A Vitamin Could Alleviate Chronic, Progressive Multiple Sclerosis

Researchers have found a possible way to protect people with multiple sclerosis (MS) from severe long-term disability: increase nervous-system levels of a vital compound, called nicotinamide adenine dinucleotide (NAD), by giving its chemical precursor – nicotinamide, a form of vitamin B3.

Current therapies for MS mainly address the relapsing-remitting phase of the disease, but some of these have severe side effects, and most patients eventually enter a chronic progressive phase for which there is no good treatment. Using a mouse model of MS, researchers in the Neurobiology Program at Children’s Hospital Boston found strong evidence that nicotinamide may protect against nerve damage in the chronic progressive phase, when the most serious disabilities occur. Their findings appear in a cover article in the September 20 Journal of Neuroscience.

MS is a neurologic disorder in which nerve fibers, or axons, are damaged through inflammation, loss of their insulating myelin coating, and degeneration. This damage disrupts nerves’ ability to conduct electrical impulses to and from the brain, causing such symptoms as fatigue, difficulty walking, pain, spasticity, and emotional and cognitive changes. Current treatments mainly protect against inflammation and myelin loss, but do not completely prevent long-term axon damage.

A team led by Shinjiro Kaneko, MD, a research fellow at Children’s, and senior investigator Zhigang He, PhD, also from Children’s, worked with mice that had an MS-like disease called experimental autoimmune encephalitis (EAE). Through careful experiments, they showed that nicotinamide protected the animals’ axons from degeneration – not only preventing axon inflammation and myelin loss, but also protecting axons that had already lost their myelin from further degradation.

Intriguingly, mice with EAE who received daily nicotinamide injections under their skin had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treatment. The greater the dose of nicotinamide, the greater the protective effect.

On a scale of 1 to 5 (1 indicating mild weakness only in the tail, 4 indicating paralysis involving all four limbs, and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4. All differences between treated groups and controls were statistically significant.

Mice with the greatest neurologic deficits had the lowest levels of NAD in their spinal cord, and those with the mildest deficits had the highest NAD levels. Mice that had higher levels of an enzyme that converts nicotinamide to NAD (known as Wlds mice) responded best to treatment.

Moreover, nicotinamide significantly reduced neurologic deficits even when treatment was delayed until 10 days after the induction of EAE, raising hope that it will also be effective in the later stages of MS. “The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage,” says Kaneko.

In other experiments, the researchers demonstrated that nicotinamide works by increasing levels of NAD in the spinal cord and that NAD levels decrease when axons degenerate. Finally, they showed that giving NAD directly also prevented axon degeneration.

NAD is used extensively by cells to produce energy through the breakdown of carbohydrates. Its chemical precursor, nicotinamide, has several characteristics that make it a promising therapeutic agent: it readily crosses the blood-brain barrier, is inexpensive and available in any drugstore, and its close relative, vitamin B3, is already used clinically to treat pellagra (vitamin B3 deficiency), high cholesterol, and other disorders. Although nicotinamide is thought to have few side effects, the doses used in mice would translate to much higher human doses than are normally used clinically, so would need to be tested for safety.

“We hope that our work will initiate a clinical trial, and that nicotinamide could be used in real patients,” Kaneko says. “In the early phase of MS, anti-inflammatory drugs may work, but long-term you need to protect against axonal damage.”

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The research was funded by the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke.

Children’s Hospital Boston is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Children’s research community. Founded as a 20-bed hospital for children, Children’s Hospital Boston today is a 347-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children’s also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: childrenshospital/newsroom.

Contact: James Newton

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Cook Medical Receives FDA Approval To Market Improved Zenith(R) AAA Iliac Flex Legs And Z-Trak(TM) Introduction System

Further innovating the field of advanced aortic disease repair technologies, Cook Medical announced approval from the U.S. Food and Drug Administration (FDA) to market its improved Zenith Abdominal Aortic Aneurysm (AAA) Iliac Flex Legs and Z-Trak Introduction System, made for use with the Zenith Flex AAA Endovascular Graft. The products are designed specifically to provide increased flexibility and improved conformability in the aorta and iliac artery, a tortuous section of patient anatomy, for patients undergoing endovascular aneurysm repair (EVAR).

The Zenith AAA Flex Leg external stents are shorter than those of Cook Medical’s previous offering, with increased gaps between the stents. This design improves flexibility and conformability, reducing the potential of the leg to kink. The device, like the Zenith Flex main body, is constructed of polyester graft material supported by stainless steel Z-stent bodies. The Zenith Flex endograft main body with Flex Leg stents represents an important engineering achievement in the pursuit of improved outcomes for patients undergoing EVAR.

Cook’s revolutionary Z-Trak Introduction System provides an integrated interface to Cook’s market-leading device, continuing its established maneuverability for precise, controllable device orientation and deployment of the company’s endovascular stent graft. Precision is key to this system, allowing the operator to make last-minute adjustments prior to deployment of the stent graft, affording physicians the ability to achieve highly accurate placement. The trigger-wire delivery mechanism allows adjustment of the endograft in a semi-deployed state for pinpoint accuracy.

“FDA approval of the Z-Trak Introduction System and Zenith AAA Flex Leg brings the flexibility and deliverability of our market-leading AAA platform to U.S. physicians and their patients,” said Phil Nowell, global director of Cook’s Aortic Intervention strategic business unit. “Our commitment to creating innovative devices and technology to help physicians perform minimally invasive diagnostic and therapeutic procedures for aortic aneurysms that improve patient outcomes and make the benefits of EVAR available to an ever-widening cohort of patients is revolutionizing the industry and creating a new gold standard for the treatment of this life-threatening disease.”

Post-operative and post-discharge recovery times are typically shorter with EVAR which may help patients return to their normal lifestyle routines far faster than for those who undergo open surgery.

Availability

The Cook Zenith AAA Flex Leg and Z-Trak Introduction System are available in the United States as well as in continental Europe and the United Kingdom.

About Cook Medical

Cook Medical was one of the first companies to help popularize interventional medicine, pioneering many of the devices now commonly used worldwide to perform minimally invasive medical procedures. Today, the company integrates device design, biopharma, gene and cell therapy and biotech to enhance patient safety and improve clinical outcomes in the fields of aortic intervention; interventional cardiology; critical care medicine; gastroenterology; radiology, peripheral vascular, bone access and oncology; surgery and soft tissue repair; urology; and assisted reproductive technology, gynecology and high-risk obstetrics. Cook is a past winner of the prestigious Medical Device Manufacturer of the Year Award from Medical Device & Diagnostic Industry magazine.

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Combined Minimally Invasive Procedures Offer New Option For Lumbar Degenerative Scoliosis

Surgeons at Cedars-Sinai Medical Center’s Institute for Spinal Disorders have combined three innovative minimally invasive spine surgery procedures to treat spinal curvature in adults, a common consequence of aging. An article in the October issue of the Journal of Spinal Disorders and Techniques is believed to be the first to document the use of these procedures in combination to correct this condition, known as adult lumbar degenerative scoliosis.

“Many patients suffering from degenerative scoliosis are elderly and have coexisting medical problems that make them poor candidates for traditional surgery and a long recovery process. But as a result of three new technologies and minimally invasive approaches, we are able to offer patients who otherwise might not be candidates for surgery, a solution that is safe and provides very good results,” said orthopaedic surgeon Neel Anand, M.D., Mch. Orth, director of Orthopaedic Spine Surgery at Cedars-Sinai.

Anand said lumbar degeneration and curvature can be caused simply by the wear and tear of aging. Discs the cushions and spacers between vertebrae wear down and collapse, allowing the spine to shift out of alignment. In other cases, minor scoliosis that may have existed since childhood becomes more pronounced with age. In either situation, pain is the primary complaint.

The article reviews 12 cases of Anand’s. These cases were examined as part of a retrospective chart review for patients who underwent these techniques as part of standard care. Patients were 50 to 85 years old, with an average age of about 73. Each had undergone extensive conservative treatment, such as medical management and physical therapy, without long-term success. Curvature resulted from the degeneration of multiple discs, ranging from two to eight segments of the spine.

The first stage of the two- to three-step correction procedure was performed through small incisions in the patient’s side, working through a tube to access the front of the spine. Using either of two systems the XLIF® (Extreme Lateral Interbody Fusion) or the DLIF® (Direct Lateral Interbody Fusion) Anand cleared out damaged disc material and replaced it with spacers filled with bone and a protein that promotes fusion.

“We used to access the front of the spine through the abdomen. The biggest advantage of going in from the side is that we no longer have to work around the organs and large blood vessels of the abdomen. We work through a very safe corridor to get to the discs in question. We go in and correct each disc that has collapsed, like building a skyscraper. As we put in spacers from the bottom up, we get considerable correction, just from doing the lateral approach, the first stage,” Anand said.

The second step was needed only for patients whose scoliosis affected the area between the lower end of the lumbar spine and the top of the sacral spine (the lumbar 5 and sacral 1 vertebrae), which cannot be accessed from the side because of the location of the pelvic bone. In these cases, the area was accessed from below, using the AxiaLIF® procedure, which allows the L5-S1 disc to be secured with a solid, sturdy screw.

The final stage, performed two or three days after the first, was the placement of rods on either side of the spine. This was accomplished with the use of the CD Horizon Longitude system and special high-tech screws.

“The third technology making this correction possible for these patients is the percutaneous screw that can be placed through small nicks in the skin. Using fluoroscopic guidance, we’re able to place the screws into the vertebral bodies and pass the rods through the skin into position. We then connect the rods to the screws and get further correction of the curve,” Anand said.

Anand, first author of the journal article, is a paid consultant with the three companies that market the instrumentation and techniques. Because he was involved in the development of the percutaneous screws, he receives royalties from the manufacturer when the devices are used elsewhere, but he receives no royalties on any cases performed at Cedars-Sinai.

“With traditional surgical procedures and large incisions, patients would have to spend time after surgery in the intensive care unit for monitoring and blood transfusions, and there would be months of recuperation,” said Anand. “With the new technologies and minimally invasive techniques, we lose very little blood and patients are back on a regular surgical nursing unit in about an hour. And instead of going through six months or more of painful, restricted recuperation, recovery time is much shorter and more comfortable. We’re achieving the same correction but through different, smaller, safer portals of entry.”

Citation: Journal of Spinal Disorders and Techniques, October 2008, Vol.21, No.7: “Minimally Invasive Multilevel Percutaneous Correction and Fusion for Adult Lumbar Degenerative Scoliosis: A Technique and Feasibility Study.”

Cedars-Sinai Medical Center
8700 Beverly Blvd., Rm. 2429A
Los Angeles, CA 90048
United States
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1,000 Nurses Call On Congress To Act Now On Patient Safety – California Nurses Association

More than 1,000 registered nurses from across the country rallied in Washington DC Wednesday, raising an unprecedented, unified voice for patient safety reforms and new, national standards for patient care conditions and standards for nurses.

The event was sponsored by the nation’s largest nurses’ union and professional association, the 155,000-member National Nurses United, which came to Washington to press the case for quality of care legislation that was not part of the national healthcare bill enacted earlier this year, and to build on the unity of RNs who are NNU members from coast to coast.

In addition to a march, rally, and conference, the RNs visited nearly 100 members of Congress, prodding legislators to work on the unfinished business of healthcare reform, quality of care and patient safety. The actions coincided with National Nurses Week.

Noting recent national attention on the West Virginia mining disaster and the Gulf Coast oil spill, NNU Co-President Jean Ross, RN said that “similar accidents happen every day away from the media spotlight in U.S. hospitals and other healthcare settings. It’s time to act to protect our patients and our communities.”

“We’re the voice of not only nurses but patients across the country,” said NNU Co-President Karen Higgins, RN. “When we leave this room I want everyone to remember that. When it comes time to make decisions about healthcare and people say ‘leave it to the experts,’ tell them ‘I am the expert.’ “

Among the legislative solutions are S 1031/HR 2133 that would, among other components, establish minimum ratios of nurses to patients for all U.S. hospitals, modeled after a successful California law, and S 1788/HR 2381 which would also promote nurse retention and reduce patient accidents and injuries by establishing safe patient lifting and handling policies.

Sen. Al Franken of Minnesota, author of S 1788, hosted a hearing on the bill Tuesday at which several nurses on hand for the week cited experiences that demonstrated the need for the bill.

Speaking Wednesday to an NNU rally across from the Capitol, Franken told the RNs, “You are the ones we look to for advice, comfort, expertise and care. You are tireless advocates for the country’s well-being. You’re the ones we trust to care for our loved ones, that’s what your expertise is, and it’s simply unacceptable that you’re putting your own health on the line to care for patients.”

“Now it’s time to make sure that all nurses in all states have access to a safe workplace. One injured nurse is one too many. Employers have a fundamental obligation to put in place a safe working environment for all workers and nurses are no exception,” Franken said.

Rep. Lynn Woolsey of California, speaking to the nurses, also emphasized why the bill is needed, “We don’t need to create another patient in the process of caring for one.”

U.S. Labor Secretary Hilda Solis, who also addressed the conference, told the nurses that more than 36,000 health care workers were injured by lifting and transferring patients, according to 2008 Bureau of Labor Statistics data. In addition, she said, 12 percent of nurses who plan to leave the profession cited back injuries as a contributing factor.

“What a waste when the career of an experienced nurse is ended years or decades too early because of an easily preventable back injury,” Solis said. “In these days of ever-rising health care costs, what a waste of money to pay workers compensation and disability for easily preventable back injuries.”

S 1031 author Sen. Barbara Boxer of California and HR 2133 author Rep. Jan Schakowsky of Illinois also spoke the NNU event about the ratio legislation which, according to a groundbreaking study from the University of Pennsylvania released last month, could have cut post-surgical patient deaths by 14 percent in New Jersey and 11 percent in Pennsylvania, two comparable states the researchers compared to California.

“We know that nurse-to-patient ratios work, and it is time to enact them around the nation. California was the testing ground and it’s working,” Boxer said. “Too often you are overworked because of staffing levels that are inadequate and that is unacceptable.”

The Penn study, from noted researcher Linda Aiken, RN, PhD, documents “what California nurses have seen every day at the bedside since passage of the law — safer care conditions, an enhanced quality of life for patients, and, as an added bonus, reduced burnout for nurses which mitigates the nursing shortage,” said California RN and NNU co-president Deborah Burger.

NNU is also seeking passage of HR 949/S 362 to restore equal collective bargaining rights for Veterans Affairs nurses.

Strengthening the rights of direct care RNs and their ability to more effectively advocate for patients and their colleagues, was another major theme of the NNU gathering.

“We’ve got to say something in a united way that tells employers it’s a new day in America and RNs are going to stand up and not take it anymore,” NNU Executive Director Rose Ann DeMoro said.

The RNs unanimously endorsed a resolution to establish national collective bargaining standards that notes the growing attack by many hospital employers against nurses and patient safety conditions.

The resolution notes that NNU will oppose “concessionary agreements that are injurious to our patients, our members, and our profession that undermine all represented RN contract standards” that include reductions in health coverage, pensions and other retirement security, two-tier programs for new hires, and reductions that impair patient safety.

Additionally, the resolution pledges NNU to fight for enhanced RN staffing and other improvements in patient care standards, improved retirement security for RNs, limits on the introduction of new technology that displaces RNs or RN professional judgment, and additional workplace safety measures.

Source
California Nurses Association Continue reading

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ATS Medical Announces Regulatory Approval Of The ATS Open Pivot AP360 Mechanical Heart Valve In Japan

ATS Medical, Inc. (Nasdaq: ATSI), manufacturer and marketer of state-of-the-art cardiac surgery products and services, announced the Japanese Ministry of Health, Labor and Welfare has approved commercial distribution of the ATS Open Pivot(R) AP360(TM) Mechanical Heart Valve.

The ATS AP360 heart valve maximizes hemodynamic performance with a new supra-annular cuff design that facilitates implantation. The original ATS Medical Open Pivot(R) Heart Valve is highly regarded for fundamental design features that promote best-in-class hemodynamic performance, enhanced resistance to blood clot formation and improved patient quality of life through quieter valve operation. In a response to the highly individualized and specific valve selection criteria of cardiac surgeons, particularly with respect to implantability, the ATS AP360 combines proven performance with a cuff design that extends its appeal to a broader spectrum of surgeons.

“Our long time distribution partner, Century Medical, Inc., worked diligently to facilitate this important approval in conjunction with the ATS Quality and Regulatory Organization. The cuff design of the ATS AP360 valve provides significant hemodynamic benefit for patients with a small aortic root and will be ideal for the unique needs of the Japanese market,” said Michael Dale, President and CEO of ATS Medical. “The newly approved AP360 will provide even more opportunity to further penetrate the Japanese marketplace.”

About ATS Medical

ATS Medical, Inc. is dedicated to ‘Advancing The Standards’ of cardiac surgery through the development, manufacturing and marketing of innovative products and services for the treatment of structural heart disease. ATS Medical serves the cardiac surgery community by focusing on two distinct but operationally synergistic market segments: heart valve disease therapy and surgical ablation of cardiac arrhythmias.

ATS was originally founded to develop the ATS Open Pivot(R) Heart Valve as a new mechanical heart valve standard of care. Today the Open Pivot heart valve is the preferred mechanical heart valve in many markets around the world and the fastest growing mechanical prosthesis in the market. Building on this legacy and addressing the largest market segment in heart valve therapy, the ATS 3f(R) brand encompasses an innovative tissue heart valve portfolio to address conventional open surgery requirements as well as the growing demand for less invasive, sutureless based procedures. The ATS 3f(R) portfolio includes offerings at various stages including early product development, pivotal clinical trials, and market commercialization. Completing the portfolio in heart valve therapy is the ATS Simulus(R) annuloplasty product line. Simulus products assist the surgeon in repairing a patient’s native heart valve as an alternative to replacement. Continuing ATS Medical’s focus on serving the cardiac surgery community are the ATS CryoMaze(TM) products for surgical cryoablation of cardiac arrhythmias. ATS CryoMaze(TM) products are used by surgeons to treat patients suffering from cardiac arrhythmias, the largest and fastest growing form of structural heart disease in populations over 60 years of age.

Safe Harbor

This Press Release contains forward-looking statements that may include statements regarding intent, belief or current expectations of the Company and its management. Actual results could differ materially from those projected in the forward-looking statements as a result of a number of important factors, including the results of clinical trials, the timing of regulatory approvals, the integration of 3f Therapeutics and the surgical cryoablation business of CryoCath Technologies, Inc., regulatory actions, competition, pricing pressures, supplier actions and management of growth. For a discussion of these and other risks and uncertainties that could affect the Company’s activities and results, please refer to the Company’s filings with the Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2008.

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American College Of Physicians Tells President Obama And Congress Of The Urgent Need To Move Forward On Essential Reforms

“The unfortunate truth is that by many measures, the State of America’s health care is in decline,” Joseph W. Stubbs, MD, FACP, president of the American College of Physicians (ACP), reported at ACP’s annual State of the Nation’s Health Care briefing. “We have too many uninsured, too few primary care physicians, and the cost of health care is rising faster than we can afford.”

“Health care in the United States is facing an unprecedented challenge of affordability and sustainability,” continued Dr. Stubbs. “Yet a highly-partisan and polarized debate over health care reform legislation regrettably has taken the country’s ‘eye off the ball’ – from the urgency of implementing reforms.”

In its report, ACP detailed the dire consequences the country would face if Congress and the President failed to enact comprehensive health care reform.

“For decades, we have seen Washington politicians decide that health care reform is too hard, and we may be on the brink of seeing this happen once again,” observed Bob Doherty, ACP’s Senior Vice President of Governmental Affairs and Public Policy. “But this time, we know what the consequences will be. Affordable health care will be out of reach for many middle class families. One out of five of us will be uninsured. We won’t be able to find a primary care doctor. And increased Medicare and Medicaid spending will create an unprecedented fiscal and budget crisis.”

As a path for moving forward on health care reform ACP recommended that:
Congress and the President reach an agreement on a legislative pathway to enact a final bill and builds upon – and improves upon – the bills already passed by both houses of Congress;

President Obama should reach out to both Republican and Democratic members of Congress to develop bipartisan proposals to reduce the costs associated with the medical liability tort system, and to work together on other issues that have support across the political parties, such as increasing the numbers of primary care physicians;

Congress should give preferred funding for discretionary programs to advance the goals of expanding coverage, ensure a sufficient supply of primary care physicians, and encourage testing and dissemination of models to improve health care delivery;

Congress must permanently end the cycle of Medicare physician payment cuts caused by the Sustainable Growth Rate (SGR) formula; and,

President Obama should use his executive authority to require that all health-related federal agencies and private sector contractors develop plans to increase the numbers of primary care physicians and reduce the time that clinicians and patients spend on health plan administration.

“The alternative to moving forward on comprehensive health reform is an unconscionable abdication of responsibility by our elected leaders to ensure that high quality health care remains available and affordable for American families today, tomorrow and for years to come,” concluded Dr. Stubbs.

Source:
David Kinsman
American College of Physicians Continue reading

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Cook Medical Launches Spectrum Glide To Combat Catheter Related Bloodstream Infections

Cook Medical announces the general availability in Europe of Cook Spectrum® Glide™ Minocycline/Rifampin Impregnated Catheters. Spectrum, created by Cook’s Critical Care strategic business unit, has been specifically designed to provide the best protection against catheter-related bloodstream infections (CRBSIs), which according to the Department of Health (DoH) cost the NHS upwards of ВЈ6,209 per infected patient in 2003 alone.

Catheters are currently either untreated or surface-treated with a combination of compounds which are intended to endow those catheters with some antiseptic qualities. Both technologies have been shown clinically to be less effective than Spectrum antimicrobial catheters, which are impregnated on both sides with a combination of rifampin and minocycline.

Spectrum catheters are impregnated with rifampin and minocycline on the external and internal surfaces to provide protection against catheter-related bloodstream infections, via broad-spectrum activity against gram positive and gram negative organisms. This protection against CRBSIs lasts for at least two weeks and clinical trials in the US have found no occurrence of antibiotic resistance.

Dr Duncan Wyncoll, Consultant Intensivist at Guy’s and St Thomas’s Hospital in Westminster London, comments: “The NHS as a whole is taking great strides to reduce hospital acquired infections by adopting a variety of measures, including the adoption of innovative technology. The Cook Spectrum catheter is one such example of this technology. The next step is to hone the techniques used to place the catheters in an effective manner. Reducing physician error in catheter placement will drive infection rates down still further.”

How Does Spectrum Work?

All catheter tube extensions are labelled with port name, gage size and flush volume. Cook Medical’s Spectrum is available as a double or triple lumen catheter. Lumens should be pre-flushed prior to use and the catheters’ hydrophilic coating activates upon insertion into the vessel. Spectrum incorporates either two or three separate, non-communicating vascular access lumens within a single catheter body. This design reduces the need for multiple venipunctures or multiple stopcock configurations with single lumen catheters which may increase the likelihood that any individual catheter may become infected. Exit ports of individual lumens are separated by an appropriate distance in proportion to the catheter’s French size – Spectrum comes in French sizes 4.0, 5.0 and 7.0.

Bruce Gingles, Global Vice President of Cook Medical’s Critical Care strategic business unit, says: “Healthcare-associated infections and catheter-related bloodstream infections receive ever more attention from the media, politicians, patients and physicians. The UK’s National Audit Office states that hospital-acquired infections can be reduced by around 15 per cent across the NHS through better management and control. We believe medical technology has a large part to play in this battle.

“We are working with an increasing number of surgeons and healthcare professionals within institutions who are successfully driving down infection rates through a heightened appreciation of the risks involved with incomplete infection control. Efforts to beat CRBSIs must come from a platform of prevention, not just cure. This is precisely why we’ve designed the Spectrum Glide catheter.”

About Cook Medical

Cook Medical was one of the first companies to introduce interventional devices in the United States. Today, the company participates in all global markets, integrating device design, biopharma, gene and cell therapy and biotechnology to enhance patient safety and improve clinical outcomes. Cook won the prestigious Medical Device Manufacturer from Medical Device and Diagnostic Magazine.

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