vital organs not amenable to surgical excision, and is directly dependent upon the speed of diagnosis and institution of treatment. A high index of suspicion is crucial for identifying and preventing progression of the disease and mucormycosis must always be considered as a differential diagnosis, particularly when wound infections respond poorly to antibiotic therapy and display features of mucor infection. Extra vigilance should be given to those who are immunocompromised, even those who are only receiving short courses of steroids. Early recognition, prompt surgical intervention and initiation of an appropriate antifungal treatment are crucial in the management of this rare but potentially limb- and life-threatening infection.

Table 1

Risk factors for mucormycosis

Risk factors for mucormycosis

Diabetes mellitus

Myeloproliferative disorders

Acquired immunodeficiency syndrome

Organ transplantation

Renal failure

Polytrauma

Burns

Intravenous drug abuse

Long-term corticosteroid therapy

Cytotoxic chemotherapy

Broad-spectrum antibiotic therapy

Deferrioxamine therapy

REFERENCES

1. Losee JE, Selber J, Vega S, Hall C, Scott G, Serletti JM. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 2002;49:385-90.

2. Hay RJ. Mucormycosis: an infectious complication of traumatic injury. Lancet 2005;365:830-1.

3. Andresen D, Donaldson A, Choo L, Knox A, Klaassen M, Ursic C, et al. Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. Lancet 2005;365:876-8.

4. Hammond DE, Winkelmann RK. Cutaneous phycomycosis. Report of three cases with identification of Rhizopus. Arch Dermatol 1979;115:990-2.

5. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.

6. Greenberg RN, Scott LJ, Vaughn HH, Ribes JA. Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis 2004;17:517-25. 7. Eucker J, Sezer O, Graf B, Possinger K. Mucormycoses. Mycoses 2001;44:253-60.

HH Chew, A Abuzeid, D Singh, CC Tai

Department of Orthopaedic Surgery, Barnet General Hospital, London, United Kingdom

Address correspondence and reprint requests to: Dr Cheh-chin Tai, Department of Orthopaedic Surgery, University of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: [email protected].

Copyright Western Pacific Orthopaedic Association Aug 2008

(c) 2008 Journal of Orthopaedic Surgery. Provided by ProQuest LLC. All rights Reserved.

Alpha Innotech Corp. (OTCBB:APNO) today announced that it has entered into a five year Strategic Supplier Alliance Agreement with GE Healthcare (NYSE:GE). This agreement is a continuation and expansion of the previous OEM Agreement signed between the two companies in April of 2005.

Under the terms of the agreement, Alpha Innotech will continue to develop, manufacture and supply a full line of proprietary imaging systems to GE Healthcare. The products will be sold exclusively worldwide under the GE brand in the life science research and drug discovery markets.

“Over the past three years we have built a very strong relationship with GE Healthcare and are pleased to extend our partnership in commercializing life sciences imaging systems,” stated Sia Ghazvini, Vice President for Marketing and Business Development at Alpha Innotech. “Combining GE Healthcare’s worldwide reach and expertise in biological applications with Alpha Innotech’s expertise in imaging technologies will provide researchers with completely integrated products for their research.”

“We are happy to extend our partnership with Alpha Innotech and to work closely with them providing leading edge scientific imaging systems and developing next generation products. Our partnership with Alpha Innotech expands our imaging portfolio and provides researchers with a broad choice of imaging modalities,” said Ron Alves, Purchase Family Leader, GE Healthcare. “Alpha Innotech continues to be our partner because their commitment to company values and product performance complements our own.”

About Alpha Innotech Corp.

Founded in 1992 and with over 10,000 systems sold worldwide, Alpha Innotech is a leading developer, manufacturer and marketer of digital imaging and analysis systems for the life science research and drug discovery markets. Our goal is to combine instruments, reagents and bioinformatics software to offer integrated modular technology platforms for functional genomics, proteomics and cell analysis markets. Our customers include pharmaceutical and biotechnology companies as well as universities, medical centers, government research institutes and agencies worldwide. More information on Alpha Innotech can be found at the Company’s website www.alphainnotech.com.

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Its expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, performance improvement, drug discovery, and biopharmaceutical manufacturing technologies is helping clinicians around the world re-imagine new ways to predict, diagnose, inform, treat and monitor disease, so patients can live their lives to the fullest.

GE Healthcare’s broad range of products and services enable healthcare providers to better diagnose and treat cancer, heart disease, neurological diseases and other conditions earlier. Its vision for the future is to enable a new “early health” model of care focused on earlier diagnosis, pre-symptomatic disease detection and disease prevention. Headquartered in the United Kingdom, GE Healthcare is a $17 billion unit of General Electric Company (NYSE:GE). Worldwide, GE Healthcare employs more than 46,000 people committed to serving healthcare professionals and their patients in more than 100 countries. For more information about GE Healthcare, visit its website at www.gehealthcare.com.

Cautionary Note Regarding Forward-Looking Statements

This news release contains forward-looking information within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and is subject to the safe harbor created by those sections. These forward-looking statements involve a number of risks and uncertainties that include, but are not limited to, the Company’s ability to obtain additional financing if needed, the timing of the introduction and success of new products, and the Company’s growth prospects, that could cause actual results to differ materially from those anticipated or planned by these forward-looking statements. Please also refer to the risk factors described in our filings with the Securities and Exchange Commission, including our recent Form 10-KSB and Form 10-Q filed with the Securities and Exchange Commission. We do not intend to update the forward-looking information contained in this news release except as required by law.

By Barbara Holden

A high infant mortality rate haunts Shelby County. In this community it has become all too common for a baby to die in the first year of life.

In the past, it has been the heartbreak of families, with only a few others understanding the magnitude of their loss.

The issue was catapulted to the general community’s attention in 2005 by The Commercial Appeal’s award-winning series on infant mortality.

The Aug. 22 broadcast of the documentary “Babyland” on ABC’s “20/ 20” has further highlighted Shelby County’s struggle, leading more of us to understand.

“As painful as the story was to watch on television, it is exponentially more heartbreaking to see and hear the personal stories of our citizens who have lost children before they’ve even had a chance to live,” said Shelby County Mayor A C Wharton.

In 2006, Gov. Phil Bredesen and Wharton convened an infant mortality summit. Out of this came efforts like Shelby County’s Infant Mortality Reduction Initiative, Community Voice and Centering Pregnancy. These programs focus on reducing infant mortality rates in Shelby County. The recent national spotlight supports our need to continue this focus.

Now that more of us understand the problem, it is our collective responsibility to ensure that acceptance of premature births and infant deaths does not become a social norm in Shelby County. Although solving the systemic problems associated with these issues can seem almost paralyzing, our community does not have the luxury of hand-wringing when it comes to such critical issues.

Our challenge is not an easy one. There are no simple solutions. The systemic conditions that contribute to prematurity and infant death include poverty, community education, understanding the importance of prenatal care and a multitude of other factors.

These can be addressed only through long-term, intense and concentrated approaches.

We know there is a domino effect. We hope that comprehensive early childhood studies, such as the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) study coordinated by the Department of Preventive Medicine at the University of Tennessee Health Science Center, as well as other focused interventions by the Health Department, many local community organizations and the county mayor’s office, will help us understand how to keep that first domino from falling.

The drive to change this trend must radiate from the core of our community value system. We can be sure that it’s going to take our entire community to change it.

Like most public health issues, this one boils down to public will, resources and support.

It is essential that we continue this dialogue and continue to learn all we can about the causes of prematurity and infant death. This must include not only the medical but the social conditions associated with these issues.

Wharton recently summarized it well when he said, “While we have made significant local advances in educating the public and mentoring at-risk pregnant mothers through efforts such as Centering Pregnancy and Community Voice, our achievements will never be enough as long as one baby is lost before his or her first birthday to truly avoidable and preventable circumstances.”

The words “truly avoidable and preventable circumstances” are the key to our success. Can we prevent all infant deaths? No. Can we prevent all those that are “truly avoidable and preventable”? Absolutely.

Shelby County Mayor’s Office on Early Childhood and Youth infant mortality coordinator Antoinette Holman has received an influx of calls from people asking how they can help.

I hope you’ll do the same and give your time and talents to help.

To find out how you can participate in this important initiative, call the Mayor’s Office on Early Childhood and Youth at 526-1822.

For more information, visit at theurbanchildinstitute.org or dial 211 for the Public Library and Information Center.

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It is our responsibility to ensure that acceptance of premature births and infant deaths does not become a social norm in Shelby County, urges Barbara Holden .

Barbara Holden is a director at The Urban Child Institute.

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Originally published by Barbara Holden .

(c) 2008 Commercial Appeal, The. Provided by ProQuest LLC. All rights Reserved.

By Chris Arpe Gang

Memphians have often made the 30-mile trip to Holly Springs, Miss., to wander through the historic homes and churches that have been so carefully preserved in the charming city of about 8,000 residents.

Since 1998, visitors have been able to combine encounters with nature and antebellum architecture at Strawberry Plains Audubon Center a few miles north of the town square.

Sisters Margaret Finley Shackelford and Ruth Finley bequeathed their 2,500-acre farm and 1850s home to the Audubon Society to create a wildlife sanctuary with 200 species of birds, gardens filled with native plants, walking trails, forests and wetlands.

The center’s biggest event, the Hummingbird Migration Celebration, takes place Friday-Sunday. It typically draws about 7,000 people eager for a close encounter with the tiny birds that hover in the colorful flowers and syrup-filled feeders in the gardens at the center.

Hours are 9 a.m.-5 p.m. each day. Admission is $10 for adults; $7 for seniors; $5 for children under 5 and $3 for children under 3. Parking is free.

Hummingbird experts Bob and Martha Sargent will return to capture migrating birds so they can place featherweight aluminum bands on their tiny legs for research purposes.

A few lucky lookers will get to hold the ruby-throated hummingbirds in the palms of their hands before releasing them so they can continue their long journey to their winter nests in southern Mexico.

Young and not-so-young visitors will also be delighted with programs and exhibits on bats, Mississippi snakes, owls, frogs, woodpeckers, native plants, fish, salamanders, spiders and more. Nature walks led by naturalists are also available all three days. Guided wagon rides will operate on the hour from 11 a.m. to 4 p.m. Friday, Saturday and Sunday. Guided nature walks are scheduled all three days as well.

Kristin Lamberson, “weed woman” and horticulturist at the center, will give programs on the benefits of gardening with native plants along with Jesse Grantham, coordinator of the California condor recovery program for U.S. Fish and Wildlife Agency. Grantham was formerly director of the Mississippi Audubon office.

More information about the hummingbird celebration, including a detailed schedule of events, is available at msaudubon.org.

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While in Holly Springs

The Walter Place Estate Cottages and Garden is open for touring 2 p.m. daily. Admission is $20 for the complete package of tours that includes the historic home (circa 1858), cottages and gardens. Tickets for touring the gardens or cottages only are $7; $10 for house only. (888) 687-4765

Graceland Too , 200 East Gholson, is a one-of-kind shrine to Elvis. It’s open 24 hours a day, seven days a week. Admission: $5 (888) 687-4765

Where to Eat

Phillips Grocery , 541 East Van Dorn, (662) 252-4671. USA Today proclaimed their hamburgers “one of the world’s greatest.” Don’t miss fried green tomatoes and fried pies. Open Monday-Thursday 10 a.m.-4 p.m. Monday through Thursday; 10 a.m.-5 p.m. Friday; 10 a.m.- 6 p.m. Saturday.

Crossroads Fish Shack , 4078 Miss. 178 in Red Banks, is open from 4:30 to 9 p.m. Friday and Saturday and from noon to 8 p.m. Sunday. Catfish and hushpuppies are specialties. Red Banks is on old U.S. 78 just north of Holly Springs.

Accommodations

Court Square Inn Bed & Breakfast , 132 East College. (800) 926- 3686 Room Rates: $99-$145 HollySpringsInn.com

Le’Brooks Inn , 100 Brooks Road, (662) 252-5444. Rooms from $79 to $99 per night.

Sporting opportunities

Kirkwood National Golf Club & Cottages , 277 Palmer Lane, Miss. 4 W. (800) 461-4653, offers lodging packages for golfers or for those just wanting a quiet getaway in modern cabins. Room rates: $72- $112. kirkwoodgolf.com

Fitch Farms Galena Plantation Cabins , 955 Thomas Road, Waterford, about 10 miles from Holly Springs, (662) 252-8855, offers quail, deer and wild turkey hunting packages, with or without lodging and meals. Call for rates. fitchfarms.com

For information about things to do in Holly Springs go to visithollysprings.org or call (888) 687-4765

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Originally published by Chris Arpe Gang Special to The Commercial Appeal .

(c) 2008 Commercial Appeal, The. Provided by ProQuest LLC. All rights Reserved.

By Amy Moellering

AT AGE 6, Brielle Book is no stranger to Epi-Pens or ambulances or life-threatening situations.

She has severe food allergies and, as a first-grader at Bollinger Canyon Elementary School in San Ramon, the chances that she will accidentally come into contact with nuts or dairy products are very high.

Such contact can trigger anaphylaxis, a severe allergic reaction that can shut down her breathing passages. If not treated immediately, the condition can be fatal.

According to the Food Allergy and Anaphylaxis Network, or FAAN, more than 3.1 million children in the United States have food allergies, a number that has doubled in the last 10 years.

Brielle’s mom, Connie Book, says she feels she is always “on.” She can’t let her guard down for one moment.

“One thing I have learned just by being a parent is you have to be your child’s advocate and that it’s better to educate than dictate,” she said.

Many people don’t understand how lethal some foods can be to children with severe allergies. One person’s innocuous peanut butter sandwich could be fatal for another. Although it’s unrealistic to forbid schools from allowing certain foods, it is realistic to formulate procedures that will ensure the safety of children with severe allergies.

With this in mind, Book and fellow parents Stephanie Whiteman and Susan Ryu teamed up with Bollinger Canyon Principal Shawn Wells to develop a Food Allergy Protocol Plan that they are implementing this year. In addition, the committee is educating the community by sending home informative letters, showing a video about food allergies at Back to School Night, and preparing a skit that Girl Scouts will perform at a school assembly.

“We want to provide a safe and secure environment for every child while respecting the rights of others,” Wells said. “Through educating the community, we can all be friends in protecting these children.”

The Food Allergy Protocol Plan trains staff members and teachers in emergency procedures, including the administering of epinephrine. Children with severe food allergies have their photos available so staff and noontime supervisors can recognize them.

At lunch, a table is provided for kids with food allergies to sit together. Other children can sit there, too, but their food must be examined by a trained staff member or parent volunteer who understands the emergency plan of each child. That person will also wipe off the table before lunch.

If parents wish to bring a treat for the class, they agree to bring something without nuts or dairy products, or they inform the teacher who will notify the parent so she can prepare a safe alternative treat. Teachers also notify parents when food substances are used in projects, such as science.

How is the plan working? Since there are only five first-graders with severe allergies, some parents were concerned that the separate table would make them feel ostracized. That hasn’t happened.

“The table is actually full — with friends who want to sit there with the kids who have allergies,” Book said.

As for Brielle, she will be an ambassador at the FAAN walk on Sept. 20 in San Francisco’s Golden Gate Park. FAAN is a non-profit organization dedicated to educating the public about food allergies and finding a cure.

“I wish I didn’t have food allergies,” Brielle said, “but I don’t let them stop me from having fun. My mom prepares foods that look and taste as yummy as my family’s does, and my job is just to eat the foods I’m given. That’s OK, I still have a great life!”

For more information about FAAN or Sept. 20 fundraiser, visit www.foodallergywalk.org.

Amy Moellering welcomes stories about our local schools. Reach her at [email protected].

Originally published by Amy Moellering, MediaNews.

(c) 2008 Oakland Tribune. Provided by ProQuest LLC. All rights Reserved.

Rite Aid said today it is starting to reopen Gulf Coast stores impacted by Hurricane Gustav evacuations in Louisiana, Mississippi and Alabama. The company said it would work to open other Rite Aid stores temporarily closed as soon as possible. Stores may be closed because of local government mandatory evacuation.

A list of the 17 stores that have reopened follows. Some are open in the front end only; others are fully open, including the pharmacy. Customers and patients should check how much of an individual store is open. As some stores fall under local government curfews, customers should also check with the individual store for current operating hours. Store location information is available by calling 1-800-RITEAID (1-800-748-3243) and pressing “0” or by visiting www.riteaid.com. The Web site features a daily updated listing of open and closed Rite Aid stores in the hurricane-affected areas.

Rite Aid store #1784, 1971 Government Street, Mobile, AL (Store and pharmacy are open)

Rite Aid store #7342, 219 McArthur Road, Alexandria, LA (Store and pharmacy are open)

Rite Aid store #7301, 2016 N. Parkerson Avenue, Crowley, LA (Store and pharmacy are open, 5 p.m. curfew)

Rite Aid store #7298, 4510 Ambassador Caffery Parkway, Lafayette, LA (Store and pharmacy open, 3 p.m. curfew)

Rite Aid store #7296, 4710 Johnston St., Lafayette, LA (Store and pharmacy open, 6 p.m. curfew)

Rite Aid store #7238, 800 Metairie Road, Suite D, Metairie, LA (Store and pharmacy are open)

Rite Aid store #7344, 601 Keyser Avenue, Natchitoches, LA (Store and pharmacy are open)

Rite Aid store #7230, 820 Brookway Blvd, Brookhaven, MS (Store and pharmacy are open)

Rite Aid store #7226, 4031 Popps Ferry Road Suite A, Diberville, MS (Store and pharmacy are open)

Rite Aid store #7223, 11279 Highway 49, Gulfport, MS (Store and pharmacy are open)

Rite Aid store #7218, 4400 W. Hardy Street, Hattiesburg, MS (Store and pharmacy are open)

Rite Aid store #7227, 200 West Railroad St., Suite B, Long Beach, MS (Store open, pharmacy closed)

Rite Aid store #7209, 1703 Delaware Avenue, McComb, MS (Store and pharmacy are open)

Rite Aid store #7381, 285 Serqeant Prentiss Drive, Natchez, MS (Store and pharmacy are open)

Rite Aid store #7228, 3082 Bienville Blvd., Ocean Springs, MS (Store open, pharmacy closed)

Rite Aid store #7222, 416 Memorial Boulevard, Picayune, MS (Store open, pharmacy closed)

Rite Aid store #7231, 403 Highway 90, Waveland, MS (Store open, pharmacy closed)

Rite Aid will open other stores as soon as possible. Tractor trailer trucks loaded with extra supplies are waiting outside affected areas for safe delivery and to determine most immediate need. Extra generators and diesel fuel to run them also are waiting to be delivered as stores can open in areas without power. Hundreds of Rite Aid associates from other areas including pharmacists are on standby to assist with the expected demand. Assessments will be made for mobile units and additional storefronts that may be used when the full effect of the storm is known. The company is ready to take the same steps for Tropical Storm Hanna as it did with Hurricane Gustav.

Residents displaced by the Hurricane can visit any open Rite Aid in any city in any state for their prescriptions because the company’s satellite-linked computer network assures a complete customer prescription history at any Rite Aid store. Because of the state of emergency, Rite Aid pharmacies also can access prescription information for patients who do not normally get their prescriptions at Rite Aid.

Rite Aid Makes $75,000 Donation to The American Red Cross

Rite Aid also has made a $75,000 donation to The American Red Cross to help the victims, families and communities affected by Hurricane Gustav and is working with The American Red Cross to assess specific needs for other donations of supplies.

“Our hearts go out to the victims, families and communities affected by Hurricane Gustav. I am also very appreciative of all our pharmacists and other associates that have worked so hard to keep our stores open and will be reopening stores as soon as that can be done safely,” said Mary Sammons, Rite Aid chairman, president and CEO. “We are hoping that our donation to The American Red Cross can help make it just a little easier for those who have been impacted the most.”

Rite Aid Corporation (NYSE:RAD) is one of the nation’s leading drugstore chains with approximately 5,000 stores in 31 states and the District of Columbia with fiscal 2008 annual sales of more than $24.3 billion. Information about Rite Aid, including corporate background and press releases, is available through the company’s website at http://www.riteaid.com.

WellCare Health Plans, Inc. (NYSE: WCG) today announced that Rex M. Adams has joined the Company as chief operating officer. In this newly created position, Mr. Adams will report directly to the president and chief executive officer and have responsibility for the Company’s operating activities, including claims payment, customer service and information systems.

“WellCare is committed to optimizing its operations with an emphasis on efficacy and efficiency,” said Rex Adams. “I’m excited about the opportunity to work with and learn from WellCare’s talented team.”

“Rex has extensive executive management experience with a proven track record of performance improvement in complex operating environments such as ours,” said Heath Schiesser, president and chief executive officer of WellCare. “Although relatively new to our industry, his demonstrated ability to drive operating initiatives along with our current team’s deep industry expertise will be invaluable to us as we strive to be the leader in government sponsored health plans.”

Before joining WellCare, Mr. Adams served as the president and chief executive officer of AT&T East, a division of AT&T Inc. (NYSE: T). As one of five regional presidents, he was responsible for consumer and business sales and service as well as network operations for the Southern New England Telephone territory.

Mr. Adams joined AT&T following its merger with BellSouth Corporation. During his 12 years of service at BellSouth, he progressed through a number of leadership positions, including president of BellSouth Long Distance during its entry and rapid growth into the competitive long distance industry, and president of Wholesale Services during its implementation of government mandated and monitored operations for competitive local exchange and long distance carriers. He also served in leadership roles as part of Information Technology, Product Development and Management and Corporate Planning and Development.

Prior to joining BellSouth in 1994, Mr. Adams was a consultant at Monitor Company, a strategy-consulting firm that was founded by Harvard Business School professor Michael Porter. While at Monitor Company, Mr. Adams was involved with clients in a number of industries, focusing on cost optimization, process improvements and competitive positioning. He also spent five years in the Unites States Army as an infantry officer, where he was airborne, ranger and air assault.

Mr. Adams is a graduate of the Harvard Business School and the United States Military Academy at West Point. He currently sits on the Board of Trustees for the Yale-New Haven Hospital, one of the nation’s premier teaching and research hospitals.

About WellCare Health Plans, Inc.

WellCare Health Plans, Inc. provides managed care services exclusively for government-sponsored healthcare programs, focusing on Medicaid and Medicare. Headquartered in Tampa, Florida, WellCare offers a variety of health plans for families, children, the aged, blind and disabled and prescription drug plans, currently serving more than 2.5 million members nationwide. For more information about WellCare, please visit the Company’s website at www.wellcare.com.