Early TIPS for Ascites Study Seeks to Improve Survival

  • Wednesday, August 31, 2011
  • Posted by HCV New Drugs
  • File Under ,

September issue of Gastroenterology

COMMENTARY
Early TIPS for Ascites Study Seeks to Improve Survival
BY DR. THOMAS D. BOYER

The possibility that we can improvethe quality and length of life for liver disease patients, without a transplant, is one of the most exciting potentia lopportunities in our field today. Ascites,the most common complication from cirrhosis, develops in 50% of patients within10 years.1 Development of ascites reflects decompensation of the liver and is associated with an increase in morbidity and mortality.

Initially, the ascites is usually controlled easily with diuretics, but as the liver disease worsens, higher and higher doses of diuretics are required to maintain patient comfort. Eventually, diuretic treatment fails and the patient is diagnosed with refractory ascites. The current standard of care for refractory ascites consists of large volume paracentesis (LVP), coupled with an aggressive pharmacotherapy regimen.

Transjugular intrahepatic portosystemicshunt (TIPS) therapy is regarded as the last line of defense, a bridge to liver transplantation.

However, these conclusions are based on trials in which bare stents were used to create the TIPS. With covered stents that are now available, better outcomes might be possible.

Interventional radiologists and hepatologists have come together in an international trial to determine if TIPS intervention can increase transplant-free survival compared to LVP when performed earlier in the ascitic patient population.

Previous studies comparing TIPS to LVP must be revisited. Conducted in the1990s and early 2000s, these studies may have failed to consistently demonstrate increased life expectancy for three reasons.

First, mostly end-stage patients with refractory ascites were included. Second, neither therapy changes the underlying liver disease, a reason why most therapies, except transplant, have failed to show a survival benefit.

Finally, bare metal stents,which had a high failure rate, were the only option for TIPS therapy at the time.

This study is being conducted to evaluate whether newer technology like covered stents with a lower failure rate will address this last potential pitfall. The Early TIPS for Ascites Study is a randomized, multi-center study, sponsored by Gore Medical in collaboration with both hepatologists and interventional radiologists.

Given the nature of the TIPS referral pathway, the team approach will lead to better patient care, more coordinated medical management, and improved recruitment. The goal of the study is to determine whether patients with difficult-to-treat ascites benefit most from early TIPS therapy using a covered stent or from continued LVP,based on transplant-free survival.

This study has survival as its primary endpoint, in contrast to previous trials, which looked at control of ascites. There is little question that TIPS is better than LVP in controlling the ascites. But controlled trials have shown that use of TIPS is associated with more encephalopathy than alternative forms of therapy.1

What is unclear is the balance of these two factors and the over all impact on survival. This study will also differ from prior studies that focused on refractory ascites, because the Early TIPS forAscites Study protocol allows for enrollment of patients prior to reaching the refractory stage as defined by TheInternational Ascites Club. This is also the first study of its kind in which the Modelfor End-Stage Liver Disease score is used for patient selection and will also be tracked during follow-up as a study end point.

Previous studies comparing TIPS with bare metal stents to LVP in patients with refractory ascites had mixed findings.2 Yet arecent meta-analysis of these studies found that TIPS patients had significantly longer transplant-free survival than paracentesis patients.3 And a study published last year in the New England Journal of Medicine4 compared early TIPS intervention with a covered stent to pharmacotherapy/endoscopicband ligation in high-risk variceal bleeding patients, with positive results.

TIPS therapy is a minimally invasive procedure done with closed surgery, as only a small puncture is made in the jugular vein for insertion of the device. A TIPS creates a functional side-to-side portocaval shunt to route blood flow through the damaged liver and into the main blood vessels that carry blood back to the heart.

With the TIPS procedure, alternative treatments such as medications and paracentes is for ascites, and endoscopic treatment of varices, may possibly not be needed as often. Some reports have shown significant improvements in TIPS therapy when using a covered stent versus a bare metal stent.5,6

As one of the national principal investigators for the Early TIPS for Ascites Study, I believe that the possibility of prolonging patient lives is one of the most exciting new questions in TIPS therapy that we must answer. Most treatments for complications of portal hypertension improve the patient’s condition without affecting survival. We believe that if survival improves in the TIPS cohort, the paradigm for management of cirrhotic ascites might change significantly.

■THOMAS D. BOYER, M.D., is Director ofthe Arizona Liver Research Institute,Professor of Medicine, and Medical Director of the University Medical CenterLiver Transplant Program, University ofArizona College of Medicine, Tucson.References1. Hepatology 2005;41:386-400.2. Hepatology 2009;49:2087-107.3.
Gastroenterology 2007;133:825-34.4. N. Engl. J. Med. 2010;362:2370-9.5. Hepatology 2003;38:1043-50.6. Liver International 2007;27:742-7

IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis

Research

The complete article ;Download PDF

Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort

Katherine R Smith, Vijayaprakash Suppiah, Kate O'Connor, Thomas Berg, Martin Weltman, Maria Lorena Abate, Ulrich Spengler, Margaret Bassendine, Gail Mathews, William L Irving, Elizabeth Powell, Stephen Riordan, Golo Ahlenstiel, Graeme J Stewart, Melanie Bahlo, Jacob George, David R Booth and the International Hepatitis C Genetics Consortium (ihcgc)

Genome Medicine 2011, 3:57 doi:10.1186/gm273Published: 31 August 2011

Abstract (provisional)

Background
The hepatitis C virus (HCV) infects nearly 3% of the World's population, causing severe liver disease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin (PegIFN/R), which is effective in less than half of those infected with the most common viral genotype. Two IL28B single nucleotide polymorphisms (SNPs), rs8099917 and rs12979860, predict response to (PegIFN/R) therapy in treatment of HCV infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry, there are 6 common (more than 1%) haplotypes for IL28B, one tagged by rs8099917 minor allele, four tagged by rs12979860.

Methods
We used massively parallel sequencing of the IL28B and IL28A gene regions generated by polymerase chain reaction (PCR) from pooled DNA samples from 100 responders and 99 non-responders to therapy, to identify common variants. Variants that had high odds ratios and were validated were then genotyped in a cohort of 905 responders and non-responders. Their predictive power was assessed, alone and in combination with HLA-C.

Results
Only SNPs in the IL28B linkage disequilibrium block predicted drug response. Eighteen SNPs were identified with evidence for association with drug response, and with a high degree of confidence in the sequence call. We found that two SNPs, rs4803221 (homozygote minor allele positive predictive value (PPV) of 77%) and rs7248668 (PPV 78%), predicted failure to respond better than the current best, rs8099917 (PPV 73%) and rs12979860 (PPV 68%) in this cross-sectional cohort. The best SNPs tagged a single common haplotype, haplotype 2. Genotypes predicted lack of response better than alleles. However, combination of IL28B haplotype 2 carrier status with the HLA-C C2C2 genotype, which has previously been reported to improve prediction in combination with IL28B, provides the highest PPV (80%). The haplotypes present alternative putative transcription factor binding and methylation sites.

Conclusions
Massively parallel sequencing allowed identification and comparison of the best common SNPs for identifying treatment failure in therapy for HCV. SNPs tagging a single haplotype have the highest PPV, especially in combination with HLA-C. The functional basis for the association may be due to altered regulation of the gene. These approaches have utility in improving diagnostic testing and identifying causal haplotypes or SNPs.

The complete article is available as a provisional PDF.
The fully formatted PDF and HTML versions are in production.

Aug 31 Hepatitis New Ticker;Telaprevir Markedly Improves HCV Genotype 1 Cure Rates

New On The Blog
Hepatitis C-TMC435 ;MedivirAB Completed Enrollment of Three Global Phase 3 Trials
Video; Victrelis, and Incivek-2 new drugs to fight Hepatitis C
Hepatitis C; Response To Treatment Geno 3-fibrosis but not race encourages relapse

FDA Request That H&P Recall Povidone Iodine Prep Solutions W-other Multiple brands affected
Update;
Beleaguered wipe-maker hires new COO; prepares to reopen
H&P Industries hires former Abbott Laboratories executive to rebuild firm
A Wisconsin firm shut down after making and distributing contaminated alcohol wipes and other medical products blamed for infections and deaths has hired a new chief operating officer as officials work to reopen the company.

Todays News

Telaprevir Markedly Improves HCV Genotype 1 Cure Rates
From Journal Watch ; Journal Watch Gastroenterology
Atif Zaman, MD, MPH
Authors and Disclosures
Posted: 08/31/2011; Journal Watch © 2011 Massachusetts Medical Society

Abstract and Introduction
Abstract
Final results of phase III trials show that telaprevir plus standard therapy with peginterferon alfa-2a and ribavirin was more effective than standard therapy alone.

Introduction
Recently, telaprevir-based triple therapy (i.e., in combination with peginterferon alfa-2a and ribavirin) was approved for the treatment of chronic hepatitis C virus (HCV) infection. The final results of the international phase III trials for both treatment-naive and treatment-experienced patients with HCV genotype 1 infection are now available.

In the first of two industry-sponsored, double-blind, placebo-controlled trials, 1095 treatment-naive patients were randomized to receive either triple therapy for 12 weeks followed by peginterferon plus ribavirin for 12 weeks — or 36 weeks if HCV RNA was detectable at weeks 4 or 12 — (T12PR group); triple therapy for 8 weeks followed by peginterferon plus ribavirin for either 16 or 36 weeks (T8PR group); or peginterferon plus ribavirin for 48 weeks (PR group).

In the second trial, 663 treatment-experienced patients were randomized 2:2:1 to receive either triple therapy for the first 12 weeks followed by 36 weeks of peginterferon plus ribavirin (T12PR48 group), a 4-week lead-in of peginterferon plus ribavirin followed by 12 weeks of triple therapy and then 32 weeks of peginterferon plus ribavirin (lead-in T12PR48 group), or peginterferon plus ribavirin for 48 weeks (PR48 group). In both trials, doses were 750 mg every 8 hours for telaprevir, 180 µg weekly for peginterferon alfa-2a, and 1000–1200 mg daily for ribavirin. The primary endpoint was sustained virologic response (SVR).

For treatment-naive patients, SVR rates were higher in the T12PR and T8PR groups than in the PR group — 75% and 69% versus 44%; P<0.001. Although the numbers of patients who were black or had advanced fibrosis were small in the study cohort (7% and 20%, respectively), in both subgroups, SVR rates were higher in the telaprevir groups than the peginterferon plus ribavirin group. Among treatment-experienced patients, SVR rates for arms T12PR48, lead-in T12PR48, and PR48, respectively, were 83%, 88%, and 24% for previous relapse; 59%, 54%, and 15% for previous partial response; and 29%, 33%, and 5% for previous null response (P<0.001 for all comparisons).

In general, virologic failure in the telaprevir groups was attributable primarily to the development of drug resistance. In both studies, the telaprevir groups had higher rates of anemia, rashes, pruritus, and gastrointestinal problems than the peginterferon plus ribavirin group. Discontinuation of medications for any reason ranged from 10% to 15% for the telaprevir regimens and from 7% to 10% for the peginterferon plus ribavirin regimen

Comment
These companion studies demonstrate that telaprevir-based regimens are significantly more effective in HCV genotype 1–infected patients than peginterferon plus ribavirin alone — for both treatment-naive and treatment-experienced patients. Although more adverse events occurred in the telaprevir-treated groups, discontinuation rates were still relatively low. Overall, the best SVRs were seen in treatment-naive and prior-relapse patients (≥75%), followed by previous partial responders, treatment-naive blacks, and patients with advanced fibrosis (50%–60%), and last, previous null responders (30%). Therefore, caution should be exercised in treating null responders, especially since the majority of virologic failure leads to drug resistance.
References

Sexual Transmission of HCV Among HIV-Infected MSM, 2005-2010
This new report discusses the rates of sexual transmission of HCV among gay men already infected with HIV. How prevalent is it?
Morbidity & Mortality Weekly Report, August 2011
Abstract and Introduction
Characteristics of Case-Patients
Case-Control Study
Results of Phylogenetic Analyses
Editorial Note
References
Sidebar

Poxvirus vaccine is safe and decreases viral load in patients with chronic Hepatitis C
Poxvirus vaccine is safe, induces T-Cell responses, and decreases viral load in patients with chronic Hepatitis C, reports the latest issue of Gastroenterology.

Therapy for chronic hepatitis C has limited efficacy, adverse effects, and high costs.
Cohort and vaccine-based preclinical studies have indicated the importance of T-cell–based immunity in controlling viral infection.

TG4040 is a recombinant poxvirus vaccine that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B.

Dr François Habersetzer and colleagues from France performed a phase I clinical trial to assess the safety, immunogenicity, and early antiviral efficacy of TG4040 in patients with chronic hepatitis C.

In an open-label, dose-escalating study, patients with mild chronic hepatitis C (genotype 1) were assigned to 3 groups of 3 patients each.

All 3 doses of TG4040 were well tolerated
Gastroenterology


They received subcutaneous injections of 106, 107, or 108 plaque-forming units of TG4040 on study days 1, 8, and 15.
The team gave 6 additional patients the highest dose of vaccine.
Patients were followed for 6 months after the last injection.
T-cell–based and antibody responses and levels of HCV RNA were measured.
All 3 doses of TG4040 were well tolerated, without serious adverse events.
The researchers observed that vaccine-induced HCV-specific cellular immune responses in 33% of patients.

A transient decrease in circulating levels of HCV RNA was observed in 8 patients, in 5 patients, the lowest level of HCV RNA was observed on day 37, after the first injection.
The research team found that the most pronounced decrease in viral load occurred in 2 patients, who also had marked vaccine-induced T-cell responses.
Dr Habersetzer's team concludes, "In patients with chronic hepatitis C, the viral-vector–based vaccine TG4040 had a good safety profile, induced HCV-specific cellular immune responses, and reduced viral load."
"This vaccine should be investigated in further clinical studies, in combination with standard of care."
Gastroenterol 2011: 141(3): 890-89931 August 2011

Clinic may have exposed patients to HIV, hepatitis: How to stay safe
The former employee reportedly changed needles on these devices each time, but reused the rest of the devices - which may trap microscopic amounts of blood and cross-contaminate a patient, reported WMTV. Further, the insulin pen wasn't even supposed to be used on patients.

Spatial mapping of hepatitis C prevalence in recent injecting drug users in contact with services.
SUMMARY
In developed countries the majority of hepatitis C virus (HCV) infections occur in injecting drug users (IDUs) with prevalence in IDUs often high, but with wide geographical differences within countries. Estimates of local prevalence are needed for planning services for IDUs, but it is not practical to conduct HCV seroprevalence surveys in all areas. In this study survey data from IDUs attending specialist services were collected in 52/149 sites in England between 2006 and 2008. Spatially correlated...

Transplant

Changes To Distribution Of Livers For Transplant Proposed
Main Category: Liver Disease / Hepatitis
Also Included In: Transplants / Organ Donations
Article Date: 31 Aug 2011 - 1:00 PDT

Transplantation specialists have proposed changes to the allocation and distribution of organs used for liver transplants. The recommended policy modifications take into account the scarcity of available organs, ensuring rapid allocation and delivery of the organ to those most in need in order to reduce mortality for waitlisted patients. Details of the proposed model are available in the September issue of Liver Transplantation, a journal published by Wiley Blackwell on behalf of the American Association for the Study of Liver Diseases.

A number of diseases affect liver function, including hepatitis B and C, nonalcoholic fatty liver disease, and autoimmune liver disease. The severity of liver disease ranges from mild to more severe forms that are life-threatening. When the liver fails (end stage liver disease) and patient life is at risk for death, transplantation is the recommended option. However, the scarcity of donor organs is one of the greatest concerns for transplantation candidates and a challenge for clinicians who treat them. According to the Organ Procurement and Transplant Network (OPTN) there are more than 16,000 Americans on the waiting list to receive a liver as of August 2011.The current model in the U.S. defines allocation as the order of patients on a particular waiting list.

Since 2002, the transplantation community has used the Model for Endstage Liver Disease (MELD) score and length of time on waiting list to rank patients for allocation of the available liver. Distribution is the determination of the area to which a donor liver will be offered, and uses a local, regional, national system to distribute available livers for transplant.
The OPTN donation service area that is assigned to the organ procurement organization is the designated "local" region using this system.

In an examination of the allocation and distribution of livers for transplantation, the authors reviewed the system currently used to determine which patients receive organs for transplant and provided alternative models to promote a more equitable distribution. "Given the disparity between supply and demand of deceased donor livers, there will always be differences of opinion as to which patient should be transplanted first," said lead author Kenneth Washburn, M.D., with the University Transplant Center, a partnership of The University of Texas Health Science Center at San Antonio and one of its primary clinical partners, the University Health System. "Any system that redistributes organs from low-need to high-need areas will not please all stakeholders," he added.

The authors note that most deaths on the waiting list occur in patients with low MELD scores the largest patient group on the list and allocating organs to this group would not reduce the overall death rate due to the low and unpredictable individual mortality risk. Since the largest number of deaths on the waiting list cannot be prevented through organ allocation, the authors suggest a system should focus on patients with higher MELD scores who have the greatest risk of death.

Based on prior feedback from involved stakeholders, small incremental changes to the current system would be the best method for making allocation policy improvements. One potential next step, according to the authors, is moving from a "share 15" regional model to a "national 15" sharing model which would direct donated livers to waitlist patients with MELD score of 15 at the regional then national level before candidates at the local level whose MELD score is less than 15 would be offered a liver.

Another incremental change the authors propose is regional sharing for the sickest patients with high MELD scores (> 35). Redistribution of donated livers to this patient group results in a decrease in waitlist mortality for these patients who have the highest risk of death while awaiting a transplant. "We suggest focusing on amendments to organ distribution that decrease waitlist deaths with the least amount of additional sharing of livers and minimizes the distance the organs travel," recommends Dr. Washburn.
Sources: Wiley-Blackwell, AlphaGalileo Foundation.

Pharmaceuticals

FDA Wants To Make It Safer To Split Tablets
The practice of splitting tablets is nothing new. Countless people do so every day to save money or adjust dosages, but how does one know that each half - or portion - contains the needed amount of medication? Just because a tablet is scored - which is industry-speak for visible markings on the tablet coating - is not a guarantee that patients will get what they need.

Bioethics commission condemns Guatamalan syphilis research as unethical
Posted: 2011-08-30 14:52
Crossposted from Nature's news blog
Researchers knowingly violated ethical boundaries when they intentionally infected Guatamalan prisoners, mental health patients, and prostitutes with sexually transmitted diseases in a 1940s research project, a presidential commission concluded yesterday.
When the harrowing experiments came to light (see 'A shocking discovery'), President Barack Obama charged the President’s Commission for the Study of Bioethical Issues with investigating the matter. After picking through 125,000 pages of historical documents, the committee determined that the experiments were unethical even by the prevailing norms of the era, and that those who conducted the research actively sought to keep experiments out of the public eye.
It was also no accident that the research was performed in Guatemala, argued Amy Gutmann, chairwoman of the commission and president of the University of Pennsylvania. “Some of the people who were involved in this experiment explicitly said, ‘We could not do this in our own country’,” she said. “It was a foreign population that was seen as ethnically, racially, nationally different.”
“The only way you could continue doing this is to think of what you were working on as material as opposed to human subjects,” Gutmann added.
Continue reading on Nature's news blog.

FYI

New Tests for “Legal Marijuana,” “Bath Salts” and Other Emerging Designer Drugs
Released: 8/25/2011 1:00 PM EDT
Embargo expired: 8/30/2011 6:00 PM EDT
Source: American Chemical Society (ACS)
Michael Bernstein mailto:Bernsteinbernstein@acs.org 303-228-8532 (Aug. 25-Sept. 1)202-872-6042 (Before Aug. 25)Michael Woodsmailto:m_woods@acs.org?subject=Newswise 303-228-8532 (Aug. 25-Sept. 1)202-872-6293 (Before Aug. 25)

Description
Scientists today reported development of much needed new tests to help cope with a wave of deaths, emergency room visits and other problems from a new genre of designer drugs sold legally in stores and online that mimic the effects of cocaine, ecstasy and marijuana.

New tests will help law enforcement officials cope with a new genre of “bath salts” and other designer drugs that mimic the effects of cocaine, ecstasy and marijuana—a legal “high” in many states.


EMBARGOED FOR RELEASE: Tuesday, August 30, 6 p.m. Eastern Time
Note to journalists: Please report that this research was presented at a meeting of the American Chemical Society

Newswise — DENVER, Aug. 30, 2011 — Scientists today reported development of much needed new tests to help cope with a wave of deaths, emergency room visits and other problems from a new genre of designer drugs sold legally in stores and online that mimic the effects of cocaine, ecstasy and marijuana. They spoke at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), being held here this week.

The reports, among more than 7,500 on the ACS agenda, focus on drugs sold as “bath salts,” “plant food,” “incense” and other products with colorful names, such as “Ivory Wave,” “Red Dove” and “legal marijuana.” They provide users with a high, but many have not yet been made illegal and are undetectable with current drug tests. In one presentation on these “legal highs,” a United Kingdom researcher reported a new method to trace the source of the substances in “bath salts.” In the other, a U.S. researcher discussed the challenges facing law enforcement and policy makers in regulating synthetic versions of marijuana.

Oliver Sutcliffe, Ph.D., and his collaborators reported the successful use of a method called isotope ratio mass spectrometry (IRMS) to determine who is making bath salts — drugs that can cause euphoria, paranoia, anxiety and hallucinations when snorted, smoked or injected — and which chemical companies supplied the raw materials. He and his co-workers are based at the University of Strathclyde and the James Hutton Institute in the U.K.
“With the new method, we could work backwards and trace the substances back to the starting materials,” said Sutcliffe. IRMS measures the relative amounts of an element’s different forms, or isotopic ratio. “This method was successful because the isotopic ratio of the starting material is transferred like a fingerprint through the synthesis,” he explained.

“Bath salts” first garnered major media attention in the U.K. in early 2010, and then became a problem in the U.S. These products are not in the supermarket soap aisle — they are sold on the Internet, on the street and in stores that sell drug paraphernalia. They are sold in small individual bags for as low as $20 each for the real purpose of providing a cheap, legal high.
The powders often contain mephedrone, which is a synthetic compound, structurally related to methcathinone, which is found in Khat — a plant that is illegal in many countries, including the U.K. and the U.S. Usually, that would mean that these compounds (and derivatives thereof) would be illegal in those countries too, but because the bath salts are labeled “not for human consumption,” they get around this restriction and other legislation governing the supply of medicines for human use. However, Florida and Louisiana — two hotspots of bath salts abuse — specifically banned the substances. U.K. officials banned the import of bath salts, which may lead some in the drug trade to set up clandestine labs on U.K. soil, said Sutcliffe. The new method provides law enforcement with a tool to track down these bath salts manufacturers.
In previous work, Sutcliffe developed the first pure reference standard for mephedrone, as well as the first reliable liquid chromatography test for the substance, which could be easily run in a typical law enforcement lab. The team is also developing a color-change test kit for mephedrone, which he estimates may be available by the end of the year.

In another presentation, Robert Lantz, Ph.D., from the Rocky Mountain Instrumental Laboratories, described another high that is legal in most of the U.S. — synthetic cannabinoids marketed as incense, a spice product or “legal marijuana” that give a high similar to marijuana without showing up in conventional drug tests.

“We can detect synthetic cannabinoids with modern analytical chemistry techniques, such as liquid or gas chromatography coupled to mass spectrometry, but these assays are too expensive for the 5,000-10,000 urine samples that most drug testing labs receive each day,” said Lantz. Most labs screen for drugs with less expensive antibody assays, but because the structures of these substances are so dissimilar, different antibodies would likely be required for many of them, driving up the cost of a more comprehensive test.

Synthetic cannabinoid abuse rose sharply in 2010, according to U.S. poison control centers, up to 2,863 compared to only 14 in 2009. About 200 synthetic cannabinoids exist, but the U.S. Drug Enforcement Agency (DEA) banned only five of those. A handful of states, such as Washington, Georgia and Colorado, banned five of them, but they are not always the same five that the DEA banned. “The states banned several specific compounds without a particular basis for their choices,” Lantz pointed out.

Colorado recently passed a law banning any substance that binds to a cannabinoid receptor in the human body. “The bill was well-intentioned, but technically, the new law not only covers synthetic cannabinoids, but also endocannabinoids, which are naturally occurring substances that the human body produces to regulate many normal processes,” said Lantz.
The American Chemical Society is a non-profit organization chartered by the U.S. Congress. With more than 163,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

# # #

Abstract (Dr. Sutcliffe):
The increase in the global abuse of synthetic cathinones has given rise to significant legal and analytical challenges in their identification and quantification - thus rapid methods of testing (especially in the field) are urgently required. This paper presents synthesis; characterisation; validated presumptive and quantitative methods for these substances (both in pure and adulterated samples) and a rapid, novel NMR screening technique for street samples containing components which cannot normally be detected using standard chromatographic methods.

Abstract (Dr. Lantz):
There is no end to human ingenuity. Unfortunately, this phrase even provides to be true when it comes to methods and means of getting high. Synthetic Cannabinoids, such as JWH-018 which is only one of many such substances (which is currently marketed as K2), and other substances such as Methylone (MDPV) and Mephedrone (which is currently marketed as “Bath Salts” or “Plant Food” respectively) present unique analytical chemistry challenges from a chromatographic point-of-view. Related challenges in terms of quantitation of these substances still exist. In the rush to make illegal and prosecute the possession and use of these substances, errors related the qualitative and quantitative reporting of these compounds can occur. This presentation will examine these challenges that exist and what lies ahead.
Permalink to this article

Hepatitis C-TMC435 ;MedivirAB Completed Enrollment of Three Global Phase 3 Trials

08/31/2011 07:20 am

TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).

Medivir AB : Completed Enrollment of Three Global Phase 3 Trials for TMC435 in Chronic Hepatitis C Genotype-1 Infected Patients

Press release
31-Aug-11 Huddinge, Sweden – MedivirAB (OMX: MVIR) is an emerging researchbased specialty pharmaceutical company focused on infectious diseases.

Medivir today announced that its investigational protease inhibitor TMC435, developed by Tibotec Pharmaceuticals, has successfully completed enrollment of three ongoing global phase 3 trials and further reports that all patients are now on TMC435 or active control treatment. The trials are QUEST 1 and QUEST 2, in treatment naive patients, and PROMISE in the treatment experienced relapser patient population. In all three trials, the duration of total treatment is response guided and patients in the TMC435 arms are eligible to stop all treatment at week 24 if predefined response-guided criteria are met.

Medivir recently announced that TMC435 had received “Fast Track” designation by the U.S. Food and Drug Administration (“FDA”) for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435’s potential to address unmet medical needs in the treatment of chronic HCV infection.

In parallel to these trials, phase 3 studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, have also completed enrollment.

Global Phase 3 Program in brief:
· TMC435-C208 or QUEST-1 includes approximately 375 treatment-naïve patients
· TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve patients
· TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment

Bertil Samuelsson, Chief Scientific Advisor at Medivir, comments - "We are extremely excited to have completed the enrollment and patient dosing in three large global phase 3 trials. It is a monumental milestone step for Medivir as a company and for TMC435 progress towards market registration. The completed enrollment of phase 3 studies for TMC435 in Japan represents another key project milestone achievement.”

For more information about Medivir, please contact:
Medivir (www.medivir.com (http://www.medivir.com/)):
M:Communications:Peter Laing / Amber Bielecka Medivir@mcomgroup.com (Medivir@mcomgroup.com) +44(0)20 7920 2330
USA: Roland Tomforde +1 212-232-2356

About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.

TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).

In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated and in July 2011 Medivir confirmed the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435 and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor.

Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.

For additional information from these studies, please see www.medivir.com (http://www.medivir.com/) and www.clinicaltrials.gov

About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec

Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir’s first product, the unique cold sore product Xerese®/Xerclear® was launched on the US market in February 2011. Xerese®/Xerclear®, which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.com (http://www.medivir.com/)

FDA Request That H&P Recall Povidone Iodine Prep Solutions W-other Multiple brands affected

  • Tuesday, August 30, 2011
  • Posted by HCV New Drugs
  • File Under

Earlier this year the HCV community remembers all too well the recall for prep pads manufactured by Triads parent company H&P. The prep pads were packaged with pegasys in the U.S . and Pegintron outside the U.S. It was reported that the pads from H&P were potentially contaminated with a rare bacteria, Bacillus cereus.

Click Here To Review All Previous Updates

Released Aug 27 2011
--------------------

H & P Industries Povidone Iodine Swabsticks, Prep Solutions, Scrub Solutions, and Prep Gel: Recall - Inadequate Microbial Testing

Multiple brands affected - listed below

[Posted 08/27/2011]

AUDIENCE: Pharmacy, Consumer, Risk Manager

ISSUE: H & P Industries and FDA notified health professionals and the public of a recall of all lots (lots beginning with 8J-8M, 9A-9M, 0A-0M, 1A-1C) of Povidone Iodine Swabsticks, Prep Solutions, Scrub Solutions, and Prep Gel. H & P Industries, Inc. manufactured these Povidone Iodine products without having in place a system for microbial testing at the time of release, without having a system for testing of incoming components, and without having procedures designed and established to prevent objectionable microorganisms in these drug products. Patients undergoing medical and surgical procedures, including those who are immunocompromised, have a high risk of infection from antiseptic surgical preparations that have been prepared, packaged, or held under insanitary conditions. This recall has been initiated at the request of FDA.

BACKGROUND: Povidone Iodine Swabsticks, Povidone Iodine Prep Solutions, Povidone Iodine Scrub Solutions, and Povidone Iodine Prep Gel are labeled as an antiseptic for preparation of the skin prior to surgery, and are used to prevent infection in minor cuts, scrapes and burns. The Povidone Iodine Scrub solutions are labeled also for use as a surgical hand scrub for health care professionals. The Povidone Iodine products were distributed nationwide to healthcare customers. The swabsticks are packaged in individual packets of 1 or 3 swabs and the Prep Solution, Scrub Solution and Prep Gel are sold in bottles.

RECOMMENDATION: Specific customers distributing the product and selling it at the wholesale and hospital level are being notified by e-mail with instructions on how to return the product. Consumers that have any of these types of products in their possession should not use the product and should return it to the place it was purchased.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm1
Download form 2 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Swabsticks
Amerinet
Cardinal Health
Nova Plus
PSS Select - Select Medical Products
Triad
Triad Plus

Prep Solutions
American Fare - Smart Sense, Kmart
Amerinet
Equaline, Albertson's
Fred's
Good Neighbor - Good Neighbor Pharmacy, Amerisource Bergen
Good Sense - Geiss, Destin & Dunn, Inc.
Leader - Cardinal Health
Major
Meijer
Nova Plus
Premiere Value - Chain Drug Consortium
PSS Select - Select Medical Products. PSS World Medical
Triad - Triadine
Triad Plus
Walgreens
Winn Dixie - Medic

Gel
Triad Plus

Scrub
Amerinet
Nova Plus
Triad
Triad Plus

08/24/2011 - Press Release 3 - H&P Industries, Inc

H&P Industries, Inc. Issues a Voluntary Recall of All Lots of Povidone Iodine Swabsticks, Povidone Iodine Prep Solutions, Povidone Iodine Scrub Solutions, and Povidone Iodine Prep Gel

Contact:Consumer:262-538-2907
Returns:mailto:recall.coordinator@handpindustries.com%20?subject=

FOR IMMEDIATE RELEASE -
August 24, 2011 -

H&P industries, Inc., a manufacturer of over-the-counter drug products has initiated a voluntary recall of ALL LOTS (Lots beginning with 8J-8M, 9A-9M, 0A-0M, 1A-1C)of Povidone Iodine Swabsticks, Povidone Iodine Prep Solutions, Povidone Iodine Scrub Solutions, and Povidone Iodine Prep Gel manufactured by H&P Industries, Inc.

This recall has been initiated at the request of the FDA. H & P Industries, Inc. manufactured these Povidone Iodine products without having in place a system for microbial testing at the time of release, without having a system for testing of incoming components, and without having procedures designed and established to prevent objectionable microorganisms in these drug products. Although H&P Industries, Inc.’s investigation and extensive testing did not find contamination, and the products met H&P Industries, Inc., finished goods specifications, H&P Industries, Inc. is voluntarily recalling all Povidone Iodine Products due to and in accordance with the Consent Decree of Condemnation, Forfeiture, and Permanent Injunction entered in the Eastern District of Wisconsin (Civil No. 2:11-cv-00319-AEG) on June 13, 2011. Povidone Iodine Swabsticks, Povidone Iodine Prep Solutions, Povidone Iodine Scrub Solutions, and Povidone Iodine Prep Gel are labeled as an antiseptic for preparation of the skin prior to surgery, and are used to prevent infection in minor cuts, scrapes and burns. The Povidone Iodine Scrub solutions are labeled also for use as a surgical hand scrub for health care professionals.

Patients undergoing medical and surgical procedures, including those who are immunocompromised, have a high risk of infection from antiseptic surgical preparations that have been prepared, packaged, or held under insanitary conditions whereby they may have been rendered injurious to health. H&P Industries, Inc. has not ever received reports of adverse events or contamination attributed to these Povidone Iodine products. The Povidone Iodine products were distributed nationwide to healthcare customers. The swabsticks are packaged in individual packets of 1 or 3 swabs and the Prep Solution, Scrub Solution and Prep Gel are sold in bottles. These products were distributed in the United States. Specific customers distributing the product and selling it at the wholesale and hospital level are being notified by e-mail with instructions on how to return the product. Consumers that have any of these types of products in their possession should not use the product and should return it to the place it was purchased.

Consumers with questions can call H&P Industries, Inc. at 262-538-2907 Monday through Friday between the hours of 8:30 A.M. and 4:00 P.M. Central Time.

CUSTOMERS WHO DIRECTLY PURCHASED PRODUCT FROM H&P SHOULD NOT RETURN THE PRODUCT ON YOUR OWN.

Email H&P Industries, Inc. at mailto:recall.coordinator@handpindustries.com?subject= to make all return arrangements. Returns will be processed once recall acknowledgements and/or a notice of destruction have been received. Adverse reactions or quality problems experienced with the use of these products may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

Online:www.fda.gov/medwatch/report.htm1 Regular Mail: use postage-paid, pre-addressed Form FDA 3500 available at: www.fda.gov/MedWatch/getforms.htm2.
Mail to address on the pre-addressed form. Fax: 1-800-FDA-0178 This recall is being conducted with the knowledge of the U.S. Food & Drug Administration.

Mythbusters: Learn the Truth about Food Safety in Your Home


Mythbusters: Learn the Truth about Food Safety in Your Home
By Howard Seltzer, National Education Advisor, Center for Food Safety and Applied Nutrition, FDA

It’s September, so it’s time for us to bust some myths.
Beginning in the mid-90’s, National Food Safety Education Month has focused public attention on safe food handling and preparation. Since 2009, the U.S. Department of Agriculture, the Food and Drug Administration, and the Centers for Disease Control and Prevention, in cooperation with the non-profit Partnership for Food Safety Education, have marked the occasion by exposing myths about food safety that somehow keep cropping up.

Food safety myths may not sound very serious. But they may cause food handling mistakes that can lead to food poisoning, severe illness, and even death. So it’s important to get the facts straight.

Here are the myths — and the facts — for 2011:
Myth: I eat a vegetarian diet, so I don't have to worry about food poisoning.
Fact: Fruits and vegetables are an important part of a healthy diet. But justlike other foods they carry a risk of foodborne illness. Always rinse produce under running tap water, including fruits and vegetables with skins and rinds that are not eaten. Never use detergent or bleach to wash fresh fruits or vegetables as these products are not intended for consumption. Packaged fruits and vegetables labeled “ready-to-eat” or “washed” don’t need to be re-washed. Learn more tips at: http://www.foodsafety.gov/keep/types/fruits/index.html.

Myth: Freezing foods kills harmful bacteria that can cause food poisoning (also called foodborne illness).
Fact: Bacteria can survive freezing temperatures. Freezing food is not a method for making foods safe to eat. When food is thawed, bacteria can still be present and may begin to multiply. Cooking food to the proper internal temperature is the only way to kill harmful bacteria. Use a thermometer to measure the internal temperature of cooked foods. See the chart at: http://www.foodsafety.gov/keep/charts/mintemp.html.

Myth: Locally grown, organic foods will never give me food poisoning.
Fact: Any food from any source can become unsafe if it is not handled and stored properly. Consumers in their homes can take action to keep themselves and their families safe. That is why it is important to reduce your risk of food poisoning by practicing the four steps to food safety: Clean, Separate, Cook, and Chill. Learn more about these steps at: http://www.foodsafety.gov/keep/basics/index.html.

Myth: Plastic or glass cutting boards don't hold harmful bacteria on their surfaces like wooden cutting boards do.
Fact: Regardless of the type of cutting board you use, it should be washed and sanitized after each use. Solid plastic, tempered glass, sealed granite, and hardwood cutting boards are dishwasher safe. However, wood laminates don’t hold up well in the dishwasher. Once cutting boards of any type become excessively worn or develop hard-to-clean grooves, they should be discarded.

Mythbusters of past years can be found at
http://www.foodsafety.gov/keep/basics/myths/.

Facebook App; Watching Viruses "Friend" a Network

  • Posted by HCV New Drugs
  • File Under

Watching Viruses "Friend" a Network
Tuesday, August 30, 2011

TAU develops a Facebook application to track the path of infection
From SARS to swine flu, virus outbreaks can be unpredictable — and devastating. But now a new application through the ubiquitous social networking site Facebook, developed in a Tel Aviv University lab, is poised to serve as a better indicator of how infections spread among populations.

Dr. Gal Almogy and Prof. Nir Ben-Tal of the Department of Biochemistry and Molecular Biology at TAU's George S. Wise Faculty of Life Sciences have developed a Facebook application called PiggyDemic, which allows users to "infect" their friends with a simulated virus or become infected themselves. The resulting patterns will allow researchers to gather information on how a virus mutates, spreads through human interaction, and the number of people it infects. Their research was recently presented at the annual retreat of the Safra Bioinformatics Program.

Programming a social disease
Dr. Gal Almogy
Currently, scientists use mathematical algorithms to determine which virus will spread and how, but this method has some flaws. It assumes that a virus has equal distribution across populations, but that is simply not the case, the researchers say. Patterns of social interaction must also be taken into account. "HIV is concentrated in Africa; certain types of flu are widespread in North America and Asia," explains Dr. Almogy. "Adding the element of human interaction, and looking at the social networks we belong to, is critical for investigating viral interaction."

Facebook, notes Dr. Almogy, is an ideal tool for such an undertaking. The social networking site's digital interactions simulate in-person interactions. Viral infections like the flu are a social phenomena, he explains.

Once added to a user's Facebook account, PiggyDemic follows the user's newsfeed to determine the people they interact with. Users are deemed "susceptible," "immune" or "infected" with various simulated viruses, and can pass them on to their online contacts. Researchers then follow these interactions using network visualization software, and watch the links between users as the "viruses" are passed on.
According to Dr. Almogy, accurate modeling of viral dynamics is critical for developing public health policy. Issues such as the use of vaccinations, medications, quarantine and anti-viral procedures will be better informed if we are able to predict more accurately the course of infection.

Taking your vitamin C
Prof. Nir Ben-Tal
More than a research tool, PiggyDemic is also a game (users try to infect as many of their friends as possible), a teaching tool (users make choices that help them live a healthy life), and potentially a method for high-resolution, real-time tracking of virus outbreaks.
"People who have this software can report if they are actually ill," says Dr. Almogy. "If we know who their friends are and the sequence of the infecting virus, we can figure out which virus they have and how it passes from one person to another." If the network is large enough, he explains, they might be able to post warnings of possible outbreaks to Facebook networks, letting people know when it's time for a hefty dose of vitamin C.
The application has already provided a signficant finding, the researchers report. Flu's peak period, winter, is usually attributed to environmental conditions. But the researchers' findings suggest there are other forces at work.

PiggyDemic's viruses are not explicitly programmed to have a seasonal pattern, and yet like the real-life flu, they also display recurrent peaks of infection. Though researchers are not yet certain what drives these periodic peaks in the PiggyDemic eco-system, they indicate that a simple viral strategy superimposed on the basic structure of human society has a strong tendency to display periodic bursts of viral activity regardless of environmental conditions. "The flu doesn't maintain itself at a steady rate of infection," explains Dr. Almogy. "Yearly peaks of infection may serve instead as 'seeding periods,' similar to the 'blooming' process we see in flowering plants."

To download the application to a Facebook account, go to http://apps.facebook.com/piggydemic/.

Hepatitis C; Response To Treatment Geno 3-fibrosis but not race encourages relapse

European Journal of Gastroenterology & Hepatology:
September 2011 - Volume 23 - Issue 9 - p 747–753
doi: 10.1097/MEG.0b013e3283488aba

Original Articles: Hepatitis

Response to antiviral therapy in patients with genotype 3 chronic hepatitis C: fibrosis but not race encourages relapse

Shoeb, Daniaa; Rowe, Ian A.b; Freshwater, Dennisb; Mutimer, Davidb; Brown, Ashleyc; Moreea, Sullemand; Sood, Ruchitd; Marley, Richarda; Sabin, Caroline A.e; Foster, Graham R.a

Abstract
Background and aims:
We completed a retrospective analysis of patients with genotype 3 hepatitis C virus (HCV) undergoing therapy in four UK centres with large populations of patients from the Indian subcontinent.

Materials and methods:
Notes on all patients treated with pegylated interferon and ribavirin were reviewed and factors that influenced the response were examined.

Results:
Six hundred and four patients with genotype 3 HCV were studied, of whom 299 were Asians. Median age was 43 years, 65% were men and 24% had cirrhosis. Overall, 457 (76%) patients achieved sustained virological response (SVR). By multivariable analysis it was found that ethnicity was not associated with an impaired response but age, cirrhosis and diabetes were significantly associated with a reduced SVR, the likelihood of a response was reduced by 25% per 10-year increment in age, by 59% among individuals with cirrhosis and by 62% among individuals with diabetes mellitus. Most patients who did not achieve an SVR relapsed (15%) rather than failing to achieve an end of treatment response.

Conclusion:
The response to antiviral therapy in genotype 3 HCV is not affected by South Asian (vs. Caucasian) ethnicity, but age, cirrhosis and diabetes reduce the response. Treatment failure most often is due to relapse.

Source

Hepatitis; FDA Draft Guidance Document May Limit Patient Access to Tests

  • Posted by HCV New Drugs
  • File Under

FDA Draft Guidance Document May Limit Patient Access to Tests
Released: 8/30/2011 1:30 PM EDT
Source: Association for Molecular Pathology

“Some products used for laboratory tests are available only as research or investigational use only products,” explained AMP Professional Relations Chair Dr. Elaine Lyon. “If this guidance were to be finalized, we’re concerned that patients won’t be able to access tests such as those for Hepatitis C genotyping, newborn screening and HLA testing,” added Dr. Lyon.

Newswise — WASHINGTON, DC, August 30, 2011—
The Association for Molecular Pathology (AMP) submitted comments to the US Food and Drug Administration on the draft guidance document titled, “Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions.” AMP is very concerned that this guidance could compromise the quality of patient care by severely reducing the availability of certain reagents and laboratory developed testing services that have become the standard of care for many diseases or conditions. Specifically, if enforced in its broadest sense without sufficient accommodations for low test volume or sufficient time for manufacturers to achieve submission compliance, the draft guidance document could result in reduced availability of testing services would limit a healthcare provider’s ability to manage patient care, and ultimately limit patient access to new or improved molecular tests.

“Some products used for laboratory tests are available only as research or investigational use only products,” explained AMP Professional Relations Chair Dr. Elaine Lyon. “If this guidance were to be finalized, we’re concerned that patients won’t be able to access tests such as those for Hepatitis C genotyping, newborn screening and HLA testing,” added Dr. Lyon.

AMP supports FDA clearance and approval of research use only (RUO) and investigational use only (IUO) products, especially test kits and test systems. However, to prevent disruption of patient care, accommodations should be made to ensure continued patient access to critical tests as manufacturers come into compliance and/or instances where low test volume would deter a manufacturer from submitting an application to the FDA for that product.

“While AMP appreciates the FDA concern over the use of RUO and IUO products in laboratory developed tests, the Association questions the underlying assumption that the guidance will encourage most manufacturers to seek clearance and approval for their RUO and IUO products,” said Dr. Lyon. AMP members fear that instead of seeking FDA review, some manufacturers will choose to withdraw RUOs from the clinical market. This has already occurred for many analytes, from blood-borne pathogens to sexually transmitted diseases. This would then create a shortage of supplies to develop laboratory tests, resulting in a scarcity of tests, and ultimately, barriers for patients’ access to medically necessary tests.
Dr. Lyon added, “Today we are asking the FDA to consider the downstream implications of the guidance on the supplies and materials for laboratory testing, and allow for circumstances where clinical laboratories can develop tests using RUO and IUO products when no other products are available.”

AMP’s recommendations include:1. To avoid the disruption of patient care, carefully consider enforcement discretion or alternative regulatory pathways to address circumstances where no FDA cleared/approved products are available, particularly for those products with limited sales volume.2. Direct enforcement requirements for 510(k) or PMA submissions toward test kits and test systems. 3. Create a consistent and clear pathway to encourage and facilitate ASR, 510(k) or PMA applications for RUO and IUO products, with a reasonable compliance timeline. The pathway must include flexibility to be responsive to rapidly evolving areas. 4. Accommodations should be made to enable certain reagents such as primer or probe mixes to be sold as ASRs. Alternatively, another regulatory pathway could be designed for products that are too complex to qualify as ASRs but are not full test kits or test systems. 5. Clearly state the scope of the guidance. Clarify which products currently labeled as RUOs and IUOs the guidance covers, e.g., test kits, instruments, software, and reagents.

About AMPThe Association for Molecular Pathology (AMP) is an international medical professional association dedicated to the advancement, practice, and science of clinical molecular laboratory medicine and translational research based on the applications of molecular biology, genetics, and genomics. For more information, please visit www.amp.org.

Video; Victrelis, and Incivek-2 new drugs to fight Hepatitis C





Ali Gorman, R.N. More: Bio, Facebook, Twitter, News Team
August 30, 2011 (WPVI) -- The Food and Drug Administration recently approved two new drugs that could be revolutionary. They will dramatically raise the cure rate for a disease that ot too long ago didn't have a treatment.


When Kelly Ann Hester learned she had Hepatitis C in 1993, the disease didn't even have a formal name and doctors didn't give the young mother much of a future...Continue reading..

Hepatitis C-Needlestick Injuries – A Nurse's Story-Video

Staff Education Tool: 'Needlestick Injuries – A Nurse's Story' Video





The National Institute for Occupational Safety and Health, a part of the CDC, offers a free, nine-minute video featuring an interview with Diane Mawyer, a nurse whose life was changed by a sharps injury that infected her with hepatitis C.

Hepatitis C Monday News Ticker; Paediatric HCV, Two New Drugs for Chronic Hepatitis C and More

New On The Blog;
Canada-Victrelis;New Hep C drug priced out of reach of most patients
Maternal hepatitis B and hepatitis C carrier status influences perinatal outcomes
Fatigue In HCV Infection: A Review (1989-2011)

In The News

Clinic: Patients Might Have Been Exposed To Hepatitis, HIV
Victims Potentially Exposed Between 2006 To 2011
Updated: 1:50 pm CDT August 29, 2011
MADISON, Wis. -- Dean Clinic officials said on Monday that a former employee might have exposed some patients to blood-borne diseases like hepatitis and HIV during the last five years.
Clinic officials released a news release on Monday saying that they've informed state and local health officials about the results of their internal review. They said that the employee conducted "inappropriate use of insulin demonstration pens and finger stick devices" during patient visits between 2006 and 2011. They're now contacting 2,345 patients to check if they were exposed to hepatitis B, hepatitis C and HIV.

Officials said that they will either call or send letters and have prepared to answer patients' questions. They said that they conduct the necessary testing and coordinate "follow-up care and support patients' needs."

Dean leaders said that they're committed to helping those affected.
"Dean Clinic is committed to supporting our patients. There is nothing more important to us than the health, well-being and safety of the people we serve," said Dr. Craig Samitt, president and CEO of Dean Clinic, in the news release. "Our goal is to ensure that those who may have been affected by the inappropriate use are promptly informed, tested and supported."
As a result of these incidents, officials said that they're "reeducating patient care staff on the proper use of these types of devices, enhancing our auditing and monitoring procedures related to these devices and improving our process for routinely observing the clinical practices of our staff."
Stay tuned to WISC-TV and Channel 3000 for continuing coverage.

HIV Donor's Organs Transplanted Into Patients
UK, Monday August 29, 2011
A hospital in Taiwan has apologised after organs from an HIV positive donor were transplanted into five patients in a case described as "appalling negligence".
The five are now being treated with anti-viral drugs but experts say it is very likely they will contract HIV.

And their treatment will be further complicated due to the fact they must take medication to stop their new organs being rejected.
There are also concerns among the medics who performed the operations that they may have also contracted HIV.

The family of the 37-year-old donor, surnamed Chiu, chose to donate his organs after he fell to his death in northern Hsinchu city last week.
But the relatives said they were not aware that he was an HIV carrier.
Chiu went into a coma on August 24 and his liver, lungs two kidneys and heart were transplanted to five patients on the same day.

Four of the transplants took place at the National Taiwan University Hospital (NTUH) in Taipei, while the heart operation was carried out at another hospital.
Continue reading..

Hepatitis C Drug
Written by Kristi Runyon
Monday, 29 August 2011 10:47
Hepatitis C is a potentially curable form of hepatitis and some recent advances have improved those odds. Learn more about the newest treatment that can rid the body of this chronic infection.

Hepatitis C Hepatitis C (HCV) is an inflammatory disease that affects the liver. It’s caused by infection with the hepatitis C virus. Most people don’t have any symptoms until significant liver damage has occurred. By then, patients may develop jaundice (yellowish coloring of the skin and whites of the eyes), swelling in the stomach or ankles, fatigue, easy bruising, slower blood clotting time, fever, loss of appetite, diarrhea and dark colored urine.

According to the Centers for Disease Control and Prevention, about 17,000 people become infected with HCV each year. Many of those who are newly diagnosed were actually infected 30 to 40 years ago, but didn’t know it because the virus generally doesn’t cause any symptoms for a long time. Some risk factors include: being born to a mother with HCV, having received a blood transfusion or organ transplant before July 1992, having more than one sex partner, using illegal drugs, getting a tattoo with contaminated needles or accidental stick with a needle used on a person with HCV.

HCV is very difficult for the body to clear and about 75 to 85 percent of patients develop a chronic infection. Currently, 3.2 million Americans are believed to have chronic HCV. Up to 20 percent of them will develop liver cirrhosis within 30 years. Nearly 5 percent will die from either liver cirrhosis or liver cancer.

Treating HCV Doctors generally only treat HCV when the disease become chronic. The standard treatment is a combination of pegylated interferon alfa (PEG, or peginterferon) and ribavirin (RBV). PEG is given by weekly injection. RBV is an oral medication taken daily.
Researchers say the two-drug combination successfully cures HCV in only 40 percent of cases. So better treatments are being investigated.

Recently, the FDA approved two new drugs for HCV – boceprevir and telaprevir. Both drugs are in a class of medications, called protease inhibitors, which inhibit replication of the HCV virus. However, when used alone, the virus quickly develops a resistance to the drugs. So doctors are now adding a protease inhibitor to the standard treatment, allowing them to attack the HCV virus with a triple punch. David Bernstein, M.D., Hepatologist with North Shore University Hospital, Manhasset, NY, says the total treatment time is 6 or 12 months, depending upon the patient’s response to the therapy. All three medications are given for the first three months, then the protease inhibitor is discontinued. Patients continue to take the other two medications as directed for the remaining treatment time.

There are six different genotypes of HCV. The protease inhibitors only work against type 1. However, that is the most common type in the U.S. and it is the strain that is most resistant to treatment. Bernstein cautions the protease inhibitors still don’t work for everyone. However, cure rates with the triple therapy are up to 79 percent.
Research compiled and edited by Barbara J. Fister

AUDIENCE INQUIRY
For information about the new drugs: boceprevir - http://victrelis.com/boceprevir/victrelis/consumer/index.jsp?WT.srch=1&WT.mc_id=VI00J&gclid=CPGtwojBwKoCFdZ25Qod4EZ0jg
telaprevir - https://www.incivek.com/?cid=20657&gclid=CMWogN3AwKoCFQbe4AodNGkJDg

For general information on hepatitis C: American Liver Foundation, http://www.liverfoundation.org/ Centers for Disease Control and Prevention, http://www.cdc.gov/hepatitis Hepatitis Foundation International, http://www.hepfi.org/ National Institute of Diabetes and Digestive and Kidney Diseases, http://www.niddk.nih.gov/

Portal vein thrombosis influences outcomes for pediatric liver transplant candidates in the USA
The latest issue of Liver Transplantation evaluates portal vein thrombosis and outcomes for pediatric liver transplant candidates and recipients in the United States.
The effect of occlusive portal vein thrombosis on the mortality of pediatric liver transplant candidates and recipients is poorly defined.

Dr Seth Waits and colleagues from Michigan, USA studied the relationship between portal vein thrombosis and waiting-list and posttransplant survival rates with data from the Scientific Registry of Transplant Recipients.
In all, 5087 liver transplant candidates and 3630 liver transplant recipients were evaluated during the period.

Portal vein thrombosis patients had a lower survival rate in the posttransplant period
Liver Transplantation


The research team found portal vein thrombosis in 1% of the liver transplant candidates, and in 4% of the liver transplant recipients.
Portal vein thrombosis was not associated with increased wait-list mortality.
Conversely, portal vein thrombosis patients had a significantly lower unadjusted survival rate in the posttransplant period.

The team observed that portal vein thrombosis was independently associated with increased posttransplant mortality in multivariate models.

Dr Waits' team concludes, "The presence of portal vein thrombosis in pediatric liver candidates was not associated with increased wait-list mortality but was clearly associated with posttransplant mortality, especially in the immediate postoperative period."
Liver Transplant 2011: 17(9): 1066–1072
29 August 2011

Woman hospitalised by abortion
Lateline - 26/08/2011 A woman is in a critical condition in a Melbourne hospital after a late-term abortion at a clinic previously implicated in a hepatitis C scandal.

From;
AJN, American Journal of Nursing:
September 2011 - Volume 111 - Issue 9 - p 22
doi: 10.1097/01.NAJ.0000405053.00454.26

Drug WatchTwo New Drugs for Chronic Hepatitis C
More From Drug Watch @ AJN
New Drug to Treat HIV Infection
New Drug for Type 2 Diabetes

From Journal of Viral Hepatitis
The Impact of Mode of Acquisition on Biological Markers of Paediatric Hepatitis C Virus Infection
K. England; C. Thorne; H. Harris; M. Ramsay; M.-L. Newell
Authors and Disclosures
Posted: 08/29/2011; J Viral Hepat. 2011;18(8):533-541.
© 2011 Blackwell Publishing

Discussion Only;
The impact of mode of acquisition on biological markers of HCV infection in the largest comparison of vertically and parenterally infected children to date was investigated. A significantly higher mean ALT z-score in vertically vs parenterally infected and a significantly higher mean ALT z-score in children infected before 12 months of age, regardless of mode of acquisition, was found. This latter association did not remain when only parenterally infected children were investigated which may be because of small numbers but may also indicate that the differences between groups are not completely explained by age at infection but may be related more directly to the mode of acquisition of infection itself.

Comparing biological markers of HCV infection in vertically and parenterally infected children is problematic in the light of the often substantial differences in populations in terms of age at infection, age at study entry, treatment profile, likelihood of clearance of viraemia or genotype. In the children from the cohorts studied here, four times as many parenterally than vertically infected children received HCV treatment; this may be because of more severe disease in parenterally infected children because of their age or mode of acquisition, as suggested by the finding here of a higher proportion with two or more markers of disease progression. Alternatively, their older age at diagnosis may make them more eligible for the treatment while vertically infected children, who were followed from birth, will have started on a regime of clinical monitoring without treatment. Although HCV therapy is well adhered to in the paediatric population, the unpleasant side effects and the potential impact on growth make the decision to treat a complex one.[18] There could also be bias in terms of the individual clinic or national treatment policies, especially given the continually evolving nature of information on paediatric HCV treatment and the ongoing debate about when to initiate treatment.[19]

This debate on when to initiate treatment is partly fuelled by knowledge that some children spontaneously clear viraemia without treatment. In this study, there was no effect of mode of acquisition on clearance of viraemia in contrast to some previous studies.[20] However, parenterally infected children in the UK National HCV Register were not followed up from the time of infection and possibly a large number of those who cleared viraemia did so before diagnosis or study entry. Therefore, any estimate of clearance here and elsewhere, likely underestimates the true proportion clearing viraemia in parenterally infected groups. Of note, however, the high clearance rates in parenterally infected groups are reported in this and other studies[9,21,22] which would presumably be even higher if those who cleared viraemia prior to diagnosis could be included. It may therefore be the case that parenterally infected children are more likely to clear the virus than vertically infected children but it is unlikely that this can be substantiated as follow-up from infection in parenterally infected children is rare.

No differences were found in the HCV genotype profiles of vertically and parenterally infected children in contrast to Jara et al. who found genotype 1b more frequently in children with transfusion-acquired HCV and genotype 3 more frequently in vertically infected children from seven European countries.[23] It is possible that this is because of differences in the years at which infection occurred and may reflect changes in the genotype profile of the HCV epidemic in Europe as suggested recently.[24] A higher proportion of children with genotypes other than type 1 achieved a SVR to therapy, as has been reported by other paediatric studies.[24]

Additionally, in univariable logistic regression, children with genotype 1 were more likely to have consistently elevated ALT levels and consistently positive HCV RNA PCR results, although the associations did not reach statistical significance likely because of small numbers. This finding does however support those of Harris et al. who suggested that type 1 infections may be more aggressive than types 2 or 3[25] and those of a previous EPHN study which found that intrauterine vertical transmission was more likely to occur from mothers with genotype 1.[26]

As no differences in the genotype profile of vertically and parenterally infected children were found here, it is unlikely that any differences in biological or clinical markers of HCV infection between groups can be attributed to the possible differences in HCV progression by genotype.
In multivariable logistic regression, no association between consistently raised ALT z-scores and mode of acquisition was found, possibly because of a lack of power, although the odds ratio remained below one, indicating higher ALT z-scores in vertically infected children. ALT levels have been shown to peak in the first 2 years of life in vertically infected children[27–29] and to adjust for this peak and any other differences resulting from age at measurement, ALT z-scores were used. The finding of increased ALT z-scores in vertically infected children adjusted for age is similar to an Australian study in which significantly higher geometric mean ALT levels in 16 vertically vs 15 parenterally infected children in the first 5 years of life were found, again after accounting for the early peak in ALT levels.[20]

Significant positive associations were found between consistently high ALT z-scores and both consistent HCV RNA viraemia and ever having evidence of hepatomegaly. There was also a higher odds of having consistently positive HCV RNA PCRs in children ever having evidence of hepatomegaly but not significantly so. The associations between these three markers of HCV-related disease progression support previous studies indicating that they may define a group of children with evidence of chronic progressive HCV or who are at increased risk of rapid or more severe progression.[2] In this analysis, similar proportions of parenterally and vertically infected children had evidence of two or more of these markers of infection. Similarly, no difference was found in the proportion with two or more markers and age at infection, in either all children or just the parenterally infected group. This lack of association with mode of or age at acquisition may have been because of combining the markers of infection into this summary variable and also the small number (15 children) of parenterally and vertically infected children with evidence of two or more markers of infection.

The prevalence of comorbidities in parenterally infected children is high given the nature of their infection during receipt of medical treatment[30] and this may have been influential in terms of the child's ability to mount an initial or continued immune response to HCV infection. In contrast, vertically infected children, although acquiring infection during immune development may benefit from persistence of maternal antibodies.[20,31] These mechanisms require specific investigation and although evidence from this analysis does not support substantial differences between the vertically and the parenterally infected groups, until they can be further defined it is important that the potential differences between them are recognized in a clinical setting. This study also highlights the growing need for epidemiological data on parenterally infected children and the difficulties in analyzing such data. Recent estimates suggest that 40% of HCV infections worldwide are acquired via unsafe medical injections and a great number of these occur in children. It is therefore vital that knowledge of disease progression in parenterally infected children is accurate and that the differences between vertically and parenterally infected groups are clarified to inform more accurate and individualized clinical management.
Read More;
Abstract and Introduction
Materials and Methods
Results
Discussion
References

In Case You Missed It

TAG Offers New Guide to Clinical Trials for People with Hepatitis C
The Treatment Action Group (TAG) has produced a new booklet for people considering...

Remembering Jack Layton: full of energy and compassion
remember the first time I met Jack in Ottawa. Six of us infected before 1986 and after 1990 with hepatitis C because of tainted blood went to Ottawa during the Paul Martin Liberal government.

Outsourcing Pharmaceuticals

More Than Half Of CRO Sales Are Made Outside The US

Cancer drug shortages getting worse, FDA says
Most of these are generic drugs given by injection and used in hospitals to treat serious conditions such as breast and testicular cancer. These shortages are putting patients at risk and compromising their care, experts say.
"FDA has been monitoring shortages for the last six years, and in 2010 we saw a large spike in shortages, which was a large jump from the year before," said Valerie Jensen, associate director of the Drug Shortage Program in FDA's Center for Drug Evaluation and Research. "That's what we are continuing to see in 2011. We are still seeing these large numbers of injectable drug shortages." Continue reading...

MORE: Drug shortages set to reach record levels

Stem Cells

Links; Recommended: Stem Cell Blogs

Five Scientists Receive Stem Cell Research Grants

SAN JOSE, Calif., Aug. 29, 2011 /PRNewswire/ -- BD Biosciences, a segment of BD (Becton, Dickinson and Company), has announced the latest round of winners of the BD Biosciences Research Grant Program.

"BD Biosciences continues to support promising young U.S. and European scientists at critical junctures of their careers," said Robert Balderas, Vice President of Biological Sciences, BD Biosciences. "No biomedical discovery has shown as much promise, so early in its development, as stem cell research. We are pleased, by funding these researchers, to support efforts to treat and cure serious illnesses."

Michael Choi, M.D., Assistant Professor of Medicine at Harvard Medical School, is investigating the conversion of non-liver cells into functional hepatocytes through a combination of transcription factors and microRNAs. Specifically, he will identify transcription factors and microRNAs that help convert or differentiate fibroblasts, embryonic stem cells or endodermal (early liver precursor) cells into hepatic progenitor cells. The long-term goal is a ready source of cells to repair livers damaged from injury or disease.
Continue reading....

Stem cells: distinguishing hype and hope
With the bewildering amount of news about stem cells, how do we tell the difference between hype and hope?

New research validates clinical importance of leukemia stem cells
Aug 29
Research published today focuses on patients and shows that acute myeloid leukemia (AML) contains rare cells with stem cell properties, called leukemia stem cells (LSC), that are better at predicting clinical outcome than the majority of AML cells, showing for the first time that LSCs are significant not just in experimental models but also in patients. Stem Cell Network of Canadian National Centres of Excellence, Terry Fox Foundation, Ontario Institute for Cancer Research, Canadian Cancer Society Research Institute

In cell culture, like real estate, the neighborhood matters
Ever since scientists first began growing human cells in lab dishes in 1952, they have focused on improving the chemical soup that feeds the cells and helps regulate their growth. But surfaces also matter, says Laura Kiessling, a professor of chemistry at the University of Wisconsin-Madison.

Healthy You

It's official -- chocolate linked to heart health
High levels of chocolate consumption might be associated with a one third reduction in the risk of developing heart disease, finds a study published on bmj.com today.
The findings confirm results of existing studies that generally agree on a potential beneficial link between chocolate consumption and heart health. However, the authors stress that further studies are needed to test whether chocolate actually causes this reduction or if it can be explained by some other unmeasured (confounding) factor.

The findings will be presented at the European Society of Cardiology Congress in Paris at 10:10 hrs (Paris time) / 09:10 hrs (UK time) on Monday 29 August 2011.
The World Health Organisation predicts that by 2030, nearly 23.6 million people will die from heart disease. However, lifestyle and diet are key factors in preventing heart disease, says the paper.

A number of recent studies have shown that eating chocolate has a positive influence on human health due to its antioxidant and anti-inflammatory properties. This includes reducing blood pressure and improving insulin sensitivity (a stage in the development of diabetes).
However, the evidence about how eating chocolate affects your heart still remains unclear. So, Dr Oscar Franco and colleagues from the University of Cambridge carried out a large scale review of the existing evidence to evaluate the effects of eating chocolate on cardiovascular events like heart attack and stroke.

They analysed the results of seven studies, involving over 100,000 participants with and without existing heart disease. For each study, they compared the group with the highest chocolate consumption against the group with the lowest consumption. Differences in study design and quality were also taken into account to minimise bias.

Five studies reported a beneficial link between higher levels of chocolate consumption and the risk of cardiovascular events. They found that the "highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease and a 29% reduction in stroke compared with lowest levels." No significant reduction was found in relation to heart failure.
The studies did not differentiate between dark or milk chocolate and included consumption of chocolate bars, drinks, biscuits and desserts.

The authors say the findings need to be interpreted with caution, in particular because commercially available chocolate is very calorific (around 500 calories for every 100 grams) and eating too much of it could lead to weight gain, risk of diabetes and heart disease.
However, they conclude that given the health benefits of eating chocolate, initiatives to reduce the current fat and sugar content in most chocolate products should be explored.

Off The Cuff

Bird flu fear as strain mutates
Avian flu shows signs of a resurgence, while a mutant strain - able to sidestep vaccines - could be spreading in Asia, the United Nations warns.

Psoriasis 'linked to stroke risk'
People with psoriasis have nearly three times the normal risk of stroke and abnormal heart rhythm, according to scientists in Denmark.
A study of 4.5 million people, published in the European Heart Journal, showed the highest risk was in young patients with severe psoriasis.

Michigan court: Law doesn’t allow pot sales
An appeals court has ruled that Michigan’s medical marijuana law doesn’t permit sales between registered patients.
An appeals court has ruled that Michigan’s medical marijuana law doesn’t permit sales between registered patients.
The ruling, in a case that had been brought against a pot dispensary operated by owners legally allowed to possess and grow the drug, allows local authorities to close similar shops, Reuters reports.

According to the Associated Press:
Compassionate Apothecary, and owners of the mid-Michigan company, claimed they weren’t doing anything illegal because the law allows the “delivery” and “transfer” of marijuana. The business allows its 345 members to sell marijuana to each other, with the owners taking as much as a 20 percent cut. In less than three months, Compassionate Apothecary earned $21,000 before expenses after opening in May 2010.

“The ‘medical use’ of marijuana does not include patient-to-patient ‘sales’ of marijuana. Defendants, therefore, have no authority under the (law) to operate a marijuana dispensary that actively engages in and carries out patient-to-patient sales,” said appeals court judges Joel Hoekstra, Christopher Murray and Cynthia Diane Stephens.

“This ruling is a huge victory for public safety and Michigan communities struggling with an invasion of pot shops near their schools, homes and churches,” State Attorney General Bill Schuette said in a statement. “The court echoed the concerns of law enforcement, clarifying that this law is narrowly focused to help the seriously ill, not the creation of a marijuana free-for-all.”
Michigan is one of 16 states that, along with the District of Columbia, allow marijuana to be used to ease medical conditions. According to the South Bend Tribune, there are an estimated 200 to 300 marijuana dispensaries in Michigan serving the state’s 99,500 residents with medical marijuana cards.