Statin Therapy Associated With Regression Of Coronary Atherosclerosis With Key Lipid Level Changes

An analysis of data from four clinical trials suggests that statin therapy is associated with regression of coronary atherosclerosis when low-density lipoprotein cholesterol (LDL-C or “bad” cholesterol) is substantially reduced and high-density lipoprotein cholesterol (HDL-C or “good” cholesterol) is increased, but it remains to be determined whether this degree of atherosclerosis regression will translate to meaningful reductions in cardiovascular events, according to a study published in the February 7 issue of JAMA.

According to background information in the study, a large body of evidence supports a central role for lowering levels of LDL-C in the prevention of atherosclerotic cardiovascular disease. “Randomized controlled trials have established that statin-mediated reductions in LDL-C have a favorable effect on the incidence of cardiovascular events. As a result, LDL-C lowering has become an integral component of therapeutic strategies in the prevention of cardiovascular disease. In particular, the use of statins has become widespread.”

Stephen J. Nicholls, M.B.B.S., Ph.D., and colleagues from the Cleveland Clinic, “investigated the relationship between changes in lipoprotein levels and atheroma volume [lipid deposits in the inner lining of the artery that can obstruct blood flow] in patients with coronary artery disease (CAD) who were treated with statins.” The researchers investigated the role of statin-induced reductions in atherogenic lipoproteins such as LDL-C and increases in HDL-C on the rate of atheroma progression. A total of 1,455 patients from four clinical trials were included. The patients underwent serial assessment of atheroma burden using intravascular ultrasonography. The average age of the patients was 57.6 years; 73 percent were men; 92 percent were white; the average body mass index was 30; 24 percent were current smokers; 76 percent had a history of hypertension; and 19 percent had a history of diabetes.

“The lipid changes translated to a mean [average] reduction in LDL-C of 23.5 percent and an increase in HDL-C by 7.5 percent, resulting in a reduction in LDL-C/HDL-C ratio of 26.7 percent. Changes in all lipid parameters, except lipoprotein(a), with statin therapy were significant,” the authors found. “Substantial atheroma regression (5 percent or more reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 milligrams per deciliter) during treatment and percentage increases of HDL-C greater than the mean (7.5 percent). No significant differences were found with regard to clinical events.”

“These findings may have important implications for the management of a patient with symptomatic atherosclerotic cardiovascular disease. The finding that the beneficial effect of statins on the rate of plaque progression is derived from both reducing LDL-C and increasing HDL-C complements the previous reports that the benefit of statins on both plaque progression and clinical events may be derived in part by anti-inflammatory properties. The findings also provide further evidence to support the atheroprotective properties of HDL-C and therapeutic interventions that increase its levels,” the authors write.

“Although it remains to be determined whether the atherosclerotic regression associated with changes in lipid levels observed in this study will translate to meaningful reductions in clinical events, the findings suggest that modifying the levels of both detrimental and protective lipids should be an important objective in the management of patients with established CAD,” the authors conclude.


(JAMA. 2007;297:499-508.)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Contact: Natalie Guzzo
JAMA and Archives Journals

Management Of Urethrocutaneous Fistula Following Hypospadias Repair

UroToday – With such a high prevalence of about 1 in 300 boys, those surgeons tasked with hypospadias repair face significant challenges as complications occur in up to 45% of cases. Among them, perhaps the most frustrating and widely discussed remains urethrocutaneous fistula following hypospadias repair. We evaluated our experience with this complication and its eventually successful management at our institute over an 11 year period.

Urethrocutaneous fistula complicating the initial repair occurred in 7% (n=123) of our patients. These were anterior in 34% (n=40), middle in 51% (n=60) and posterior in 15% (n=17). Assuming that all procedures were performed with meticulous care, the type of primary repair did not seem to have direct influence or effect on the development of a subsequent fistula.

Successful repair occurred in 73% of 117 cases on the first attempt, but noted undiagnosed distal obstruction in the form of meatal stenosis or anterior urethral stricture in 27 cases and 4 of the 31 cases repaired for the second time. Our study population revealed that recurrent urethrocutaneous fistula was more common in those patients with a posterior fistula, simple repair or with evidence of anterior urethral obstruction.

Of interest, 35 of the initial fistulas were coronal in location, 9 of the second fistulas and just 1 of the third. Simple repair was performed in 23 (66%) of the first and 4 (44%) of the second fistulas. Recurrent coronal fistulas following the first repair occurred in 4 (17%) of 23 simple repairs and 2 of the 12 complex repair. For coronal fistula requiring a second repair, 5 were repaired using simple technique with no recurrence and 4 were using complex technique with 1 recurrence.

A point to note was that among the anterior fistulas, the coronal site occurred in more than 80% of the cases. It seems possible that glans undergoes repeated minor episodes of lateral tension during erection, resulting in gradual thinning and splaying of the proximal glans and distal shaft with subsequent fistula formation. Alternatively this may represent a persistent weak point due to the abnormal development of the glans and corpora cavernosa in boys with hypospadias.

Whilst parents and patients need to be made aware of urethrocutaneous fistulas complicating hypospadias repair, this review suggests that they should also be encouraged that this may be satisfactorily addressed albeit after more than one surgical procedure.

A. J. A. Holland, M. Abubacker, G. H. H. Smith, and D. T. Cass as part of Beyond the Abstract on UroToday

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Preventing Falls May Be Key To Avoiding Disability In Elderly

Physical inactivity, depression and falls all increase risk of developing a disability in later life. But targeting falls may be a particularly effective way to reduce the nation’s disability levels, according to a new study.

Fall-prevention efforts that combine education about risks with exercise, home safety and health assessments offer the most promise, at least in the short run, found researchers led by Vicki Freedman, Ph.D., a professor at the University of Medicine and Dentistry of New Jersey.

Freedman and her colleagues compared three strategies to reduce late-life disability: increasing physical activity, identifying and treating depression and avoiding falls. Their findings, published in the current issue of The Milbank Quarterly, arise from a review of more than 100 intervention studies.

The review found that fall prevention efforts targeted at frail adults can reduce the risk of falling and related injuries by about 25 percent. Community-wide efforts that have been tested abroad were shown to reduce fall-related fractures by 6 percent to 33 percent.

“Both medical and environmental aspects of disability need to be addressed in a disability prevention program,” Freedman said. “Approaches that recognize the complexities of disability appear to be more successful than those that address only a single factor.”

About one-third of people aged 65 or older – or nearly 12 million people – experience falls, said Freedman. Of these, about 20 percent to 25 percent experience severe injuries or limitations.

Traditional health insurance programs may address medical aspects of a disability, but they rarely fund home safety changes or assistive technologies that may help an older adult live independently. The researchers call for additional research that considers how best to finance and deliver a multicomponent disability prevention program.

“Ideally, such an effort should consider not only which components to target, but also which audiences to target – older adults, their families, providers or perhaps entire communities.”

Freedman said she was surprised how little evidence she and her colleagues could find about the likely long-term effects of different intervention strategies. Most studies lasted less than a year. This scarcity of evidence is significant, she said, because conclusions about the long run could be very different.

Jon Pynoos, Ph.D., co-director of the Fall Prevention Center of Excellence, said that the review correctly identified medical risk assessment/management, physical activity and environmental modifications as the “big three” interventions capable of significantly reducing falls.

“Now we need to create ‘real-world’ programs that combine these elements and make them available to persons at moderate to high risk of falls who need them,” he said.

Pynoos said that one challenge is coordinating components from various fields – such as medicine, exercise and home modifications – with different eligibility requirements, reimbursement systems and approaches. It is also important to understand what “dose” effect or level of each intervention is needed to have an impact, he said.

“At the Fall Prevention Center of Excellence, we are working to create sustainable community-based programs that will serve as models that can be replicated in various settings,” Pynoos said.

Freedman VA, et al. Promoting declines in the prevalence of late-life disability: comparisons of three potentially high-impact interventions. The Milbank Quarterly 84(3), 2006.

Health Behavior News Service

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Washington, DC 20009
United States

Best Of Care For Pet Ferrets – British Veterinary Association

National Ferret Day on 5 May provides a timely reminder about the availability of the BVA Animal Welfare Foundation’s (BVA AWF) practical guide designed to enable owners to provide the very best of care for their pet ferrets. Produced in association with the Ferret Education & Research Trust (FERT), the ‘Caring for your ferret’ leaflet reflects the growing popularity of these intelligent and curious animals as household pets.

Carl Padgett, Chair of the BVA AWF Trustees, commented:

“The ‘Caring for your ferret’ leaflet covers the basics such as housing, feeding, health care and toilet training. It also offers advice on ‘ferret-proofing’ your home and garden, advice on games – ferrets particularly love hide-and-seek – and, very importantly, breeding and neutering as well as vaccination against canine distemper should owners be tempted to take their ferret for a walk on a lead and harness.”

The growing popularity of ferrets was highlighted in a recent survey which showed that almost half of owners acquired their ferret in the last five years and a significant majority of ferrets were now kept as pets rather than working animals.

“A high level of commitment and care is needed when taking on any pet and our guide should ensure that even the novice owner has all the information necessary to ensure their ferret’s health and welfare,” Mr Padgett added.

National Ferret Day aims to ensure issues such as welfare, care, nutrition and ownership are all highlighted in a positive light and to educate the public to respect these animals.

Speaking on behalf of the Trustees of FERT Ian Kearns said:

“One of FERT’s major concerns is that many ferrets are now ending up in rescue centres, because people haven’t read up on them before taking on one. We’d urge anyone to consider a ferret as a pet – but do your homework first, make sure you understand their housing and dietary needs, and of course register with a vet. As well as vaccination, your vet can also microchip your ferret.

“FERT is delighted to once again team up with the BVA AWF to publicise ferret care and welfare and to promote the ‘Caring for your ferret’ leaflet.”

‘Caring for your ferret’ is available to download from the BVA AWF website at bva-awf. Veterinary practices can obtain batches of leaflets for the waiting room by emailing the BVA AWF at bva-awfbva.


1. The BVA Animal Welfare Foundation is the veterinary profession’s charity committed to improving the welfare of animals through veterinary science, education and debate.

2. ‘Caring for your ferret’ is one of a series of BVA AWF leaflets designed to assist pet owners. Other leaflets include:

- Pets and poisons: keeping your animals safe
- What makes my pet happy?
- Taking your pets abroad: your guide to diseases encountered abroad
- Ornamental fish keeping
- An introduction to goat keeping

All BVA AWF literature can be downloaded.

3. Information on the Ferret Education and Research Trust

4. Information on the 2009 National Ferret Census

British Veterinary Association

Osiris Receives Approval For Prochymal Expanded Access Program In Canada

Osiris Therapeutics, Inc. (NASDAQ:OSIR) today announced it has received approval from Health Canada to initiate a pediatric expanded access treatment program for Prochymal, making the investigational stem cell product more readily available to children with life-threatening Graft vs. Host Disease (GvHD). Earlier this year the U.S. Food and Drug Administration became the first regulatory agency to take this action, making Prochymal available to children in the United States.

To learn more, pediatric transplant physicians are invited to meet with members of the Prochymal expanded access team December 6-8 at the 50th American Society of Hematology Annual Meeting and Exposition (Booth 385).

Prochymal is a formulation of adult mesenchymal stem cells designed to provide therapeutic benefit by controlling inflammation, promoting tissue regeneration, and preventing scar formation. Prochymal recently completed enrolling a Phase III trial for steroid refractory GvHD and is currently enrolling patients in a Phase III trial for Crohn’s Disease. Late last year Osiris reported data evaluating Prochymal as a rescue therapy in pediatric patients with severe GvHD. In that study, the drug completely resolved life-threatening GvHD in 58% of children who had otherwise exhausted available treatment options.

“The results for Prochymal in pediatric patients with severe GvHD have thus far been very encouraging, and as a participating principal investigator in the Phase III trial for steroid-refractory GvHD, my experience treating patients with Prochymal has been a positive one,” said Andrew Daly, M.D., Clinical Professor, Department of Medicine and Oncology at the University of Calgary, Canada. “With the implementation of this expanded access program, Osiris confirms its global commitment to the field of GvHD, a disease which is a significant unmet medical need.”

Under the expanded access program, children 2 months to 17 years in age inclusive with Grades B-D acute GvHD not responsive to steroids are eligible for treatment. For further eligibility criteria or information e-mail prochymalosiris.

In November, Osiris and Genzyme Corp. announced a strategic alliance for the development and commercialization of Prochymal. Under the terms of the agreement, Osiris will commercialize Prochymal in the United States and Canada, and Genzyme will commercialize the treatment in all other countries.

About Prochymal

Prochymal is a preparation of mesenchymal stem cells specially formulated for intravenous infusion. The stem cells are obtained from the bone marrow of healthy adult donors. Prochymal is currently being evaluated in three, double-blind, placebo controlled Phase III studies, including steroid refractory GvHD, acute GvHD, and Crohn’s disease. Prochymal has been granted Fast Track status by FDA for all three of these indications. Prochymal also obtained Orphan Drug status by FDA and the European Medicines Agency for GvHD. Prochymal is also being studied in Phase II trials for the treatment of COPD, type 1 diabetes, and acute myocardial infarction.

About Osiris Therapeutics

Osiris Therapeutics, Inc. is a leading stem cell therapeutic company focused on developing products to treat medical conditions in the inflammatory, orthopedic and cardiovascular areas. Prochymal is being evaluated in Phase III clinical trials for three indications, including acute and steroid refractory Graft versus Host Disease and also Crohn’s disease, and is the only stem cell therapeutic currently designated by FDA as both an Orphan Drug and Fast Track product. Furthermore, Prochymal is being developed for the repair of heart tissue following a heart attack, the protection of pancreatic islet cells in patients with type 1 diabetes, and the treatment of chronic obstructive pulmonary disease. The Company’s pipeline of internally developed biologic drug candidates under evaluation also includes Chondrogen for arthritis in the knee. Osiris is a fully integrated company, having developed capabilities in research, development, manufacturing, and distribution of stem cell products. Osiris has also formed a partnership with Genzyme Corp. for the development and commercialization of Prochymal and Chondrogen in countries outside the United States and Canada. Osiris has developed an extensive intellectual property portfolio to protect the company’s technology including 47 U.S. patents each having one or more foreign counterparts. Osiris, Prochymal and Chondrogen are registered trademarks of Osiris Therapeutics, Inc. More information can be found on the company’s website, www.Osiris.

Forward-Looking Statements

This press release contains forward-looking statements. Forward-looking statements include statements about our expectations, beliefs, plans, objectives, intentions, assumptions and other statements that are not historical facts. Words or phrases such as “anticipate,” “believe,” “continue,” “ongoing,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project” or similar words or phrases, or the negatives of those words or phrases, may identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. Examples of forward-looking statements include, but are not limited to, statements regarding the following: our product development efforts; our clinical trials and anticipated regulatory requirements and the ability to successfully navigate these requirements; the success of our product candidates in development; status of the regulatory process for our biologic drug candidates; implementation of our corporate strategy; our financial performance; our product research and development activities and projected expenditures, including our anticipated timeline and clinical strategy for Prochymal, Chondrogen and our other MSC and biologic drug candidates; our cash needs; patents and proprietary rights; the safety and ability of our potential products to treat disease and the results of our scientific research; our plans for sales and marketing; our plans regarding our facilities; types of regulatory frameworks we expect will be applicable to our potential products; and results of our scientific research. Forward-looking statements are subject to known and unknown risks and uncertainties and are based on potentially inaccurate assumptions that could cause actual results to differ materially from those expected or implied by the forward-looking statements. Risks and uncertainties related to the Collaboration Agreement with Genzyme include, among others: typical business transactional risks; risks related to product development and clinical trial design, performance and completion; uncertainty of the success of Prochymal and Chondrogen in clinical trials and their ability to treat disease; Genzyme’s early termination and opt-out rights; the ability of Osiris and Genzyme to successfully navigate regulatory requirements and to manufacture and commercialize products; and the uncertainty as to the ability of the parties to successfully perform under the collaborative arrangement and for Osiris to earn milestone and royalty payments thereunder. Our actual results could differ materially from those anticipated in forward-looking statements for many reasons, including the factors described in the section entitled “Risk Factors” in our Annual Report on Form 10-K and Quarterly Reports filed on Form 10-Q, with the United States Securities and Exchange Commission. Accordingly, you should not unduly rely on these forward-looking statements. We undertake no obligation to publicly revise any forward-looking statement to reflect circumstances or events after the date of this press release or to reflect the occurrence of unanticipated events.

Scientists Decode Genomes Of Diverse TB Isolates

An international collaboration led by researchers in the US and South Africa announced the first genome sequence of an extensively drug resistant (XDR) strain of the bacterium Mycobacterium tuberculosis, one linked to more than 50 deaths in a recent tuberculosis (TB) outbreak in KwaZulu-Natal, South Africa. As part of this work, genomes of multi-drug resistant (MDR) and drug sensitive isolates were also decoded. Initial comparisons of the genome sequences reveal that the drug-resistant and drug-sensitive microbes differ at only a few dozen locations along the four-million-letter DNA code, revealing some known drug resistance genes as well as some additional genes that may also be important to the spread of TB. The researchers have taken an unusual step of immediately sharing both the genome sequence and their initial analysis far in advance of submitting a scientific paper, in order to accelerate work on drug-resistant TB by researchers around the world.

“Tuberculosis is a major threat to global public health that demands new approaches to disease diagnosis and treatment,” said Megan Murray, one of the project’s principal investigators, an associate member of the Broad Institute of MIT and Harvard and an associate professor at the Harvard School of Public Health. “By looking at the genomes of different strains, we can learn how the tuberculosis microbe outwits current drugs and how new drugs might be designed.”

“Genome information is a powerful tool for understanding the biology of infectious disease, such as tuberculosis,” said Eric Lander, founding director of the Broad Institute of Harvard and MIT. “It is important that genomic data be made immediately available, particularly to researchers in areas most heavily burdened by disease.”

“The sequenced strain is responsible for the vast majority of the more than 300 XDR cases identified thus far in the KwaZulu-Natal province of South Africa,” said Willem Sturm, one of the project’s principal investigators and a leading researcher of the XDR epidemic in KwaZulu-Natal, dean of the Nelson Mandela School of Medicine, and director of the MRC Genital Ulcer Disease Research Unit at the University of KwaZulu-Natal. “Genetic characterization of this strain is essential for developing tools to get this epidemic under control.”

Globally, tuberculosis (TB) is a major cause of infectious disease deaths. Nearly 2 billion people, comprising roughly one third of the world’s population, are thought to carry M. tuberculosis, the culprit bacterium. Major obstacles to controlling the disease stem from the microbe’s ability to evade current treatments, which typically require prolonged use by patients and are often not curative. MDR strains, for example, are resistant to two of the most effective first-line TB drugs, and XDR strains can circumvent first-line as well as some second-line drugs. Adding to the problem, inefficient diagnostic methods for TB make it difficult for doctors to determine whether an individual harbors a drug-resistant strain, often delaying proper therapy.

To shed light on the genetic changes that mediate drug resistance, an international team of scientists undertook a large-scale effort to sequence the genomes of drug sensitive, MDR, and XDR TB isolates of a strain responsible for the current XDR-TB epidemic in KwaZulu-Natal, South Africa. This strain corresponds to one found in patients in Tugela Ferry, a rural town in KwaZulu-Natal that has recently experienced a severe outbreak of XDR TB among patients infected with the human immunodeficiency virus (HIV). There, 52 of 53 people infected with this strain died. The research reflects a collaboration among researchers in the Microbial Sequencing Center at the Broad Institute of Harvard and MIT, Megan Murray of the Harvard School of Public Health, and Willem Sturm and his colleagues at the Nelson Mandela Medical School in South Africa.

The draft genome sequences of the various TB strains each cover roughly 95% of the M. tuberculosis genome. Comparing the DNA sequences in these regions allows the researchers to pinpoint the key differences among them, shedding light on the genetic factors that contribute to TB drug resistance. Strikingly, comparisons of the draft sequences reveal surprisingly few genetic differences among the drug sensitive, MDR and XDR strains: there are only a few dozen small DNA changes. Some of these differences are located in genes known to be involved in TB drug resistance, while others are found in novel genes, whose roles have not been previously investigated. Some of these genes may represent new drug-resistance genes, while others may simply contain random mutations.

“That a limited set of genetic differences separates one TB strain from another is important,” said James Galagan, the associate director of microbial genome analysis at the Broad Institute. “With the analysis of additional XDR strains, it should be feasible to systematically unravel the biological significance of each genetic variation.”

“These results also lay the groundwork for the development of a rapid diagnostic test for TB,” said Murray. “Such a test would enable more rapid and accurate diagnoses, and help to prevent the spread of TB – especially the most virulent strains.”

A significant fraction of the new TB research was accomplished through the use of a powerful new technology for decoding DNA. That approach, based on the principle of single-molecule sequencing, makes it possible to read hundreds of millions of DNA letters simultaneously.

“New technologies for sequencing DNA can accelerate the pace of genomic research, particularly for infectious disease,” said Bruce Birren, director of the Microbial Sequencing Center at the Broad Institute. “It is important that these technologies also be made available to researchers in the field, where they are needed most.”

Importantly, all of these data have been released far in advance of publication and can be accessed by TB researchers worldwide, helping to spark work on an infectious disease that constitutes a leading threat to global public health. In the next phase of their work, the scientists plan to refine the draft genome sequences and their comparative analysis, and expand the scope of their research to include additional TB strains.

Data access
These data can be accessed through the Broad Institute website, at, or through the TB database, tbdb.

About the Microbial Sequencing Center

The Broad Institute’s Microbial Sequencing Center is one of two centers funded by the National Institutes of Allergy and Infectious Disease to serve as a national resource for sequencing and analyzing microbial genomes, including those of pathogenic fungi, bacteria, parasites, vectors and related species. The publicly available data are the basis for research on pathogenicity, drug resistance, disease transmission, and vaccine development, and will contribute to global efforts to improve detection, prevention and treatment of microbial infections.

About the Broad Institute of Harvard and MIT

The Broad Institute of Harvard and MIT was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease.

The Institute is a research collaboration that involves faculty, professional staff and students from throughout the MIT and Harvard academic and medical communities. It is jointly governed by the two universities.

Organized around Scientific Programs and Scientific Platforms, the unique structure of the Broad Institute enables scientists to collaborate on transformative projects across many scientific and medical disciplines.

About the Harvard School of Public Health

Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 900-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

First Patient Enrolled In ‘CONNECT’ Clinical Trial

Avinger, Inc., a medical device company focused on the development of innovative devices to combat peripheral artery disease, announces the enrollment of the first patient in the CONNECT (Chronic TOtal OcclusioN CrossiNg with thE WildCat CatheTer) clinical trial. The CONNECT trial is a prospective, multi-center, non-randomized study intended to evaluate the Wildcat Catheter’s ability to cross chronic total occlusions in femoropopliteal lesions. Patients with peripheral artery disease may have chronic total occlusions which are sometimes difficult to treat with endovascular therapy resulting in either bypass surgery or amputation.

The ability to cross chronic total occlusions (CTOs) enables subsequent endovascular treatment of peripheral artery disease and is directly related to acute procedural success and favorable long-term outcomes. The Wildcat Catheter crosses CTO lesions by creating a small channel through the blockage using retractable spiral wedges creating a “corkscrew” effect enabling further treatment of the lesion with therapeutic devices. The Wildcat Catheter received FDA 510(k) clearance in February 2009 for use as a guidewire support device to access discreet areas of the vasculature. Avinger is conducting this study to secure FDA clearance for an indication specific to crossing CTOs.

“We are very excited by this new technology,” said Dr. Thomas Davis of St. John Hospital and Medical Center, who enrolled the first patient in the CONNECT trial. “If we weren’t able to cross this CTO with the Wildcat, the only other option for this patient would have been a surgical bypass or amputation. With the help of this technology we will hopefully be able to change the paradigm of treatment from surgical to endovascular.”

The CONNECT study will evaluate 88 PAD patients with femoropopliteal CTO lesions at 15 centers in the US. Patients will be followed for 30 days post procedure and an independent group of physicians will review the angiography results to determine crossing efficacy and safety. Conditional FDA approval to conduct this study was received on August 11, 2010. Co-Principal investigators for the trial are Dr. Thomas Davis of St. John Hospital and Medical Center in Detroit, Michigan and Dr. Laiq Raja of El Paso Cardiology Associates, P.A. and Providence Memorial Hospital in El Paso, Texas.

“Avinger was created to develop technologies that change the way vascular disease is treated today,” said Avinger CEO John B. Simpson, PhD, MD. “The CONNECT trial will provide clinical data to help guide physicians in the use of the Wildcat and provide expanded treatment options for PAD. We hope that Avinger can play a key role in helping patients facing an amputation keep their leg.”

Source: Avinger, Inc

Cost Change Proposal Insufficient To Change Draft Recommendation By NICE On Everolimus For Advanced Renal Cell Carcinoma

In its latest draft guidance, NICE has been unable to recommend everolimus (Afinitor, Novartis) for the second line treatment of advanced renal cell carcinoma because it does not provide enough benefit to patients to justify its high cost.

Following publication of the first Final Appraisal Determination (FAD) the manufacturer of everolimus, Novartis, submitted an amended patient access scheme. The consultation was therefore suspended to allow the Appraisal Committee to consider the additional evidence on the total costs of use of everolimus in the NHS. This is the second FAD for this appraisal and the draft guidance is now with consultees, who have the opportunity to appeal against it. NICE has not yet issued final guidance to the NHS.

Commenting on the draft recommendations, Sir Andrew Dillon, Chief Executive at NICE said:”NICE asked the independent Appraisal Committee to consider the newly amended patient access scheme and a further cost effectiveness analysis that NICE asked the manufacturer to provide. However, the committee felt that there was still too much uncertainty around how cost effective everolimus is to enable the committee to recommend the drug.

“We know that patients with renal cancer want to try all the treatment options and are disappointed not to be able to recommend everolimus as a second line treatment option. However, we have to ensure that the money available to the NHS, for treating cancer and other conditions is used to best effect, particularly when NHS funds, like the rest of the public sector, is under considerable financial pressure.”

Novartis has asked NICE not to disclose the content of the revised patient access scheme.

About the appraisal

1. Further information is available on the Renal cell carcinoma (second line metastatic) – everolimus page.

2. Renal cell carcinoma is a kidney cancer (tumour) that starts in cells lining the small tubes that help to make urine. In advanced disease, the tumour has spread inside the kidney, but may or may not have spread to nearby lymph glands. In metastatic renal cell carcinoma, the tumour has spread beyond the lymph glands to other parts of the body.

3. Evidence suggests that everolimus increased survival by more than 3 months compared with best supportive care.

4. The manufacturer of everolimus has agreed a patient access scheme with the Department of Health in which the first treatment pack of everolimus is free to the NHS and following treatment packs cost ВЈ2,822 (a 5% acquisition cost discount). A revised patient access scheme was subsequently agreed, the details of which are confidential.

5. The number of people diagnosed with advanced RCC each year is less than 4000 and those eligible for everolimus (that is received first-line sunitinib and still fit enough to receive a second-line treatment) would be lower.

6. The committee felt that everolimus did fit the criteria to be considered under end of life. However, when taking into account both the value of the ICERs and the uncertainty around the ICERs, the Committee concluded that it could not recommend everolimus for the second-line treatment of advanced renal cell carcinoma as a cost-effective use of NHS resources.



View drug information on Afinitor.

Also In Global Health News: Kyrgystan Appeals For Aid; TB In Western Pacific; Pakistan Water Crisis; Zimbabwe Medical Fees; Measuring TB

Kyrgystan Asks For $1.2B In Aid To Rebuild Country

“Kyrgyzstan’s government appealed to an international donors conference Tuesday for $1.2 billion in aid to rebuild the country after months of political and ethnic violence,” the Associated Press reports. The conflict “ravaged major markets and businesses, depriving the south of important sources of employment and economic development.” The AP adds that “the most immediate attention is being paid to the humanitarian situation in the south, where thousands have been forced to take refuge in tents or live with relatives” (Leonard, 7/27). In June, the U.S. committed $6.5 million in humanitarian aid to the country (Kaiser Daily Global Health Policy Report, 6/17).

TB Efforts In Western Pacific Need More Financial Support

Xinhua reports that the WHO “warned Monday that the Western Pacific Region’s gains in tuberculosis control over the last decade would be lost” without more financial and technical support. The epidemic concentrates in vulnerable populations with limited access to health care, according to Shin Young-soo, WHO regional director for the Western Pacific. Shin’s remarks were made at the Stop TB Technical Advisory Group meeting, which also discussed HIV, which he said is a “major threat and has the potential to reverse the gains achieved by the TB control efforts” (7/26).

AP/Washington Post Examines Pakistan’s Water Crisis

A growing population and inefficient farming practices are causing a “severe [water] crisis” in Pakistan, according to the Associated Press/Washington Post. Nearly 630 children die each day and “up to a third of Pakistan’s 175 million people lack safe drinking water,” the news service reports, citing a study by the Woodrow Wilson International Center for Scholars. The AP/Washington Post reports that Pakistan’s water availability per person dropped from 5,000 cubic meters in 1947 to 1,000 today and notes that “at least” 90 percent of the country’s water is used for farming (7/26).

Medical Fees Create Barriers To Care For Pregnant Women In Zimbabwe

Health service fees are “opening a growing gap between policy and implementation in maternal health” in Zimbabwe where the government policy is that pregnant women, new mothers and infants should receive free care, Inter Press Service reports. “Expecting mothers are required to pay a 50 U.S. dollar booking fee at clinics and government hospitals, but this is … an amount many here cannot afford.” In some cases, women are told they cannot leave the hospital or are denied documents needed to get a birth certificate until they pay their bills, the news service reports, adding that “the country’s rapid economic decline in the past decade has compelled health institutions to raise their own revenue to meet costs.” The article also examines Zimbabwe’s progress toward Millennium Development Goals on child and maternal health and a “proliferation” of traditional medicine because of women’s inability to access formal health care (Banda, 7/26).

MODS Culture Method Shows Promise In Diagnosing TB In Children

“The microscopic-observation drug-susceptibility (MODS) culture method, using duplicate gastric-aspirate specimens, may be the best diagnostic test for pulmonary tuberculosis in high-risk children in a resource-poor setting, according to research published online” Tuesday in Lancet Infectious Diseases, HealthDay/ModernMedicine reports. Researchers from Tulane University compared 218 children, from a low-income area in Lima, Peru, with suspected pulmonary tuberculosis with 238 controls. Twenty-two cases had “at least one positive M tuberculosis culture,” and the researchers found that MODS was “more sensitive” than the standard Lowenstein-Jensen culture, diagnosing 20 of 22 patients compared with 13 of 22 patients (7/26).

This information was reprinted from globalhealth.kff with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Global Health Policy Report, search the archives and sign up for email delivery at globalhealth.kff.

© Henry J. Kaiser Family Foundation. All rights reserved.

Transient ischemic attack patients receive less aggressive attention than those with stroke

Transient ischemic attack (TIA) patients receive less aggressive diagnostic testing, treatment and education compared to
stroke patients, which is a missed opportunity to prevent permanent disability or death, researchers reported at the American
Stroke Association’s International Stroke Conference 2005.

“There needs to be a paradigm shift in the way the public and physicians look at TIA,” said study lead author Bhuvaneswari
Dandapani, M.D., medical director of the stroke center at Holmes Regional Medical Center in Melbourne, Fla. “TIA is perceived
as a much less serious condition than stroke by the public and by professionals.”

About one-third of people who have TIAs, which are sometimes called “mini-strokes” will have a major stroke within five years
unless they have preventive therapy.

“The public fails to understand that experiencing a TIA is a medical emergency and those who have symptoms should seek
attention in the emergency room,” Dandapani said. “For physicians, a TIA represents an opportunity to prevent a catastrophic

TIA symptoms are the same as stroke symptoms but last only a short time:

– Sudden numbness or weakness of the face, arm or leg, especially on one side of the body;

– Sudden confusion, trouble speaking or understanding;

– Sudden trouble seeing in one or both eyes;

– Sudden trouble walking, dizziness, loss of balance or coordination; and

– Sudden, severe headache with no known cause.

Symptoms occur suddenly and vary widely, with an episode lasting from a few minutes to a few hours.

The retrospective study evaluated diagnostic tests, therapy and education of 91 TIA patients compared to 94 stroke patients.
Patients’ average age was 73; most were Caucasian and 58 percent were women. For almost 90 percent of the TIA patients, the
TIA was their first. Of the stroke patients, 36 percent had a previous TIA or stroke, while 64 percent were first strokes.

TIA patients received less diagnostic testing than stroke patients, but nearly all TIA and stroke patients underwent a brain
CT. MRI was performed on 69 percent of TIA patients and 72 percent of stroke patients.

Ultrasound tests, which are important in identifying stroke risk and planning therapeutic interventions, were performed in a
much lower percentage of TIA patients than stroke patients. Of the TIA patients, 54 percent underwent carotid Doppler
ultrasound compared to 76 percent of stroke patients. Of the TIA patients, 34 percent had echocardiography compared to 60
percent of stroke patients. Transesophageal echocardiography was performed on 1 percent of TIA patients compared to 12
percent of stroke patients, while 5 percent of TIA patients underwent transcranial Doppler compared to 9 percent of stroke

“All the diagnostic tests performed on stroke patients should be performed on TIA patients, because TIA represents a ticking
time bomb,” Dandapani said.

In the evaluation of therapy, the study found about 60 percent of both TIA and stroke patients were discharged on the
antiplatelet agent aspirin. Anticoagulant therapy was similar in both groups. ACE inhibitor therapy was prescribed in 26
percent of stroke patients and in 12 percent of TIA patients.

The rate of documented stroke education at discharge for TIA patients was 35 percent versus 67 percent for stroke patients.

In light of the findings, Dandapani recommended improved public education about TIA and stroke and improved diagnosis and
therapy for TIA.

Dandapani plans to extend this TIA research to different regions of the country and to different types of hospitals. A new
unit at Holmes Regional Medical Center will meet the needs of TIA patients, she said. All appropriate systems are in place
for diagnosis, treatment and education.

Co-authors are James Palermo, M.D.; Todd Schell, OTR/L, M.S.; James Gebel, M.D. and Vijay Vasudevan, a senior at the
University of Florida.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are
solely those of the study authors and do not necessarily reflect association policy or position. The American Heart
Association makes no representation or warranty as to their accuracy or reliability.

Abstract 76

NR05-1006 (ISC05/Dandapani)

Note: Presentation time is 5 p.m., CST, Thursday, Feb. 3, 2005.

Bridgette McNeill – bridgette.mcneillheart
American Heart Association