Pfizer And Auxilium Announce Commencement Of European Regulatory Review Of XIAFLEXTM For The Treatment Of Dupuytren's Contracture

Pfizer Inc. (NYSE: PFE) and Auxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) announced that Pfizer received notification from the European Medicines Agency that the Marketing Authorization Application (MAA) for XIAFLEX™ (collagenase clostridium histolyticum), a novel, first-in-class, biologic for the treatment of Dupuytren's contracture (a condition resulting in the contracture of the fingers into the palm), has completed the validation phase successfully. As a result, the scientific/technical review procedure commenced on 21 January 2010.


"We are pleased to partner with Auxilium to bring forward what potentially could be the first approved pharmaceutical treatment option for patients suffering with Dupuytren's contracture, a condition which can significantly impact patients' ability to perform everyday tasks with their hands and therefore impacts quality of life," said Michael Berelowitz, M.D., senior vice president, Clinical Development and Medical Affairs, Pfizer Specialty Care Business Unit. "XIAFLEX, if approved, will be an important addition to the Specialty Care Business Unit's portfolio of medicines in Europe designed to offer true clinical value to patients and healthcare providers who need them."


Armando Anido, Chief Executive Officer and President of Auxilium said, "We believe that commencement of the regulatory review procedure is a notable milestone in our effort to bring the first approved minimally-invasive, nonsurgical treatment option to Dupuytren's contracture patients in Europe. We look forward to working with our partner Pfizer as the EU regulatory review process for the product moves forward."


Based on the completion of the validation phase and today's confirmation from the European Medicines Agency of the start of the regulatory review procedure, Auxilium will receive a $15 million milestone payment from Pfizer.


Under the terms of the strategic alliance agreement between Pfizer and Auxilium, Pfizer will receive exclusive rights to commercialize XIAFLEX in the 27 member countries of the European Union (EU) and 19 other European and Eurasian countries. In addition, Pfizer will be primarily responsible for regulatory activities for XIAFLEX in these countries.


About Dupuytren's Contracture


Dupuytren's contracture is a condition that affects the connective tissue that lies beneath the skin in the palm. The disease is progressive in nature. Typically, nodules develop in the palm as collagen deposits accumulate. As the disease progresses, the collagen deposits form a cord that stretches from the palm of the hand to the base of the finger. Once this cord develops, the patient's fingers contract and the function of the hand is impaired. Currently, surgery is the only effective treatment. The incidence of Dupuytren's disease, inclusive of pits, nodules and cords, is highest in Caucasians, historically those of Northern European descent, with a global prevalence of three to six percent of the Caucasian population. Most cases of Dupuytren's contracture occur in patients older than 50 years and a hereditary component exists in approximately 40% of patients.


The most frequently affected parts of the hand associated with Dupuytren's contracture are the joints called the Metacarpal-Phalangeal Joint, or MP joint, which is the joint closest to the palm of the hand and the Proximal Intra-Phalangeal Joint, or the PIP joint, which is the middle joint in the finger. The little finger and ring finger are most frequently involved and about half of patients have bilateral disease. There are currently no drugs approved by the U.S. Food and Drug Administration or in the European Union for the treatment of Dupuytren's contracture, which is treated primarily by an open surgical procedure.


Source

Pfizer Inc.
Auxilium Pharmaceuticals, Inc.

Final Draft Guidance Recommends Osteoporosis Treatment As A New Option For Women At Increased Risk Of Fractures

Postmenopausal women who are at increased risk[1] of osteoporotic fractures should be treated with denosumab if treatment with the currently available oral bisphosphonates alendronate, and either risedronate or etidronate is unsuitable, according to draft guidance published today (Wednesday 15 September) by NICE.


Denosumab (Prolia, Amgen) is licensed to treat postmenopausal women at increased risk of osteoporotic fractures. It is given by injection twice a year and works by reducing bone breakdown and increasing bone mass and strength.


Most postmenopausal women at increased risk of osteoporotic fractures are treated with oral bisphosphonates, but for some women these drugs may be unsuitable. Reasons for unsuitability are that a woman is unable to comply with the special instructions for the administration of oral bisphosphonates (for instance she may not be able to remain standing or sitting upright for half an hour after taking the drugs), or has a contraindication to, or is intolerant of bisphosphonates. Denosumab should be one of the options for these women if they are judged to be at increased risk of fractures, according to the draft NICE guidance.


Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said: "Our independent Appraisal Committee felt that there was good quality evidence to show that denosumab is a useful addition to the treatment options available for women who can't have oral bisphosphonates. It should help to prevent a first fracture in women at increased risk and also help prevent further fractures in women who have already experienced one. We believe that older women at increased risk of osteoporotic fractures who cannot take alendronate, and either risedronate and etidronate should be considered for this drug alongside the other options available in order to help prevent the misery of breaking a bone."


Consultees now have until 29 September to appeal against the recommendations via the NICE website. NICE has not yet issued final guidance to the NHS; these decisions may change after appeal. Final guidance is expected to be published later this year. Until then, NHS bodies should make decisions locally on the funding of specific treatments.


About the guidance


- View the final appraisal determination (FAD) on Osteoporotic fractures - denosumab from Wednesday 15 September 2010. NICE expects to publish final guidance on denosumab later this year.


- The final appraisal determination states:


1.1 Denosumab is recommended as a treatment option for the primary prevention of osteoporotic fragility fractures only in postmenopausal women at increased risk of fractures:















- who are unable to comply with the special instructions for administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments and


- who also have a combination of T-score[2], age and number of independent clinical risk factors for fracture (see section 1.3)


1.2 Denosumab is recommended as a treatment option for the secondary prevention of osteoporotic fragility fractures only in postmenopausal women at increased risk of fractures who are unable to comply with the special instructions for administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments


1.3 For the purposes of this guidance, independent clinical risk factors for fracture are parental history of hip fracture, alcohol intake of 4 or more units per day, and rheumatoid arthritis.


1.4 People currently receiving denosumab for the primary or secondary prevention of osteoporotic fragility fractures who do not meet the criteria specified in recommendations 1.1 or 1.2 should have the option to continue treatment until they or their clinician consider it appropriate to stop.


- Denosumab is administered as a single subcutaneous injection into the thigh, abdomen or the back of the arm. The recommended dosage is 60mg once every six months.


- Each dose costs ВЈ183, which means that the annual cost of treatment with denosumab is ВЈ366. Costs may vary in different settings because of negotiated procurement discounts.


[1]' Increased risk' is defined by a combination of low bone mineral density, age and a number of other clinical risk factors such as parental history of hip fracture, high alcohol intake and rheumatoid arthritis.


[2] T-score relates to the measurement of bone mineral density (BMD) using central (hip and/or spine) double-energy x-ray (DXA) scanning, and is expressed as the number of standard deviations (SD) below peak BMD.


Source:

NICE


View drug information on Prolia.

Lessons From Guinea Fowl On Avoiding Falls

Biomechanics researchers Timothy Higham of Clemson University and Andrew Clark of the College of Charleston conclude that moving quickly in a forward, firm-footed stance across a slippery surface is less likely to lead to a fall than if you move slowly. Approaching a slippery surface slowly hinders the necessary task of shifting the center of mass forward once foot contact is made.



The researchers studied helmeted guinea fowl strutting along a six-meter runway that either had a rough-surface section (150-grit sandpaper) or a slippery one (polypropylene shelf liner). High-speed video recorded the action. The experiment is reported in the Journal of Experimental Biology, "Slipping, sliding and stability: locomotor strategies for overcoming low-friction surfaces," pages 1369-1378 (vol. 214).



Helmeted guinea fowl react to slips much in the same way humans do, making them good test subjects, according to Higham. He and Clark are interested in how animals move and avoid injury when making their way through their environments.



Finding out how animals can respond rapidly to unexpected changes in their habitat, the scientists' stated that their research would "ultimately yield important information regarding the flexibility of physiological and behavioral systems," according to their article.



"The findings can be useful in helping humans, especially older ones, make their way across surfaces that are wet, icy or oily," said Higham. "The key to avoiding slips seems to be speed and keeping the body mass forward, slightly ahead of the ankles after the foot contacts the ground."



Slips are a major cause of falls that can cause injuries and even deaths. Slips accounted for about 44 percent of fatal and nonfatal work-related falls, according to a U.S. Bureau of Labor Statics report in 1992.



Clark and Higham not only saw that speed, foot position and body alignment made a difference, but also the slip distance. For a guinea fowl to fall, it needed to slip a minimum of 10 centimeters - just under four inches. The distance is the same for humans, said Higham.



Guinea fowl leg joints and human knees and ankles function in similar ways: the position of the knee relative to the foot can create joint angles - wide or narrow - that can cause or prevent loss of balance on slippery surfaces, the scientists said. Once the knee passes the ankle during contact with slippery ground, slipping stops.



"Our study shows that there are common limb-control strategies on slippery surfaces in helmeted guineas and humans," said Higham .



Source:

Timothy Higham

Clemson University

Vertebroplasty Heals Fractures But May Cause Others, Mayo Clinic Study Finds

A new Mayo Clinic study finds that vertebroplasty, a procedure used to treat painful compression fractures in the spinal vertebrae due to osteoporosis, appears to increase the risk for new fractures in adjacent vertebrae. The study also found vertebrae adjacent to fractures treated with vertebroplasty fracture significantly sooner than more distant vertebrae. Findings will be published in the January issue of American Journal of Neuroradiology (ajnr).


"We found there is a relationship between vertebroplasty and the development of new fractures," says Andrew Trout, first author of the paper describing the study's findings. "People should be made aware of the fact that despite the positive benefits of vertebroplasty, there is a risk of new fractures with this procedure."


The researchers discovered that following vertebroplasty, which involves injecting bone cement into the vertebrae to stabilize fractures, patients' risk for new fractures in vertebrae adjacent to those treated was 4.62 times the risk for nonadjacent vertebral fractures. In addition, they found that new fractures occurred in adjacent vertebrae sooner than in nonadjacent vertebrae: a median of 55 days following vertebroplasty for adjacent fractures and 127 days for nonadjacent vertebral fractures. This is the largest study ever to address the risk of new fractures post-vertebroplasty and the first study to examine whether there is a difference in time course between the development of new fractures adjacent and nonadjacent to the original fracture after treatment with vertebroplasty.


"Previous studies of vertebroplasty in cadavers and using computer simulation suggested that inserting cement in one bone weakens adjacent bones," explains David Kallmes, M.D., Mayo Clinic neuroradiologist and senior study investigator. The weakening effect is possible due to the overall cushioning effect of the spine, where stiffening one part puts greater stress on another, he says.


"Everyone involved in vertebroplasty research is concerned about the possibility that placement of cement into fractures will actually increase the risk of fractures in other bones nearby," says Dr. Kallmes. "Of course we do not want to cause new fractures by treating existing fractures, so we are studying treated patients to see if their bones are fracturing sooner or more frequently than would otherwise be expected."


Dr. Kallmes explains that though this study points to a significant association between vertebroplasty and new fractures occurring in adjacent vertebrae, it is not absolute proof of cause and effect.


"We consider the findings of the current study provocative," he says. "Our findings suggest vertebroplasty speeds -- and possibly facilitates -- the fracture of adjacent vertebrae. This is not definitive evidence, but should be considered when discussing risks with patients before embarking on vertebroplasty."















At this point in the research, Dr. Kallmes still practices vertebroplasty and believes the potential advantages outweigh the risks.


"I still have an open mind about the true risk of new fracture after vertebroplasty," he says. "Vertebroplasty most likely is a good procedure, and it is still probably prudent to help relieve pain with vertebroplasty. We need to be aware of potential long-term risks, however."


Dr. Kallmes recommends that patients considering vertebroplasty for unhealed vertebral fractures consider all potential risks with their physicians, including risks of new fractures in adjacent vertebrae, prior to undergoing the treatment.


The increased risk of adjacent vertebral fractures post-vertebroplasty in some patients could be due to throwing off the biomechanics of the spine by introducing cement, or it could relate to the especially weakened nature of the bones in some patients or the type of cement used in the procedure, say the researchers.


"It may be prudent to develop new cements that may be friendlier to the spine," says Dr. Kallmes. He also cites the importance of optimizing other aspects of care for osteoporotic patients, especially regarding drug therapies aimed at overall bone health.


This study involved a retrospective analysis of the risk and timing of subsequent fractures in 432 Mayo Clinic patients previously treated with vertebroplasty. From this group, 186 new fractures occurred post-vertebroplasty in 86 patients; 77 of the fractures were located in vertebrae adjacent to the vertebroplasty-treated vertebrae.


Vertebroplasty is used to treat patients with osteoporosis or a similar condition who have suffered compression of their spines with no or minimal injury. Osteoporotic patients can fracture their vertebrae with simple, everyday movements such as bending over to tie their shoes or turning over in bed, because their bones are weakened. Each year, 700,000 people suffer this injury. For four out of five patients, the fracture heals and the accompanying pain goes away in approximately four weeks with bed rest and analgesics. However, for the other one out of five patients, the fracture does not heal and the pain persists, requiring treatment. Surgery is not an option for these patients, as their bones are too weak. Vertebroplasty is the only available treatment option for patients in this condition. Vertebroplasty is not appropriate for patients with back pain due to ligament injuries, joint disease or narrowing of the spinal canal, says Dr. Kallmes.


For more on vertebroplasty, see
mayoclinic/vertebroplasty/index.html.


Lisa Lucier

newsbureaumayo

Mayo Clinic

mayoclinic/news

Inflammation Clue To Fragile Bones In Muscular Dystrophy

Inflammation could contribute to bone loss in Duchenne's muscular dystrophy (DMD), a discovery made by a group of Italian researchers. Dr Anna Rufo and her colleagues found that levels of an inflammatory molecule, known as IL-6, are high in patients with DMD.


Duchenne's muscular dystrophy is the most common of a group of genetic diseases when muscles become progressively weakened and wasted. It is caused by an abnormality of the dystrophin gene that is involved in the function of muscle cells. One in around 3,500 boys is affected. Little boys under the age of three will find walking, running and jumping difficult, and by the age of 11 they are unable to walk.


"These children have very fragile bones that fracture easily," said Dr Rufo at the European Symposium on Calcified Tissues in Vienna today (25 May). "We thought that this was due to mechanical failure - the load on the bones - but felt sure that other factors were involved," she explained.


The abnormal dystrophin gene causes muscle fibres to degenerate and become inflamed. As well as muscle damage, patients have osteoporosis and therefore a greater risk of fractures.


Dr Rufo's team at the University of L'Aquila found that children with DMD have increased levels of IL-6, a molecule that is also know to reduce bone formation and increase bone removal. In laboratory studies, the bone mass was reduced in dystrophin-deficient mice shown by the reduced bone forming cells (osteoblasts) and increased bone removal cells (osteoclast). When healthy osteoblasts were treated with sera collected from DMD patients they failed to mineralise the bone matrix and their IL-6 levels were increased. More than 100 other genes linked to osteoblast-osteoclast 'cross-talk' were also affected.


Their work is significant because glucocorticoids may be given to patients to help improve muscle strength and function for a short period of time. "Glucocorticoids are good for muscles in DMD but not so good for bones," said Dr Rufo. "Now we have found that osteoporosis in DMD patients could partly be explained by IL-6, we can try and find new ways to tackle inflammation," she concluded.


Source: Snell Communications Ltd

Medical Spending For U.S. Residents With Back, Neck Problems Increased By 65% From 1997 To 2005, Study Finds

U.S. spending on diagnosis and treatment of spinal problems increased from 1997 to 2005, but even so, the percentage of patients who reported physical, professional and social limitations as a result of such conditions also increased during the same period, according to a study published on Wednesday in the Journal of the American Medical Association, Reuters/Los Angeles Times reports (Reuters/Los Angeles Times, 2/13).

For the study, led by Brook Martin of the Department of Orthopedics and Sports Medicine at the University of Washington, researchers analyzed data from household surveys conducted by the Agency for Healthcare Research and Quality annually from 1997 to 2005. The surveys each year included responses from about 23,000 U.S. residents. Researchers used the surveys, which included pharmacy and medical record data, to estimate spending on diagnosis and treatment of spinal problems (Parker-Pope, New York Times, 2/13).

According to the study, although spending on diagnosis and treatment of spinal problems increased by an estimated 65% from 1997 to 2005, the percentage of patients who continued to report physical, professional and social limitations as a result of such conditions also increased from an estimated 20.4% to 24.7% during the same period (Reuters/Los Angeles Times, 2/13).

The study found that outpatient spending on spinal problems increased by an estimated 74%, to about $31 million, from 1997 to 2005 and that spending on emergency care for such conditions increased by an estimated 46%, to about $2.6 billion, during the same period. In addition, the study found that spending on surgeries and other inpatient hospital care for spinal problems increased by an estimated 25%, to about $24 billion, from 1997 to 2005.

Comments
Martin said, "We're putting a lot of money into this problem, and it's a big investment in health care expenditures, but we're not seeing health status commensurate with those investments" (New York Times, 2/13). Martin added, "Nobody has a good answer for how much is too much" treatment for spinal problems (Rubin, USA Today, 2/13).

Richard Deyo, a physician at the Oregon Health and Science University and a co-author of the study, said, "I do worry there is a combination of side effects and unnecessary treatments, and labeling people as being fragile when they're really not." He added, "The combination of those kinds of things may actually be in some cases doing more harm than good" (New York Times, 2/13).

However, Stephen Ondra, an associate professor of neurological surgery at Northwestern University, said that, because the study involved an analysis of surveys, the results are "not a valid tool to assess treatment or outcome" (Lopatto, Bloomberg/Philadelphia Inquirer, 2/13).


An abstract of the study is available online.


Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

New Procedure Straightens Bunions Without Cutting Bone

A less invasive, surgical treatment for bunions known as the Mini TightRope procedure is being used at Rush University Medical Center to correct bunions, or hallux valgus, a common, often painful deformity in which the big toe is angled in toward the smaller toes.


The new procedure, developed by orthopedic surgeon Dr. George Holmes, head of the foot and ankle program at Rush and assistant professor of orthopedic surgery at Rush University, uses a special suture material called fiberwire to bind together the first and second metatarsals, the bones in the foot in the big toe and second toe. This pulls the first metatarsal into proper alignment.


Traditionally, people suffering from pain bunions require an osteotomy bunionectomy in the first metatarsal to correct the deformity. This requires a surgeon to break the bone or cut into the bone and reposition the first metatarsal, which can lead to a long recovery period of six-to-eight weeks, during which patients cannot bear any weight on the foot and must use crutches.


"Why should we break the bone in the foot if we do not need to do so to correct the angular deformity," said Holmes. "This is the genesis of the new technique."


"This new procedure decreases the degree of postoperative pain and greatly reduces the potential of postoperative complications," said Holmes. "It also decreases the recovery time, causes less scarring, and patients are able to go home the same day."


During the Mini TightRope procedure, tiny holes about one millimeter in diameter are drilled through the first and second metatarsal bones in the foot. Then, two sets of fiberwire suture, made of a strong, hair-thin mesh and wire-like material, are threaded through the openings, anchored on either side of the metatarsals, and after the sutures are in place, they are tightened to correct the position and alignment of the big toe.


Afterwards, patients wear a postoperative shoe or short walking boot. Stitches are generally removed in two-to-three weeks. Most patients are pain-free within two-to-three weeks.


Bunions are a common type of deformity that develops when weakened muscles and ligaments holding the first metatarsal bone in place shift away from the other toes. At the same time, the big toe slips to the inside and causes the angular deformity.


The joint at the base of the big toe pushes out and causes the formation of a bump along the inner edge of the foot. This bump can become red and swollen and rub against the side of a shoe, which can cause considerable pain when standing, walking or running. In some cases, the bump can be so large and painful that a patient is unable to wear shoes.


An estimated 200,000 bunion correction surgeries are performed in the U.S. each year. About 10 to 30 percent of patients, who have bunion surgery, experience significant complications. One-third of women in the U.S. have bunions. The most common cause of bunions is wearing tight, poorly fitting or high-heeled shoes.


About Rush University Medical Center


Rush University Medical Center is an academic medical center that encompasses the more than 600 staffed-bed hospital (including Rush Children's Hospital), the Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, and one of the nation's top-ranked nursing colleges. Rush University also offers graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness, neurological disorders and diseases associated with aging.


Source: Rush University Medical Center

Cancer Treatment May Result In Bone Loss - New Cross Canada Study

A new cross-Canada study has found that breast and prostate cancer treatment can foster bone loss. In the online edition of the American Society of Clinical Oncology, the scientists explain how loss of bone mass might affect 46,000 people diagnosed with breast and prostate cancer each year* and place them at increased risk for osteoporosis and fractures.


"Our study also looked at possible medications that can reverse or halt bone loss," says Dr. Fred Saad, lead author and director of urologic oncology at the UniversitГ© de MontrГ©al's Faculty of Medicine and the Centre Hospitalier de l'UniversitГ© de MontrГ©al (CHUM), who completed the exhaustive study with colleagues from McMaster University, the UniversitГ© Laval, the University of Toronto and the University of British Columbia.



"Bone is a dynamic tissue which undergoes a cyclic process of breaking down and rebuilding," adds Dr. Saad. "Medications called bisphosphonates help with the rebuilding process and have been successfully used to combat osteoporosis, which is good news for cancer patients."


Evaluating the studies


Dr. Saad and colleagues evaluated data from more than 3,500 breast and prostate cancer studies. They concluded that breast cancer patients treated with aromatase inhibitors were more likely to have bone loss and fractures compared to patients who didn't receive the therapy. Similarly, men who received androgen deprivation therapy to treat their prostate cancer had an increased risk of bone disorders. Although the numbers vary from one study to the next (from five to 45 percent), an elevated risk is consistently observed.


"Awareness of the incidence of cancer-associated bone loss raises issues for clinicians who should identify those patients who are most at risk for fractures and prescribe treatment strategies," says Dr. Saad. "This information is not only a concern for the specialists, but also for the general practitioners who frequently encounter these patients."


Bisphosphonate treatment reduces bone loss


Dr. Saad's group also evaluated data that included bisphosphonate treatment for cancer patients receiving chemotherapy. Prostate cancer patients who received bisphosphonate treatment and androgen deprivation therapy did show an increase in bone loss. In the same vane, there was a protective effect on bone loss for breast cancer patients who were treated with bisphosphonates.


"It is clear that the use of bisphosphonates attenuates bone loss," concludes Dr. Saad. "However, the optimal dosing and long-term impact is unclear and needs to be determined. Other measures to combat the bone loss, such as exercise, vitamin D intake, avoidance of cigarettes, may also be beneficial


*(Re: Canadian Cancer Society)


About the study


The article "Cancer Treatment - Induced Bone Loss in Breast and Prostate Cancer," published in the American Society of Clinical Oncology, was authored by Fred Saad from the UniversitГ© de MontrГ©al and the Centre hospitalier de l'UniversitГ© de MontrГ©al; Jonathan D. Adachi of McMaster University; Jacques P. Brown of the UniversitГ© Laval; Leah A. Canning and Karen A. Gelmon of the University of British Columbia; Robert G. Josse and Kathleen I. Pritchard of the University of Toronto.


Partners in research


This study was funded through grants from Sanofi-Aventis Canada Inc.


On the Web


About the Journal of Clinical oncology

About the Centre Hospitalier de l'UniversitГ© de MontrГ©al

About the McMaster University

About the UniversitГ© Laval

About the University of Toronto

About the University of British Columbia

Potential Treatment For Cancer That Has Metastasized To Soft Tissues And Bones; Option For Those Who Are Not Candidates For Surgery

Cryotherapy, an interventional radiology treatment to freeze cancer tumors, may become the treatment of the future for cancer that has metastasized in soft tissues (such as ovarian cancer) and in bone tumors. Such patients are often not candidates for surgery and would benefit from minimally invasive treatment, said researchers at the Society of Interventional Radiology's 35th Annual Scientific Meeting in Tampa, Fla.



"Improved treatment options are needed for individuals affected by metastases in bone and soft tissues since patients with multifocal metastatic disease are often not candidates for surgery," said Peter J. Littrup, M.D., an interventional radiologist and director of imaging research and image-guided therapy for the Barbara Ann Karmanos Cancer Institute in Detroit, Mich. "Percutaneous soft tissue cryotherapy is a well-tolerated treatment option, especially for patients with anesthesia risks, painful lesions or those seeking local control during chemotherapy. Tumor size and/or location do not preclude thorough treatment or pose greater risk with appropriate precautions," added Littrup, who is also a professor of radiology, urology and radiation oncology at Wayne State University in Detroit. In the 97-patient study, researchers used sufficient deadly temperatures to effectively kill tumor cells, resulting in an average of 77 percent tumor shrinkage in patients after 24 months. "Because of the variable placement of tumors within these soft tissue and bone locations, this study shows the versatility of this treatment option when using proper techniques to safeguard nearby structures. Aside from the successful tumor control, what makes this technique even more preferable is the excellent tumor shrinkage since the underlying fibrous or collagenous structures are preserved. The body can then better heal at the ablation (removal) site with minimal additional scar tissue formation," said Littrup.



Last year, it was estimated that 1.5 million new cases of cancer were diagnosed, and up to 85 percent of patients who have breast, prostate or lung cancer have bone metastases at the time of death. Additionally, 5 percent of all cancers result in skin cancer as well. Based on these numbers, conservative estimates determine that up to 500,000 of these newly diagnosed cancer patients alone will suffer from metastatic disease in bone and soft tissue areas. Cryotherapy is a good option for a large - but perhaps under-recognized - problem that could deliver a quantum impact. Namely, the original cancer tumor site (or even a few unresponsive tumors sites) can still cause cancer management problems even after a generally good response to chemotherapy and/or radiation therapy, said Littrup. "Metastasized tumors can occur nearly anywhere in the body and frequently cannot receive additional radiation therapy or would be difficult or very morbid to be controlled with surgery," said Littrup. "Cryotherapy was able to preserve quality of life by providing good local treatment with minimal side effects, especially with advanced stages of cancer where any additional treatment is unlikely to provide a systemic cure," he added. However, cryotherapy is not a first-line therapy for tumor treatment. Despite "superb" cryotherapy outcomes for many tumor types and locations, medical insurance may not cover the treatment, said Littrup.
















Historically, cyoablation has been performed on the prostate and liver, but this technique has been recently found effective in other tumors including the breast, kidney and lung. "We simply translated this concept to retroperitoneal, intraperitoneal, superficial and bone locations in order to generate successful use of cryotherapy in different patient groups," said Littrup. The major benefits of cryotherapy are its superb visualization of the ice treatment zone during the procedure, its low pain profile in an outpatient setting and its excellent healing with minimal scar, said Littrup. In this study's cryotherapy treatment, researchers used several needle-like cryoprobes that were inserted through the skin to deliver extremely cold gas directly to a tumor to freeze it. This technique has been used for many years by surgeons in the operating room; however, in the last few years, the needles have become small enough to be used by interventional radiologists through a small nick in the skin, without the need for an operation. The "ice ball" that is created around the needle grows in size and destroys the frozen tumor cells. Surgeons and radiation oncologists have long tried to provide at least a 1-centimer margin of treatment with cancer tumors, and it was important to assure a similar "surgical margin" of lethal temperatures beyond all tumor margins by cryotherapy in this study, said Littrup.



"One of our first soft tissue cryotherapy patients with recurrent ovarian cancer encouraged us to really begin this study. She appropriately noted that with recurrent cancer, second- and third-line chemotherapy drugs can run up to $20,000,000 per month and that additional debulking surgery needed at least an additional month of recovery," said Littrup. This patient has now undergone seven cryoablation procedures over the last five years in combination with only a few additional cycles of chemotherapy when more than one to two recurrences were noted, he said. "She called cryotherapy a major 'holiday' from chemotherapy and has been one of our big advocates, referring many other ovarian cancer patients with isolated recurrences," said Littrup.



In the study, 157 computed tomography/CT- and/or ultrasound/US-guided percutaneous cryotherapy procedures were performed (retroperitoneal, 30; intraperitoneal, 51; superficial, 47; and bone, 29) in 97 patients. Protection of adjacent crucial tissues (for example, skin, bowel) from cytotoxic temperatures was achieved by thermocouple monitoring, saline injection and/or direct skin warming. Patients were followed by CT or magnetic resonance imaging (MRI). The cryotherapy zone was well-defined by CT as a hypodense ice ball with an average ablation diameter of 5.4 centimeters; average tumor diameter was 3.5 centimeters.



Interventional radiologists are leaders in percutaneous cryotherapy because it requires interventional skills and a thorough understanding of cross-sectional imaging (US, CT, MRI) and IRs are the only physicians who have this rigorously trained skill set combination, said Littrup. Continued study is needed to determine the optimum probe number, spacing and freeze times needed to produce thorough ice coverage of all soft tissue tumors, he said. "With recent developments of powerful new cryotechnology, multiple directions for soft tissue cryotherapy can be pursued, including translating the current, somewhat challenging, procedure done with ultrasound and/or CT guidance to a more consistent and reproducible MR-guided approach," said Littrup. Cryotechnology promises to be more MR-compatible and would also allow accurate targeting of more difficult-to-see tumors. More importantly, larger studies in multiple centers needs to be done, following these basic cryobiology principles of sufficient lethal temperatures generated by multiple cryoprobes spaced evenly throughout a cancer region, he added.



Abstract 155: "Soft Tissue Cryotherapy: Initial Experience and Intermediate Follow-up in Retroperitoneal, Intraperitoneal, Superficial and Bone Locations," H.J. Bang, Wayne State University, Detroit, Mich.; P.J. Littrup and H. Aoun, Karmanos Cancer Institute, Detroit, Mich.; M. D'Agostini, Michigan State University, Lansing, Mich.; and D.J. Goodrich, University of California, Los Angeles, Calif., SIR 35th Annual Scientific Meeting March 13, 2010, Tampa, Fla.



Source:

Maryann Verrillo

Society of Interventional Radiology

New Alternatives For Bone Imaging Could Be On The Horizon

On June 4, the U.S. Centers for Medicare & Medicaid Services (CMS) announced that it is considering a pathway for coverage of Sodium Fluoride (NaF-18) for PET bone imaging as an alternative to Technetium-99m imaging. Currently, Tc-99m bone imaging is one of the more commonly performed procedures using this radioisotope. Technetium-99m is in scant supply because of ongoing production outages, resulting in serious delays in patient imaging studies for many medical problems, including oncologic, cardiac and neurologic conditions.



Because of the severity of the radioisotope supply crisis and the long-term duration of the anticipated outage, CMS has opened the PET National Coverage Determination (NCD) to evaluate the effectiveness of the radiotracer Sodium Fluoride (NaF-18) for PET bone imaging. PET bone imaging is a nuclear medicine procedure that is sensitive for the detection of the spread of many common cancers - such as breast, lung and prostate - to the bone. It also can be used to detect fractures when X rays do not provide a definitive diagnosis, particularly in pediatric patients.



Currently, about 80% of the world's nuclear medicine scans are performed using Technetium-99m. However, the medical community depends on only six nuclear reactors in the world for over 30 million nuclear medicine tests performed annually with this critical isotope. A shutdown last month at one of these reactors in Chalk River, Canada, has already left thousands of hospitals in the U.S. and Canada without access to this medical isotope.



"The medical community is in crisis right now," said Robert W. Atcher, Ph.D., M.B.A., president of SNM and chair of the society's isotope task force. "Physicians can't get access to essential isotopes for common nuclear medicine procedures. As a consequence, patients are being denied tests, or have to be diagnosed with procedures that involve more radiation dose, less accuracy, more cost or more invasive techniques."



While F-18 as fluorodeoxyglucose (FDG) has been approved by the U.S. Food and Drug Administration (FDA), CMS does not currently reimburse for F-18 fluoride PET bone imaging procedures for the many Americans who would be eligible for coverage as Medicare recipients.



"This reopening paves the way for Medicare beneficiaries who need critical tests to get the coverage and support they deserve," added Atcher. "We encourage CMS to consider the most efficient path forward to provide both themselves and the medical field with sufficient information to analyze and open access to patients across the nation."



"This is very good news," said Barry Siegel, M.D., chief of nuclear medicine at the Mallinckrodt Institute of Radiology, St. Louis, Mo., and co-chair of the NOPR working group. "With the potential for a coverage opening, physicians will be able to provide the evidence necessary to build the case that F-18 fluoride is a viable alternative to Tc-99m in this situation - a case the preliminary evidence suggests will be readily made."



SNM is actively working with CMS and members of the imaging community to submit data and ensure that CMS has the necessary information to cover F-18 fluoride for PET bone imaging procedures.



Source:
Amy Shaw


Society of Nuclear Medicine

Hip Fractures Linked To Prolonged Use Of PPI Antacids In The Over 50s

US scientists have discovered that prolonged use of antacids of the Proton Pump Inhibitor (PPI) type, particulary at high doses, is linked to increased
risk of hip fracture in the over 50s.


The research is reported in today's issue of the Journal of the American Medical Association.


The study was led by epidemiologist and biostatistician Dr Yu-Xiao Yang, of the University of Pennsylvania School of Medicine, Philadelphia. The researchers
conducted a nested case-control study using data from the UK's General Practice Research Database (from 1987 to 2003) on patients who were over 50 years
old. The cohort were either users of PPIs or non-users of antacids. They examined a total of 13,556 cases with hip fractures and 135,386 "healthy"
subjects.


The results suggest that compared to those people that did not use antacids, the people who used a PPI for more than 12 months increased the risk of having
a fractured hip by 44 per cent. And this risk was 2.6 times more for those patients on high doses. In other words the increased risk of hip fracture was
significantly linked to both prolonged use and high dosage.


Proton Pump Inhibitors (PPI) are a range of antacid drugs with names ending in "prazole" such as Pantoprazole (e.g. branded as Protonix), Lansoprazole (e.g.
Prevacid), Rabeprazole (e.g. Aciphex), Omeprazole (e.g. Losec). People use PPIs to control stomach acidity, dyspepsia, stomach ulcers, and to treat
gastroesophageal reflux disease (GERD, or acid reflux).



The amount of hydrogen ions, or H+ (also known as "protons") in your stomach content is a measure of its acidity. Too much H+ slows down healing of duodenal ulcers
, and you also suffer uncomfortable pains like heartburn. The "proton pump" is the process where H+ ions are pumped into the stomach through the lining or
"lumen" from the parietal cells that lie just behind it.


The proton pump inhibitor (PPI) when swallowed is chemically inactive, but once it travels through the
stomach wall into the parietal cells it becomes active. In the active form it reacts with the proton pump thereby reducing its ability to generate H+ ions
for release into the stomach.















The chemical action of the proton pump inhibitor is not reversible, and the effect can last several days. Prolonged use is risky, since it means that the
amount of H+ released into the stomach can drop below a safe level which results in the condition known as hypochlorhydria which is also associated with poor
absortion of calcium and difficulties regulating pathogens such as those that cause pneumonia.


It is this link between PPIs and reduced calcium absorption that this latest study has explored. The link is not just via the reduced stomach acid route,
but also through another process where PPIs may be interfering with another proton pump that helps with reclamation of calcium in "bone resorption".


Our bones are not "dead" matter but very much alive, undergoing a continual process of formation and resorption - a form of recycling where special cells
called osteoclasts burrow into the bone tissue helping to reclaim precious minerals and compounds like calcium, magnesium, phosphates and collagen which are
released into the bloodstream. A proton pump is involved in this process too.


In children the balance between formation and resorption is in favour of formation, which is why intake of calcium and other minerals essential for healthy
bone tissue is so important at that age. In older people resorption exceeds formation, so extra calcium and other minerals are unlikely to be needed in the
diet, unless of course the resorption process is hampered in some way.


If the resorption process is hampered, in the older person this leads to lack of calcium and other nutrients for bone repair and maintenance, which means
higher risk of fracture, for example in the hips.





"Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture."

Yu-Xiao Yang, MD, MSCE; James D. Lewis, MD, MSCE; Solomon Epstein, MD; David C. Metz, MD.

JAMA. 2006;296:2947-2953.



Click here for Abstract.


Written by: Catharine Paddock





View drug information on Aciphex; PREVACID; Protonix.

Cedars-Sinai Foot And Ankle Surgeon Named Head Of California Orthopaedic Association

Glenn Pfeffer, M.D., director of the Foot and Ankle Center at Cedars-Sinai Medical Center, has been elected president of the California Orthopaedic Association, an organization representing more than 2,000 orthopaedists in California. Pfeffer, who is also co-director of the Cedars-Sinai/USC Dance Medicine Center, will serve as the organization's leader for a one-year term beginning in June 2010.


As president, Pfeffer will help steer the medical, legislative and professional agenda for the organization during a time of transition in the nation's healthcare system.


Pfeffer, whose primary clinical and research interests involve reconstruction and sports injuries of the foot and ankle, is past president of the American Orthopaedic Foot and Ankle Society and the American Association of Foot and Ankle surgeons. He is a past member of the board of the American Academy of Orthopaedic Surgeons and chairman of their Council of Musculospecialty Specialty Societies. He is a board-certified orthopaedic surgeon, a diplomate of the American Board of Orthopaedic Surgery and a fellow of the American College of Surgeons.


Pfeffer is also the author of dozens of articles published in peer-reviewed scientific publications and has edited seven textbooks on the foot and ankle. He is on the editorial board of the American Journal of Orthopaedics.


"Glenn Pfeffer is a nationally recognized and respected orthopaedic surgeon," said Diane Przepiorski, executive director of the California Orthopaedic Association. "His dynamic leadership abilities will serve him well in his new role of president of our organization."


Source
Cedars-Sinai Medical Center

Discovery Of New Mode Of Gene Regulation In Mammals

Researchers at the University of California, Santa Cruz, have discovered a type of gene regulation never before observed in mammals--a "ribozyme" that controls the activity of an important family of genes in several different species.



The findings, published in the journal Nature, describe a new and surprising role for the so-called hammerhead ribozyme, an unusual molecule previously associated with obscure virus-like plant pathogens called viroids. The UCSC researchers found the ribozyme embedded within certain genes in mice, rats, horses, platypuses, and several other mammals. The genes are involved in the immune response and bone metabolism.



"The unique thing about these ribozymes is that they control the expression of the genes they're embedded in," said Monika Martick, a UCSC postdoctoral researcher and first author of the Nature paper.



A ribozyme, or "RNA enzyme," is an RNA molecule that can catalyze a chemical reaction. RNA is better known for its ability to encode genetic information, while most biological reactions are carried out by enzymes made of protein. Scientists are discovering, however, that RNA is a remarkably versatile type of molecule.



"RNA can function in the biology of organisms in more ways than we tend to give it credit for," said coauthor Lucas Horan, a graduate student in molecular, cell, and developmental biology at UCSC.



When a gene is activated or "expressed," its DNA sequence on the chromosome is transcribed into an RNA molecule called a messenger RNA. The messenger RNA sequence is then translated into the amino acid sequence of a protein molecule, and the protein then carries out the gene's function in the cell.



In the genes studied by Martick and Horan, the messenger RNA contains sequences that assemble to form an active hammerhead ribozyme. The hammerhead ribozyme is a self-cleaving molecule that essentially cuts itself in two. This self-cleaving action in the messenger RNAs effectively turns off the genes by preventing protein translation. Presumably, another mechanism exists to turn on the genes by stopping the self-cleaving action of the ribozyme.



"We don't know what the switch is to shut off the action of the ribozyme, but we assume there is one," Martick said.



She and her coauthors are all affiliated with UCSC's Center for the Molecular Biology of RNA, directed by Harry Noller, Sinsheimer professor of molecular biology. As a graduate student working with William Scott, professor of chemistry and biochemistry, Martick had determined the three-dimensional structure of the hammerhead ribozyme (see earlier press release at press.ucsc/text.asp?pid=907).



Scott and his research group have been working on the structure and mechanism of the hammerhead ribozyme since before his arrival at UCSC in 1998. "This is the most remarkable and unexpected discovery I have seen during that time," he said.



For the new study, Martick teamed up with Horan, a graduate student in Noller's lab. Scott and Noller are both coauthors of the Nature paper.
















"Monika clued me in that she had found something interesting, and we decided to try to figure out what was going on," Horan said. "She had just finished her Ph.D., and I was working on something else, but we got some preliminary data and it turned out to be a very fruitful collaboration; it's the kind of interaction that the RNA Center is meant to stimulate."



Martick performed the initial searches that turned up the hammerhead ribozyme sequences in the mouse and rat genomes. Then she and Horan did more exhaustive searches of the genomic sequences of other organisms, using the UCSC Genome Browser and other databases. They found the ribozyme in related genes in the mouse, rat, horse, and platypus, and in unknown genes in five other mammals.



"We used to think the hammerhead ribozyme was restricted to obscure plant viruses, but it now looks like it is featured much more prominently in mammalian biological systems," Scott said.



Laboratory experiments showed that the messenger RNAs containing the embedded sequences form an active ribozyme and that the ribozyme decreases gene activity in mammalian cells.



"This mode of gene regulation hadn't been seen before in mammals," Horan said. "Because it occurs in such a wide variety of organisms, including the platypus, it must have been around since the early mammalian ancestors."



The researchers did not find the ribozyme sequence in the corresponding human genes, however, suggesting that a different mechanism regulates those genes in humans.



"These genes are involved in the immune response and in bone metabolism, so they are being intensively studied on two fronts," Martick said. "It's important to understand how that system is regulated and if the rodent system is regulated differently from the human system."







Source: Tim Stephens


University of California - Santa Cruz

Five Signs Your Child May Have A Foot Problem

Foot and ankle problems in children often go unnoticed. Signs and symptoms can be subtle, and sometimes children can't explain what's wrong. But it's important to protect growing feet and have problems checked out early.


The American College of Foot and Ankle Surgeons offers five warning signs parents should watch for.


1. Your Kids Can't Keep Up with Their Peers


If children lag behind in sports or backyard play, it may be because their feet or legs are tired. Fatigue is common when children have flat feet. The muscles in the feet and legs tire easily because the feet are not functioning as well as they should.


2. Children Voluntarily Withdraw from Activities they Usually Enjoy


If they are reluctant to participate, it may be due to heel pain a problem often seen in children between the ages of 8 and 14. Repetitive stress from sports may cause muscle strain and inflammation of the growth plate, a weak area at the back of a child's heel.


3. They Don't Want to Show You Their Feet


Children may feel pain or notice a change in the appearance of their feet or nails but don't tell their parents because they fear a trip to the doctor's office. Surgeons encourage parents to make a habit of inspecting their child's feet starting at a young age. Look for any changes such as calluses, growths, skin discoloration, or redness and swelling around the toenails.


4. Your Child Often Trips and Falls


Repeated clumsiness may be a sign of in-toeing, balance problems or neuromuscular conditions.


5. The Child Complains of Pain


It is never normal for a child to have foot pain. Injuries may seem minor, but if pain or swelling last more than a few days, have your child's foot examined.


A child with any of these signs or symptoms should be promptly examined by a foot and ankle surgeon for proper diagnosis and treatment.


Source: American College of Foot and Ankle Surgeons

TAU Develops Superior Method For Coating Orthopaedic And Dental Implants

Tel Aviv University researcher Prof. Noam Eliaz of the TAU School of Mechanical Engineering has developed an electrochemical process for coating metal implants which vastly improves their functionality, longevity and integration into the body.



The new process could vastly improve the lives of people who have undergone complicated total joint replacement surgeries so they can better walk, run and ultimately avoid rejection of the implant by their bodies.



"The surface chemistry, structure and morphology of our new coatings resemble biological material," explains Prof. Eliaz. "We've been able to enhance the integration of the coating with the mineralized tissue of the body, allowing more peoples' bodies to accept implants." His new coating resulted in a 33% decrease in the level of materials failure, or delamination, in these implants.



Prof. Eliaz presented his findings to the 215th meeting of the Electrochemical Society in San Francisco in May 2009. In addition, a new 12-week implantation study, recently published in the journal Acta Biomaterialia, favorably compared the performance of the Tel Aviv University coatings to those of current commercial coatings.



Giving your joints an electrochemical bath



Today's surgeons can reconstruct joints in the human body using metal structures implanted to take the place of the natural joint. In order to better integrate the new addition to the adjacent bone, implants are often coated with synthetic hydroxyapatite, which is similar to the main inorganic constituent of enamel, dentin and vertebrate bone. The properties of this coating are crucial to the function and life of the implant in the body.



Prof. Eliaz's advance is in the application technique of the coatings rather than the elements used in the coatings themselves. Instead of the traditional plasma-spraying technique, he and his team from the Tel Aviv University Materials and Nanotechnologies Program have developed a way to electrochemically deposit synthetic hydroxyapatite. In place of plasma-spraying the coating onto the metal, the metal implant is placed into a bath of electrolyte solution and an electric current is applied.



According to Prof. Eliaz, a good coating is crucial to the stable fixation of the implant in the surrounding bone. Since human bones naturally contain apatite, covering the implant with a synthetic version allows the body to register the implant as similar to a real bone. This ensures integration and fixation of the implant, and also prevents poisonous materials from leaking from the metal of the implant into the blood stream.



Could spur new bone growth



Prof. Eliaz has discovered that his method of coating circumvents the disadvantages of plasma-spraying. The electrochemical process allows synthetic hydroxyapatite to more closely mimic the real material. Examined under a microscope, it is virtually indistinguishable from the body's own material - which helps the body accept a new implant.



The next-generation coating will include nano-particles to reinforce the coating. It will also have the potential to incorporate biological material or drugs during the process itself.



"We can incorporate biological materials" because the electrochemical process works at lower temperatures, says Prof. Eliaz. "The reinforcement of nanoparticles will improve the mechanical properties and may also improve the biological response. Drug incorporation may reduce the risk of post-surgery infection and even catalyze the growth of the bone."



Source:
George Hunka


American Friends of Tel Aviv University

Gum Disease In Postmenopausal Women Linked To Oral Bone Loss

A study conducted in a large sample of postmenopausal women by University at Buffalo epidemiologists has provided new information on the prevalence of certain gum-disease-causing oral bacteria in this population and the association of the bacteria with oral bone loss.



Results showed that women infected with four bacteria known to cause periodontal disease were more likely to have more severe oral bone loss than those without these oral pathogens.



Two widely recognized periodontal pathogens, called P. gingivalis and T. forsythensis, were found to infect 15.1 percent and 37.9 percent of the women, respectively. Two additional oral bacteria suspected to be pathogenic, P. intermedia and C. rectus, were found in 43.4 percent and 17.4 percent of women.



"This is one of the first studies in community-dwelling postmenopausal women that assessed bacteria presence and associated it with oral bone loss, while controlling for other factors, such as age, smoking status and income," said Jean Wactawski-Wende, Ph.D., associate professor of social and preventive medicine, UB School of Public Health and Health Professions, and senior author on the study



Results appear in the June 2007 issue of the Journal of Periodontology.



The study involved 1,256 postmenopausal women who were part of a larger population-based investigation of risk factors for osteoporosis and oral bone loss in postmenopausal women, which is an offshoot of the observational portion of the national Women's Health Initiative (WHI).



Participants in this study completed questionnaires, had physical measurements taken, had bone-density testing and an oral health examination. The oral health examination had several components, including microbiological sampling of subgingival plaque and oral X-rays.



Investigators used a measure called alveolar crestal height to determine the amount of oral bone loss. Alveolar bone surrounds the teeth and holds them in place in the upper and lower jaw. The lower the crest, or top of the bone, the more bone has been lost. Loss of alveolar crest bone eventually can lead to tooth loss.



The association between bacterial infection and oral bone loss turned out to be strongest in overweight women, compared to normal weight or obese women.



"We expected to see an increased risk for oral bone loss with increasing body mass index (BMI, a factor representing the relationship of weight to height)," commented Renee Brennan, Ph.D., research assistant professor of social and preventive medicine and first author on the study.



"However, the greatest risk was seen in overweight women. This was supported by a three-fold increase in these women. Other factors that we could not assess may be at play in the obese women. We need to explore further the impact of weight and BMI on the associations of oral bacteria and oral bone loss."



Blood levels of inflammation markers, which would provide a clear picture of overall risk weren't available at the time, but the researchers now are planning to investigate this association.



In addition to substantiating the relationship between certain known and suspected oral pathogens and oral bone loss, results confirmed that the three control bacteria included in the study, which have not been associated with periodontal disease, also were not associated with oral bone loss.



On the contrary, the two control bacteria -- S. sanguis and Capnocytophaga sp. -- were associated with healthier oral bone.



Brennan said the findings will help develop a more complete understanding of the mechanisms involved in periodontal disease.







Additional authors on the study, all from UB, are Robert J. Genco, D.D.S., Ph.D., SUNY Distinguished Professor and UB professor of oral biology, School of Dental Medicine; Gregory E. Wilding, Ph.D., assistant professor of biostatistics; Kathleen M. Hovey, statistician; and Maurizio Trevisan, M.D., dean of the School of Public Health and Health Professions and professor of social and preventive medicine.



The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The School of Public Health and Health Professions and the School of Dental Medicine are two of five schools that constitute UB's Academic Health Center.



Contact: Lois Baker


University at Buffalo

Breakthroughs In Treatment Of Spine And Back Conditions

Approximately 21 million visits were made to physicians' offices due to back problems in 2006. While countless adults experience back pain and stiffness, many suffer from serious spine and back conditions - including injury, herniated discs and the deterioration of the vertebrae. Three new studies presented at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) detail advances in back care and treatment options for specific back and spine conditions. Each of the following three studies consider and report on the patients' best outcomes and options:
Does the duration of symptoms affect outcomes in the treatment of lumbar disc herniation?


Treatment of Lumbar Spinal Stenosis: Who Decides to Have Surgery?


Balloon Kyphoplasty vs Non-surgical Care: 2 Year Outcome of a Randomized Controlled Trial

Slipped Disc: When to Seek Treatment?



Lumbar disc herniation, or a slipped disc, mainly affects adults aged 30 to 40 years and is commonly caused by degenerative changes in the spine. Typically, these changes produce symptoms gradually, beginning with pain centered in the lower back. With progression of the condition, patients may suffer from extreme back pain and that also may spread into the buttocks and down the legs.



A new study just released analyzed the effect of symptom duration when treating herniated discs in the lower back. A comparison was made between 927 patients who had intervertebral lumbar disc herniation symptoms for less than six months and 265 patients who had symptoms longer than six months. Patients with symptoms lasting longer than six months had worse outcomes after both operative and non-operative treatment than patients with shorter symptom duration.



"The bottom line is patients who seek treatment, whether it is surgical or non-surgical, during the first six months of symptoms will respond better to treatment," said Jeffrey A. Rihn, MD, study co-investigator and assistant professor, Department of Orthopaedic Surgery, Thomas Jefferson University and The Rothman Institute. "We also learned that surgery offers advantages over non-surgical treatment regardless of the duration of symptoms."



Spine Injury in Seniors: Is Surgery For You?



Lumbar spinal stenosis is the leading cause of spine surgery in patients over age 65. Spinal degeneration narrows the spinal canal and compresses the spinal cord and nerves. Previous studies have demonstrated the benefit of surgery over non-surgical management of this condition, however, in these studies it was unclear what were the indications for surgery and largely unknown which patients select surgery.



The study unveiled today looked at 241 patients who underwent surgery and 115 who had non-operative care. Researchers found that patients who chose surgery tended to be:
Younger;















With more pain and more disability; and


Felt their symptoms were progressing.

"These results help complete the evaluation and treatment algorithm for patients with spinal stenosis. The findings will enhance the shared decision-making process by aiding physicians in counseling patients to help them choose the right treatment option," explained Mark F. Kurd, MD, lead author of the study and orthopaedic surgery resident, Thomas Jefferson University and The Rothman Institute.



Vertebral Fractures: Surgical or Non-Surgical Care?



Vertebral compression fractures are one of the most frequent consequences of osteoporosis. They cause pain, disability and diminished quality of life. Current non-surgical treatment options involve pain medication, bed rest, physiotherapy and back bracing. However these options do not address the resulting vertebrae breakdown, height loss and other resulting problems.



Balloon kyphoplasty is a minimally invasive procedure for acute vertebral fractures that reduces and corrects the vertebral deformity by inserting expandable balloon tamps and then filling it with bone cement. In 2007, 46,000 inpatient kyphoplasty procedures were performed in the United States, according to the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project coordinated by the Agency for Healthcare Research & Quality.



Results were presented from a study of 149 patients treated with balloon kyphoplasty and 151 patients treated with non-surgical treatment. Measurements for quality of life, back pain and function, and days of disability were assessed through 24 months of follow-up. Compared to non-surgical care, balloon kyphoplasty:
Improved quality of life;


Reduced back pain and disability; and


Did not increase adverse events including the risk of vertebral fracture over two years.

"I have been using balloon kyphoplasty to treat patients with painful vertebral compression fractures for years so the immediate and sustained pain relief we saw in the study did not surprise me," concluded Jan Van Meirhaeghe, MD, study co-author and orthopaedic surgeon, Department of Orthopaedic Surgery, St-Jans Hospital, Brugge, Belgium and Gent University Hospital, Gent, Belgium. "But until now these decreased pain levels and significant quality of life improvement, as compared to non-surgical treatment, had not been demonstrated in a clinical trial."



Disclosures: Dr. Rihn, Dr. Kurd and their co-authors received no compensation for their studies.


Dr. Van Meirhaeghe or a member of his immediate family received something of value from or owns stock (or stock options) from Medtronic, a commercial company related to the research indicated in this abstract.



Source:

Lauren L. Pearson

American Academy of Orthopaedic Surgeons

Potential Therapy Discovered For Hypophosphatasia, A Congenital Form Of Rickets

Researchers at the Burnham Institute for Medical Research, led by Jose Luis Millan, Ph.D., have demonstrated in mice the first successful use of enzyme replacement therapy to prevent hypophosphatasia (HPP), a primary skeletal disease of genetic origin. This discovery lays the foundation for future clinical trials for HPP patients.



Rickets is a softening of the bones that most commonly results from a lack of vitamin D or calcium and from insufficient exposure to sunlight. Hypophosphatasia is a rare, heritable form of rickets caused by mutations in a gene called TNAP, which is essential for the process that causes minerals such as calcium and phosphorus to be deposited in developing bones and teeth. The physical presentations of this disorder can vary depending on the specific mutation, with more severe symptoms occurring at a younger age of onset. The most severe form of the disease occurs at birth, which can present with absence of bone mineralization in utero, resulting in stillbirth.



Using a mouse model, JosГ© Luis MillГЎn, Ph.D. tested the hypothesis that, when administered from birth, a bone-targeted form of the TNAP gene would ease the skeletal defects of HPP. The MillГЎn laboratory, in collaboration with scientists from Enobia Pharma in Montreal, Canada and from the Shriners Hospitals for Children in St. Louis, Missouri, created a soluble form of human TNAP that had been shown to display a strong attraction to bone tissue. Upon injecting the enzyme into the fat layer under the skin of the mice, the treated mice maintained a healthy rate of growth and apparent well being, as well as normal bone mineral density (BMD) of the skull, femur and spine. In fact, complete preservation of skeletal and dental structures were observed after 15 days, and bone lesions were still not seen after 52 days of treatment.



"While the biochemical mechanism that leads to skeletal and dental defects of HPP is now generally understood," said Dr. MillГЎn, "there is currently no established medical treatment."



Given the success of this therapy in preventing HPP, current efforts in Dr. MillГЎn's laboratory are focused on reversing the bone defects in mice once the disease is quite advanced. Future clinical trials may reveal this as the first promising therapy for patients with this genetic disorder.







This study, published in the Journal of Bone and Mineral Research, was supported by grants from the National Institutes of Health, Enobia Pharma, Inc., and the Shriners Hospitals for Children.



About Burnham Institute for Medical Research



Burnham Institute for Medical Research is dedicated to revealing the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham is one of the fastest growing research institutes in the country with operations in California and Florida. The Institute ranks among the top four institutions nationally for NIH grant funding and among the top 25 organizations worldwide for its research impact. Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, infectious and inflammatory and childhood diseases. The Institute is known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit, public benefit corporation. For more information, please visit burnham/.



Source: Andrea Moser


Burnham Institute

Comprehensive Guidelines For Treating Low-Back Pain Issued By ACP And APS

The American College of Physicians (ACP) and the American Pain Society (APS) have released joint guidelines on diagnosing and treating low back pain.



About one in four Americans reported having low back pain in the past three months and about l7.6 percent of all adults reported at least one episode of severe acute low back pain within the previous year, according to several studies. Other studies show that most people's low back pain will improve within one month, regardless of treatment. Treatments range from doing nothing to spinal surgery.



In 2006, ACP and APS convened a multidisciplinary panel of experts to develop questions and the scope of an evidence report on low back pain, to review its results and come up with recommendations for primary care physicians to diagnose and treat low back pain.



The recommendations, published in the Oct. 2, 2007, issue of Annals of Internal Medicine, include an algorithm to guide clinicians in obtaining and interpreting information during the first patient visit and place patients into one of three general categories:



Nonspecific low back pain (85% of patients fall in this category) -- Back pain potentially associated with spinal conditions, such as spinal stenosis, sciatica, vertebral compression fracture -- Back pain potentially associated with another specific cause, such as cancer.



The recommendations say that clinicians should not routinely order imaging or other diagnostic tests such as X-rays, CAT scans, and MRIs, for patients with nonspecific low back pain. They should reserve these tests for patients who have severe or progressive neurologic deficits or suspected underlying conditions, such as cancer or infection.







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Watch the video documentary that accompanies this article

The joint ACP-APS guidelines are designed for primary care physicians and other clinicians and do not address invasive therapies performed by specialists. The American Pain Society will publish a separate guideline covering invasive procedures for low back pain in 2008.
















"There are many options for evaluation and treatment of low back pain," said Amir Qaseem, MD, PhD, MHA, senior medical associate in the ACP Department of Clinical Programs and Quality of Care, and an author of the guidelines. "We wanted to review all the evidence and develop guidance for clinicians and to give our patients a realistic sense of what they can expect when they visit a clinician for low back pain. It is important to tell patients about their expected course based on evidence-based information and advise them to remain active."



Roger Chou, head of the American Pain Society Clinical Practice Guidelines Program, an author of the guidelines, and the senior author of the two background papers on which the guidelines were based, reviewed evidence for both drug therapies and non-drug therapies for acute and chronic low back pain.



"Almost all medications reviewed had some benefits, but they have risks," Chou said. "Acetaminophen, for example, is very safe but might not be effective. NSAIDS have gastrointestinal and cardiovascular risks. Opioids and muscle relaxers can provide relief for those with severe pain, but their potential benefits and risks should be weighed carefully."



"Patients who prefer not to take medication can benefit from non-drug treatments, such as acupuncture, spinal manipulations and massage therapy. None, however, are proven to be more effective than others to warrant recommendation as first-line therapy."







The following will be published in the October 2, 2007, edition of Annals of Internal Medicine and will be available to the public at annals/:



* "Diagnosis and Treatment of Low Back Pain: A Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society,"



* "Medications for Acute and Chronic Low Back Pain: A Review of the Evidence for an American Pain Society/American College of Physicians Clinical Practice Guideline"



* "Nonpharmacologic Therapies for Acute and Chronic Low Back Pain: A Review of the Evidence for an American Pain Society/American College of Physicians Clinical Practice Guideline"



Annals of Internal Medicine (annals/) is one of the most widely cited peer-reviewed medical journals in the world. The journal has been published for 80 years and accepts only seven percent of the original research studies submitted for publication. Annals of Internal Medicine is published by the American College of Physicians (acponline/), the largest medical specialty organization and the second-largest physician group in the United States.



ACP members include 124,000 internal medicine physicians (internists), related subspecialists, and medical students. Internists specialize in the prevention, detection, and treatment of illness in adults.



Source: Susan Anderson


American College of Physicians

Good Mental Health Prevents Falls: Australian National University Study

Good mental health plays an essential role in keeping elderly people on their feet and preventing major injury through falls, according to research from The Australian National University. The study of 787 adults with an average age of 78 was led by Associate Professor Kaarin Anstey of the ANU Centre for Mental Health Research (CMHR).



Professor Anstey said that falls constitute a major public health problem in later life and are the leading cause unintentional injury and hospitalisation in persons aged 65 and older. With age the danger of falling rises steadily and the risk of death after being hospitalised for a fall is approximately 50 per cent. The cost to the Australian economy from the one in three older adults living at home that have falls each year is over $1 billion annually. Those falls account for 11 per cent of hospital bed days in Australians aged 65 and older.


For the study, the participants were assessed three times over eight years on measures of well being including depressive symptoms, morale and sense of control over their lives.


"After taking into account factors such as age, gender and education as well as whether participants took psychotropic medication, had serious medical conditions or poor balance, we found that lower scores on the well being measures at the first assessment were associated with increased risk of falling over the eight year follow up interval," said Professor Anstey.



"The study also showed that there was an increasing fall rate over time among individuals who reported an increase in depressive symptoms or reduction in morale during the course of the study."


She added that to reduce the danger of damaging falls for Australia's elderly it was essential to promote good mental health.


"The findings of this study clearly show that mental health is strongly linked to physical function in later life and that promoting good mental health as we age has benefits for physical function and mobility. Good mental health is an integral part of healthy ageing," she said.


The study, conducted with Professor Mary Luszcz from Flinders University, used participants from the Australian Longitudinal Study of Ageing.


Souce

Martyn Pearce

Media Officer

Communications and External Liaison Office

Office of the Vice-Chancellor


The Australian National University

A Walking Robot Goes Mountaineering

The human gait is a marvel of coordination. All aspects of movement control - from the angle of the knee joints to the momentum of the hip up to the
balance point of the torso - need to be meticulously adjusted.
In addition, the gait is adaptable to different environments. Walking on ice is different from walking on solid ground, walking uphill is different
from downhill.




In their study, publishing in PLoS Computational Biology July 13, 2007, scientists around Florentin Wörgötter, Bernstein Center for Computational
Neuroscience at the University of Göttingen, have simulated the neuronal principles that form the basis of this adaptivity in a walking robot.
"RunBot", as it is called, lives up to its name - it holds the world record in speed walking for dynamic machines. Now its inventors have expanded
its repertoire. With an infrared eye it can detect a slope on its path and adjust its gait on the spot. Just as a human, it leans forwards slightly
and uses shorter steps. It can learn this behavior using only a few trials.




The robots ability to abruptly switch from one gait to the other is due to the hierarchical organization of the movement control. In this respect, it
resembles that of a human and can hold as a human model. On the lower hierarchical levels, movement is based on reflexes driven by peripheral sensors.
Control circuits ensure that the joints are not overstretched or that the next step is initiated as soon as the foot touches the ground. Only when the
gait needs to be adapted, higher centers of organization step in - a process triggered by the human brain or, in case of the robot, by its infrared
eye leading on to a simpler neural network. Because of the hierarchical organization adjustment of the gait can be achieved by changing only a few
parameters. Other factors will be automatically tuned through the regular circuits.




At its first attempt to climb a slope, RunBot will fall over backwards, as it has not yet learned to react to its visual input with a change in gait.
But just like children, RunBot learns from its failures, leading to a strengthening of the contact between the eye and the sites of movement control.
Only once these connections are established, step length and body posture are controllable by the visually induced signal.
The steeper the slope, the stronger RunBot will adapt its gait.


"Adaptive, fast walking in a biped robot under neuronal control and learning."

Manoonpong P, Geng T, Kulvicius T, Porr B, WoВЁ rgoВЁ tter F (2007)

PLoS Comput Biol 3(7): e134. doi:10.1371/journal.pcbi.0030134

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Laser Melting Bone Replacement

In a medical emergency, a puncture of the cranium is commonly treated with an implant. While replacements made of titanium merely plug holes, a new kind of degradable implant stimulates the body to regenerate itself: It is a custom-fit and disappears to the same extent that the bone regrows.



The body can heal minor bone injuries itself - but with major injuries, it needs help. That's when implants frequently come into use. In contrast to long-term solutions based on titanium, degradable implants are intended to replace the missing pieces of bone only until the fissure closes itself up. That may last months or even years, depending on the size of the defect, the age and health status of the patient. A new implant improves the conditions for the healing process. It emerged from the "Resobone" project of the federal ministry for education and research, and is sized-to-fit for each patient. Unlike the conventional bony substitutes to date, it is not made up as a solid mass, but is porous instead. Precise little channels permeate the implant at intervals of just a few hundred micrometers. "Its precision fit and perfect porous structure, combined with the new biomaterial, promise a total bone reconstruction that was hitherto impossible to achieve," as Dr. Ralf Smeets of the University Medical Center of Aachen summarizes the findings of the first tolerability studies.



The porous canals create a lattice structure which the adjacent bones can grow into. Its basic structure consists of the synthetic polylactide, or PLA for short. The stored granules from tricalcium phosphate (TCP) ensure rigidity and stimulate the bone's natural healing process. As pastes, granulates and semi-finished products, TCP and PLA already have proven to be degradable implants. The body can catabolize both substances as rapidly as the natural bones can regrow. But the material can only be applied in places where it will not be subject to severe stress: Thus, the "Resobone" implants will primarily replace missing facial, maxillary and cranial bones. Currently, they are able to close fissures of up to 25 square centimeters in size. Their unique structure is made possible through a manufacturing process that was developed at the Fraunhofer Institute for Laser Technology ILT in Aachen for the development of industrial prototypes - Selective Laser Melting (SLM): A razor-thin laser beam melts the pulverized material layer-by-layer to structures that may be as delicate as 80 to 100 micrometers.



The patient's computer tomography serves as the template for the precision-fit production of the implants. The work processes - from CT imaging, to construction of the implant, through to its completion - are coordinated in such precise sequences that the replacement for a defective zygomatic bone can be produced in just a few hours, while a five-centimeter large section of cranium can be done overnight. In addition to the obvious benefits, there is a considerable gain in time during surgery: "No custom-fit, degradable implants ever existed before now. During the operation, the surgeon had to cut TCP cubes, or the patient's own previously removed bone material, to size and insert it into the fissure," explains Simon Höges, Project Manager at ILT. In addition, the operations are now fewer in number: Physicians no longer take the bone replacement from the patient's own pelvic bone. Similarly, they can dispense with the countless follow-up operations on children to exchange long-term implants that don't grow as the child matures. "We have achieved our project goal: a closed process chain to produce individual bony implants from degradable materials," explains Höges with satisfaction. Now it is up to the project partners - which also include implant manufacturers - who must turn the results into products.



Source:

Dipl.-Phys. Simon Hoeges


Fraunhofer-Gesellschaft

Research Into Inflammation, Sensory Neurons And Low Back Pain Receives $1.7 Million

The National Institute of Neurological Disorders and Stroke has awarded $1.7 million to University of Cincinnati (UC) anesthesiology researchers to study a condition that costs Americans $50 billion a year - low back pain.



Back pain is the leading cause of disability in Americans younger than 45 years old and is experienced by 50 to 80 percent of adults at some point in their lives. Back pain becomes chronic if it persists for more than three months and the cause can sometimes be difficult to determine.



The UC researchers are focusing their five-year study on inflammation and how its effects on sensory neurons in the low back cause persistent chronic pain.



The team, led by Jun-Ming Zhang, MD, director of UC's Pain Research Center, believes small molecules called chemokines are key factors in the development of pain. Chemokines are a family of small cytokines - chemical "messenger" molecules used by immune and nerve cells to communicate with other cells.



"If we can determine the role these chemokines play in the development of back pain we can hopefully develop better medications to treat the problem," says Zhang.



Zhang says acute (short-term) pain can actually be beneficial. "Acute pain responses to potentially dangerous stimuli - like the neural circuitry that tells you to pull your hand away from a hot stove - are essential for survival," says Zhang.



But when pain becomes chronic, it "serves no useful purpose," he says, and often affects a person's quality of life.



Back pain can be caused by physical trauma such as a sports injury, lifting heavy items or from a car accident, Zhang explains. For others, medical conditions such as a herniated disc cause pain. But many people experience back pain for no apparent reason.



"When a patient goes to the doctor for low back pain, they may undergo an MRI or an X-ray. Sometimes these tests show anatomical reasons for the pain such as a herniated disc. But for some patients, tests don't show any physical evidence for why they are experiencing low back pain," he says.



Zhang adds that the lack of physical evidence can be very frustrating for patients and make it more difficult for doctors to help a patient effectively manage their pain through medication and other treatment therapies.



"That's why we hope to identify specific molecules that contribute to low back pain development. Our goal is to develop a non-opiod analgesic targeting those molecules to alleviate pain," says Zhang.



In previous research, Zhang and his team, including Judith Strong, PhD, co-investigator for the new study, found that pain-sensing neurons can become abnormally sensitive or "fire" spontaneously in the absence of stimuli. This early spontaneous activity plays a key role in setting up the pathological pain state.



"We found that by blocking the early spontaneous activity of an injured nerve we can completely prevent the development of chronic pain. This technique could be extremely useful for combat nerve injuries and amputations that often lead chronic pain," he says.



In the new study, the team will explore how inflammation may contribute to the development of low back pain by intentionally causing this abnormal neuronal firing.







Source: Jamie Kaun


University of Cincinnati

Anesiva Phase 3 Trial Of Adlea Meets Primary Endpoint To Significantly Reduce Pain After Total Knee Replacement Surgery

Anesiva, Inc. (Nasdaq: ANSV) announced top-line results showing that the Phase 3 trial evaluating Adlea(TM), its long-acting, non-opioid analgesic drug candidate, achieved its primary efficacy endpoint of reducing post-surgical pain versus placebo (p=0.03) following total knee arthroplasty (TKA, or total knee replacement surgery) at four to 48 hours after surgery. The trial also met its key secondary endpoint with Adlea demonstrating a highly significant reduction in opioid medication consumption compared to placebo (p=0.005). Adlea is a long-acting, non-opioid drug candidate in development for the management of acute pain following orthopedic surgery.


The Phase 3 TKA trial, known as ACTIVE-2 (Assessment of highly purified Capsaicin To ImproVE pain management after orthopedic surgery), also showed that Adlea's safety profile of adverse events, wound healing, and wound sensory function were similar to placebo over the study duration.


"These compelling results confirm the analgesic contribution of Adlea during the most critical period following total knee arthroplasty with simultaneous opioid sparing effect, all without adding to the systemic side- effects commonly seen with opioids. These results suggest that Adlea has the potential to facilitate early rehabilitation in the knee replacement population," said William Houghton, M.D., Anesiva's senior vice president and chief medical officer.


"The ACTIVE-2 data convincingly validate the value of the Adlea asset and will support our plans to partner or license this product candidate," said Michael L. Kranda, Anesiva's president and chief executive officer.


"Over the past several months, we have revised the company's business model to significantly reduce our burn rate, and will achieve our goal of operating largely as a virtual company by year-end," Mr. Kranda said. "We now have retained a dedicated team ideally suited for Adlea clinical development and partnering within a cost structure that is appropriate for the current environment. With these positive developments, we look forward to rebuilding value for Anesiva through our virtual model, and through active partnering and licensing programs."


ACTIVE-2 Details


This multicenter, double-blind, placebo-controlled trial enrolled 217 patients undergoing total knee arthroplasty. Patients were randomized to receive either a single 60 mL dose of Adlea (0.25 mg/mL drug concentration) or placebo instilled into the surgical site immediately prior to wound closure. The primary efficacy endpoint was the area under the curve of patient pain scores, using a standard 0 to 10 numerical weighting system from four to 48 hours post-surgery. The study also evaluated rescue opioid consumption. Additional patient safety follow-up at two to six weeks after surgery demonstrated an advantage in pain management for Adlea versus placebo, with a similar safety profile.


Adlea Phase 3 Results in Bunionectomy Surgeries















A previous Phase 3 trial of Adlea, ACTIVE-1, in bunionectomy surgeries, demonstrated a highly statistically significant reduction in pain (p=0.004) from 4 to 48 hours post-surgery for Adlea-treated patients versus placebo, although the primary endpoint, pain at 4 to 32 hours post-surgery, narrowly failed to achieve statistical significance (p=0.07). The trial also achieved the key secondary endpoint of reducing opioid use for Adlea versus placebo (p=0.012) over the four to 32 hour period, and Adlea was well-tolerated.


How Adlea May Address the Need for Long-Acting Pain Relief


Adlea is a highly purified form of capsaicin (derived from chili peppers) that acts on TRPV1 receptors, expressed most densely in C-fiber neurons. Importantly, desensitization of the TRPV1 receptors blocks noxious pain with no effect on adaptive pain or position sense. Adlea generally has a short half-life of 1 to 2 hours. It is undetectable in the blood after 24 hours.


Adlea's short duration of systemic exposure (hours) relative to the long duration of analgesia may offer a safe, additive treatment option in the management of orthopedic post-surgical pain. Importantly, Adlea appears to have a safety profile that is largely similar to placebo, in studies performed to date.


About Total Knee Arthroplasty


Total knee replacement (also known as total knee arthroplasty) is generally performed in patients with end-stage osteoarthritis of the knee. These patients have disabling pain which imposes severe limitations on their mobility, and knee replacement is performed with the goal of relieving pain and restoring mobility and knee function. There were an estimated 565,000 total knee replacement procedures performed in the United States in 2006, and the number of replacements will continue to grow as the average age of the U.S. population increases and as these individuals conduct more active lives. The American Academy of Orthopedic Surgeons projects that approximately 3.5 million of these procedures will be done each year by 2030.


About Anesiva


Anesiva, Inc. seeks to be a leader in the development of novel pharmaceutical products for pain management. The company's lead product candidate is Adlea, a novel small molecule formulation of capsaicin that is currently in development for the management of acute pain following orthopedic surgeries. Adlea has been shown in previous clinical trials to provide extended pain relief after only a single administration in multiple indications for site-specific, acute and chronic, moderate-to-severe pain.


Anesiva is based in South San Francisco, CA. For more information, go to anesiva.


Forward Looking Statements


This press release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Words such as "seek," "expect," "estimate," "project," "achieve," "show," "demonstrate," "offer," "plan," "may," "will," "extend," "continue," and similar expressions are intended to identify such forward-looking statements. Forward-looking statements in this press release include matters that involve known and unknown risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to differ materially from results expressed or implied by this press release. Such risk factors include, among others: the nature and extent of additional Adlea clinical trials that may be required by the U.S. Food and Drug Administration prior to Anesiva's submission of an application for approval to market Adlea, and whether any such additional trials will be successful. Actual results may differ materially from those contained in the forward-looking statements in this press release. Additional information concerning these and other risk factors is contained in Anesiva's annual report on Form 10-K for the year ended December 31, 2007, and its most recent filing on Form 10-Q.


Anesiva, Inc.

anesiva