HCV New Drugs And Liver Health

Sorafenib benefits select HCC patients with cirrhosis

2012-05-25T21:46:00.000-04:00

By Will Boggs MD

NEW YORK (Reuters Health) – Single-agent sorafenib improves outcomes for select patients with advanced hepatocellular carcinoma (HCC) and underlying Child-Pugh B liver cirrhosis, researchers from Hong Kong report in the April 19th online issue of Cancer.

“I would only recommend prescribing sorafenib to patients with score 7 instead of 8-9, as most benefits are seen in score 7 patients,” Dr. Thomas Yau from Queen Mary Hospital, Hong Kong, China told Reuters Health in an email.

Although sorafenib is FDA-approved as first-line treatment for advanced HCC, its efficacy and tolerability remain largely unknown for patients with suboptimal liver function.

Dr. Yau and colleagues explored that question in a retrospective study of three groups of patients with advanced HCC: 108 with Child-Pugh A cirrhosis (CPA), 37 with Child-Pugh B disease and a score of 7 (CPB7), and 27 with scores of Child-Pugh B and scores of 8-9 (CPB8-9).
Patients in Child-Pugh class A have well compensated disease. Child-Pugh B indicates significant functional compromise. (Child-Pugh class C patients, not included here, have decompensated liver disease.)

The overall clinical benefit rates (complete response + partial response + stable disease) did not differ significantly between patients with CPA, CPB7, or CPB8-9 (23.3%, 32.4%, and 14.8%; p=0.23).
Median progression-free survival was also similar — 3.2 months for CPA, 3.2 months for CPB7, and 2.3 months for CPB8-9 — but median overall survival was significantly greater for CPA and CPB7 than for CPB8-9 (6.1 and 5.4 vs 2.7 months; p=0.02).

Rates of most nonhematological and hematological adverse events were comparable in the three groups. There were, however, significantly more GI bleeding events and hepatic encephalopathy in CPB patients than CPA patients.

More CPB than CPA patients had drug termination due to adverse events, primarily related to more cirrhotic complications in CPB (15.6%) than CPA (5.6%) patients during sorafenib treatment.
“Therefore,” the researchers suggest, “when sorafenib is routinely used to treat advanced HCC patients with CPB cirrhosis, more vigilant surveillance and follow-up is advisable.”

“The on-going GIDEON (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib) study will certainly provide us more information about the efficacy and safety of sorafenib use in patients with Child Pugh B cirrhosis,” Dr. Yau said. “We are planning to explore the potential benefits and safety of using sorafenib in other advanced HCC subgroups, such as patients with ECOG 3/4.”

The study was supported by the University of Hong Kong hepatocellular carcinoma research fund.

SOURCE: http://bit.ly/KDr7pd

http://www.thedoctorschannel.com/view/sorafenib-benefits-select-hcc-patients-with-cirrhosis/

Amgen’s incomplete report on an early major trial of epoetin misled the medical community about the anemia drug’s risks and benefits

2012-05-25T21:13:00.004-04:00

stock.xchng, gerard79

*EPOGEN® (epoetin alfa)

News & Opinion

Opinion: Misleading Drug Trials

Amgen’s incomplete report on an early major trial of epoetin misled the medical community about the anemia drug’s risks and benefits—and helped make Amgen rich.

By Daniel W. Coyne | May 14, 2012

The Normal Hematocrit Trial, conducted in the mid-1990s, was the largest study ever to compare the use of epoetin, a drug that stimulates blood production, to treat dialysis patients, who suffer from anemia, or a below-normal red blood cell count, called hematocrit. In healthy individuals, 39 to 45 percent of their blood is comprised of red blood cells. Severe anemia, a hematocrit below 25 percent, can stress heart function, cause marked fatigue, and require blood transfusions.

Most dialysis patients need some epoetin or a similar drug to avoid severe anemia, and the higher the desired hematocrit, the higher the dose required. The study aimed to compare the effects of standard epoetin doses, which maintain patients’ hematocrit around 30 percent, and much higher doses, to raise hematocrit to normal (42 percent). The trial was stopped early in May 1996, just 29 months after it began, because of a trend toward increased deaths and heart attacks in the patients given the higher doses of epoetin. This was the first outcomes trial to show epoetin might be harmful. An editorial accompanying the August 1998 publication of the study in the New England Journal of Medicine, described how, “disappointingly,” there was a trend toward more deaths in the higher dosage group, but argued that the study still supported the recommendations of the National Kidney Foundation’s guidelines, published in the year before, that sufficient epoetin be used to maintain hematocrit between 33 and 36 percent—the upper half of the US Food and Drug Administration’s recommendation at that time—to reduce transfusions, improve quality of life, and possibly reduce deaths.

In March 2012, 14 years later, I published my own analysis of the trial based on Amgen’s clinical trial report, which I obtained through a Freedom of Information Act request. The results were dramatically different.

In 1998, although the risk of death and heart attack was significantly greater among patients receiving the higher doses of epoetin, the NEJM editors reportedly accepted Amgen’s position that the statistics should be adjusted because the company and the trials’ leaders terminated the trial early based on the recommendation of the data safety monitoring board. Therefore the trial results were reported as showing only a trend toward—and not solid evidence for—increased harm. The 1998 paper did not report the unadjusted statistics, or state that the statistical rules employed required the p value to reach 0.00088 to be considered significant, a much high bar than the traditional 0.05. This was also not appreciated by most experts.

According to the 1998 NEJM publication, the only definitive risk from higher epoetin doses was an increased risk of clotting the fistula from which blood is taken to perform hemodialysis, a common and less severe problem. And the higher dose group benefited by receiving fewer transfusions and enjoying higher measures of the “physical function” component of quality of life.

Thus, while the 1998 NEJM publication discouraged high epoetin doses to target hematocrit to 42 percent because of a trend toward increased risks, it also identified clear benefits of exceeding a hematocrit target of 30 percent—fewer transfusions and better quality of life. Epoetin use had already started to increase following the release of National Kidney Foundation’s 1997 KDOQI anemia guidelines, which incidentally, were funded by Amgen. After the NEJM paper was published, epoetin use in dialysis patients exploded, becoming a $2.5 billion a year market in the US alone.

By 2006, new KDOQI guidelines, again supported by Amgen, recommended all dialysis and kidney disease patients should receive doses of epoetin to maintain a hematocrit of 33 to 39 percent based on quality of life improvements—citing as evidence the Normal Hematocrit Trial and some smaller trials.

The results of my own analysis, on the other hand, published this March in Kidney International, showed that the quality of life scores had not improved in the higher dosing arm. The results I found in the Amgen report, filed with the FDA in 1996, showed that bigger epoetin doses to target higher hematocrit did not improve the physical function quality of life component at all, and had significantly increased the risk of death, heart attack, other thrombotic events, and hospitalizations.

The only benefit from higher epoetin doses was reduced transfusions, though the benefit was minor: one needed to treat 10 patients for 14 months at an additional epoetin cost of about $200,000 to avoid one person being transfused. Increased hospitalizations would further increase the total cost of higher epoetin doses.

The strikingly different results were because the 1998 NEJM publication had replaced the predefined outcomes and analyses with statistical adjustments and post hoc assessments, including replacing the total lack of effect of higher doses on physical function scores with the observation that patients with higher physical function scores had higher hematocrit, presumably because healthier patients respond better to epoetin. The wording was sufficiently unclear that even the KDOQI anemia guidelines misread the quality of life results as indicating that higher doses of epoetin to target higher hematocrit had caused an improvement in quality of life, when in fact, the trial results showed no improvement.

The academic authors of the 1998 publication state there was no intent to mislead, claiming the NEJM editors removed from drafts all the adverse results that I reported in 2012. They also state the 1998 publication clearly discouraged targeting hematocrit to 42 percent. What the 1998 publication did not do, however, was make clear, as my report does, that higher epoetin doses carry great risks, while the only benefit was a meager reduction in transfusion risk at great monetary cost.

Of course, even if there was no intentional deception, the effect was to force experts to say targeting hematocrit to about 42 percent using higher epoetin doses improved quality of life and reduced transfusions, and prevented them from saying such management significantly increased deaths, cardiac events, thrombotic events, and hospitalizations. Amgen controlled the debate, and by 2012 had made $37 billion from epoetin sales in the United States alone.

And if the intent was not to mislead, why not just publish subsequent articles clarifying the results, especially the quality of life results? The anemia workgroups that developed the KDOQI guidelines included one of the 1998 NEJM authors. Why not notify the KDOQI organization and other workgroup members that they were misreading the 1998 NEJM results? I cannot imagine what Amgen would have done if they had intended to mislead.

I waited 1,260 days to receive the trial report from the FDA. Two weeks before receiving the report, on June 24, 2011, the FDA released a safety warning and new label advice for use of epoetin in chronic kidney disease. It withdrew the previous recommended dose and hematocrit target of 30-36 percent. The new label states that there is no known safe dose of epoetin, no proven safe hematocrit target, and when using epoetin in dialysis patients, decrease or stop the epoetin when hematocrit exceeds 33 percent. The label now reports the Normal Hematocrit Trial’s hazard ratio and confidence intervals for death and heart attack and all-cause death as significantly higher in the higher hematocrit arm, just as I reported them earlier this year.

Finally, as strange as it seems, I am now the sole author of the publication on the predefined primary and secondary results of the largest outcomes trial of epoetin in dialysis patients, and I didn’t even participate in the trial. Perhaps the FDA will make the epoetin label cite my paper.

Daniel Coyne is a Professor of Medicine at Washington University School of Medicine in St. Louis, Missouri.

http://the-scientist.com/2012/05/14/opinion-misleading-drug-trials/

Improved treatment coming for HIV/ HCV co-infection

2012-05-25T19:34:00.000-04:00

DDW Daily News

Improved treatment coming for HIV/ HCV co-infection

May 22, 2012

Interim results from Phase 2b trials of direct-acting antiviral therapy in patients co-infected with HIV and HCV are showing promising results. So promising, in fact, that it may be time to alter treatment.

“We have tantalizing data from two trials,” said John Vierling, MD, FACP, professor of medicine and surgery at the Baylor College of Medicine, Houston, TX. “I would encourage enrollment in Phase 3 trials that are now open rather than individual, off-label use of these agents.”

Dr. Vierling was the lead speaker for a Monday afternoon symposium on Liver Disease in Patients with HIV Infection sponsored by the AASLD.

HCV has emerged as a significant clinical problem among patients infected with HIV, Dr. Vierling noted. About a third of HIV patients in the U.S. are coinfected with HCV.

“The success of HIV therapy in reducing viral loads and extending life has led to the recognition that liver disease is a significant comorbidity with HIV,” he said. “HCV infection, in particular, is associated with increased morbidity and mortality from liver disease in patients with HIV.”

The primary goal in treating these co-infected individuals is to prevent progression to cirrhosis. In patients who already show signs of cirrhosis, the goal is to prevent progression to liver cancer or the need for liver transplantation.

Boceprevir and telaprevir have been approved for the treatment of HCV genotype 1, which is responsible for about 75 percent of HCV infection in the U.S. and about 90 percent of HCV infection among African Americans. Trials for HIV/HCV co-infection are less advanced.

Boceprevir

An interim analysis of boceprevir plus peginterferon/ribavirin (PR) versus PR alone was reported in April. Early trials suggested that the combination is more effective than PR alone, but questions remain about the safety and efficacy of the combination.

The interim analysis assessed treatment results after 12 weeks, Dr. Vierling said. The trial was relatively small — 64 patients randomized to boceprevir/PR and 34 to PR alone. Patients in both arms were in early middle age, he said, predominantly male and white. There was a very low incidence of cirrhosis — just 3 percent in the PR arm and 6 percent in the boceprevir/PR arm.

All of the patients enrolled in the trial received at least one treatment. In the PR arm, 18 patients (53 percent) discontinued and 12 patients (35 percent) completed treatment. The other four patients crossed over to the boceprevir/PR arm after a futility analysis. In the boceprevir/PR arm, 24 patients (38 percent) discontinued and 40 (63 percent) completed treatment.

At four, eight, 12, and 24 weeks, the sustained viral response was higher in the boceprevir/PR arm. The sustained viral response rate at 12 weeks, the intended interim endpoint, was 60.7 percent in the boceprevir/ PR arm and 26.5 percent in the PR arm.

There were also three HIV breakthroughs in the boceprevir/PR arm, all of them at week 24 or later in the trial. Pharmacokinetic data show drug-drug interactions between boceprevir and multiple antiretroviral agents. It may be appropriate to adjust antiretroviral dosing to account for the interactions, Dr. Vierling said.

There were no major differences in safety profiles between the two arms, with no deaths in either arm and adverse events in 100 percent of patients in the PR arm compared to 98 percent in the boceprevir/PR arm. There were some differences in side effects but no surprises, Dr. Vierling said.

“These adverse events are not unique to the co-infected population,” he said. “They are very similar to the adverse events we see in the moninfected population.”

Telaprevir

Telaprevir plus PR showed similarly positive results compared to PR alone. Dr Vierling reviewed interim findings from the Phase 2 Study 110 trial first released in March 2012.

The Study 110 trial included patients who were on antiretroviral therapy (ART) and patients who were not on ART. Of the patients on ART, 74 percent on telaprevir showed sustained viral response at 12 compared to 45 percent of patients on PR alone. The results were similar in patients not on ART — 71 percent in the telaprevir arm showed sustained viral response compared to 33 percent for PR only. Three of the telaprevir patients showed HVC breakthrough, but there were no HIV viral load rebounds in either group.

“The rates of efficacy are quite encouraging for both of these trials, as are safety and tolerability,” Dr. Vierling said.

DDW-Metformin Shows Dose-Dependent Risk Reduction of HCC in Patients With Diabetes

2012-05-25T19:14:00.000-04:00

DGDispatch

Metformin Shows Dose-Dependent Risk Reduction of HCC in Patients With Diabetes: Presented at DDW
By Nancy A. Melville

SAN DIEGO -- May 25, 2012 -- Metformin shows a dose-dependent chemopreventive effect in reducing the risk of hepatocellular carcinoma (HCC) at a rate of about 7% per year, researchers said here at the Digestive Disease Week (DDW) 2012.

Metformin has been linked with HCC in past research involving patients with other conditions, said lead author Chun-Ying Wu, MD, Yang-Ming University in Taipei, Taiwan

"Previous studies have shown a relationship between HCC and metformin, and in a prospective cohort of cirrhotic patients with hepatitis C, metformin use was associated with significantly reduced HCC risk," he said on May 21.

Several mechanisms are believed to provide the benefit, Dr. Wu added. "Whereas insulin resistance plays a role in hepatic carcinogenesis via activation of the IGF-1 signalling axis and increased fat accumulation in hepatocytes, metformin has been shown to improve insulin sensitivity, inhibit hepatic gluconeogenesis and decrease glycogenolysis."

In the new study, the research team evaluated 97,430 patients diagnosed with HCC between 1997 and 2008 who were enrolled in Taiwan's National Health Insurance Research Database and 194,860 age, gender, and physician visit date-matched controls.

The patients with diabetes not using metformin showed the highest risk of HCC (adjusted odds ratio [OR] = 1.95). This was followed by patients with diabetes who rarely used metformin (OR = 1.74), and then by those who frequently used metformin (OR = 1.67) and those who regularly used metformin (OR = 1.56).

Each incremental year increase in metformin use resulted in a 6% to 7% reduction in the risk of HCC in patients with diabetes.

"In the nationwide population study, we found that use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner," Dr. Wu concluded. "Using metformin in diabetic patients to decrease the risk of HCC should be recommended."

Digestive Disease Week 2012 is cosponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

[Presentation title: Metformin Decreases Hepatocellular Carcinoma Risk in a Dose-Dependent Manner: Population-Based and in Vitro Studies. Abstract 596]

Vertex Announces Webcast of its Presentations at Two Investor Conferences

2012-05-25T18:49:00.000-04:00

Vertex Announces Webcast of its Presentations at Two Investor Conferences

By: Vertex Pharmaceuticals Incorporated via Business Wire News Releases

Posted on May 25, 2012 at 16:15 PM EDT

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that Vertex will webcast its presentation at the Sanford C. Bernstein Strategic Decisions Conference on Wednesday, May 30, 2012 at 8:00 a.m. EDT and at the Goldman Sachs Global Healthcare Conference 2012 on Wednesday, June 6, 2012 at 1:20 p.m. PDT (4:20 p.m. EDT).

The presentations will be webcast live and may be accessed from ‘Events & Presentations’ on the home page of Vertex’s website at www.vrtx.com. A replay of the webcasts will also be available on the Company’s website for two weeks following the presentations. To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast.

About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Sciencemagazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Vertex’s press releases are available at www.vrtx.com.

Contacts:
Vertex Pharmaceuticals Incorporated
Michael Partridge, 617-444-6108
Vice President, Investor Relations

DDW- Fatty Liver Disease on Rise in Teens

2012-05-25T18:04:00.000-04:00

Medpage Today DDW Coverage

Fatty Liver Disease on Rise in Teens

By Kristina Fiore, Staff Writer, MedPage Today Published: May 25, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points
+This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
+Data from the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2008 showed an increase in non-alcoholic fatty liver disease among adolescents.
+Note that elevated serum ALT increased substantially in obese children over this time frame

SAN DIEGO -- The prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has risen over the last few decades and now affects about one in 10 children, researchers said here.

From 1988 to 2008, the prevalence of NAFLD rose from 3.6% to 9.9% among children ages 12 to 18 (P<0.001), Miriam Vos, MD, of Emory University in Atlanta, and colleagues reported during a press briefing at Digestive Disease Week here.

Vos added that additional data from 2009 and 2010, however, have shown a potential flattening in that trend.

Still, she said, the data "point to the importance of continued study [of this condition in this population], particularly for prevention, because just like obesity, this disease is much easier to prevent than to treat."

NAFLD is the most common liver disease in children, and has been tied to further complications down the road, including diabetes, hypertension, and cancer.

Researchers have suspected that there's been an increase in the number of cases of NAFLD among pediatric patients in recent years, "but one of the challenges with that is, we're all looking for it more often because awareness has also been increased," Vos said.

So she and colleagues looked at data from the National Health and Nutrition Examination Survey (NHANES) 1988-2008 on 10,359 patients ages 12 to 18.

NAFLD was defined as being overweight or obese (having a body mass index [BMI] in the 85th percentile or higher) and having an elevated ALT (one that is above 25.8 for boys or above 22.1 for girls).

They found that the prevalence of NAFLD in this pediatric population rose significantly during the course of the study. Among overweight children, the prevalence of elevated ALT was 13.2% in 2008, with no significant increases over time, but in obese children, that prevalence jumped a significant 120% over the study period, from 16.7% to 36.9% (P=0.006).

Vos said the overall increase in pediatric NAFLD prevalence wasn't just determined by the prevalence of obesity or overweight in the sample. In fact, she said, NAFLD "seems to be increasing faster than the prevalence of obesity."

To understand why, they conducted further analyses and found that there's been an increase in average BMI in obese and overweight categories, and also in mean waist circumference in those categories.

"That seemed to nicely parallel the increase in NAFLD," she said. "That may be because an increase in belly fat or abdominal weight is very closely correlated with fatty liver disease."

Vos noted, however, that in additional data from 2009 and 2010, it seems that the trend may be flattening or even slightly improving. "It's not statistically significant, but I'm optimistic this is going to lead to good news in years to come," she said.

Nonetheless, she and colleagues concluded that the data strongly support recommendations to screen for NAFLD in obese adolescents.

The researchers reported no conflicts of interest.

Primary source: Digestive Disease Week
Source reference:
Vos MB, Welsh J "Prevalence of suspected NAFLD is increasing among U.S. adolescents" DDW 2012; Abstract 705.
--------------------------------------------------------------------------------

Staff Writer

Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine.

Medpage Today DDW Coverage

2012 - Update on the Diagnosis and Treatment of Hepatitis C

2012-05-25T17:32:00.000-04:00

Clinical Reviews

Gastroenterology & Endoscopy News

ISSUE: MAY 2012 | VOLUME: 63:5

Update on the Diagnosis and Treatment of Hepatitis C

by Arun B. Jesudian, MD and Ira M. Jacobson, MD

Hepatitis C virus (HCV) infection is a national and global public health concern, affecting up to 4 million individuals in the United States and 200 million individuals worldwide. Despite a declining incidence of new HCV infections in the United States, the prevalence of advanced liver disease secondary to chronic HCV infection, including cirrhosis and hepatocellular carcinoma, is expected to rise in the coming years.

Download to read this article in PDF document:
Update on the Diagnosis and Treatment of Hepatitis C

This article is in PDF format and it requires Abobe Reader. If you do not have Adobe Reader installed on your computer then please download and install from the link below.

Download Adobe Reader

http://www.gastroendonews.com/NewsArticles.aspx?d=Clinical+Reviews&d_id=192

Franck’s Compounding Pharmacy Sterile Preparations: Reports of Fungal Endophthalmitis, Expanded Recall

2012-05-25T09:55:00.001-04:00

Franck’s Compounding Pharmacy Sterile Preparations: Reports of Fungal Endophthalmitis, Expanded Recall

Featured In: Regulatory News

[Posted 05/24/2012]

Ophthalmology, Urology, Primary Care, Pharmacy

FDA is notifying all physicians and medical care organizations who have ordered any compounded product sold as a sterile preparation by Franck's Compounding Pharmacy of Ocala, Florida, of the recall of all sterile products sold by Franck's since November 2011 due to the possibility of lack of sterility.

The recall is being carried out to the user physician. An active investigation of this matter by the CDC and FDA is ongoing at this time. In March 2012, FDA received reports of fungal endophthalmitis (eye infections) in patients who were given Brilliant Blue G (BBG), supplied by Franck's Pharmacy, during eye surgeries. Clinicians in several states reported the adverse events. In April 2012, FDA received reports of eye infections in patients who were given injections of Franck’s drug products containing triamcinolone during eye surgery.

FDA advises that any product received from Franck's since November 2011 not be used and customer/physicians follow the instructions provided by Franck’s. FDA also recommends that any adverse events suspected to be associated with use of the products be reported to FDA:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form 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

[05/24/2012 - Press Release - Franck's Compounding Pharmacy]
[05/04/2012 - MMWR Weekly Report - CDC]
Previous MedWatch Alerts:
SOURCE

Related-May 04 2012

CDC links eye infections to troubled Florida pharmacy
Published May 04, 2012

Federal health officials confirmed 33 cases of a rare fungal eye infection across seven states on Thursday, stemming from products mixed in a Florida pharmacy that also mixed supplements that killed 21 elite polo horses in 2009.

The patients had all undergone some type of eye procedure, including surgery or injections. Twenty-three suffered some degree of vision loss and 24 patients had to undergo another eye surgery, according to a report from the Centers for Disease Control and Prevention.
Health officials traced many of the cases to a dye and an injection including triamcinolone and other products from Franck's Compounding Lab in Ocala. The Food and Drug Administration tested unopened bottles and unused syringes of the dye collected, finding multiple bacterial and fungal species.

California health officials first alerted the CDC after nine patients developed the eye infection in March. Franck's recalled dye lots that same month. A single lot of triamcinolone was recalled on Mar. 31.

CDC officials said the investigation to identify the root cause is ongoing and warned doctors and patients to stay away from "compounded products labeled as sterile from Franck's," according to the report.

The pharmacy has not recalled or halted production of other sterile compounded products, which chemotherapy and other injectables.

Pharmacy officials said in a statement they have conducted a thorough investigation and traced the cause of the contamination to a dye used in eye injections of triamcinolone and formulas containing that drug.

The pharmacy says it has resolved the issue and made several changes, including hiring a new pharmacist to oversee quality assurance. It says it has cooperated with federal health officials "in an effort to isolate the source of contamination and prevent future occurrences."
Compounding is a process in which pharmacists mix drugs using bulk ingredients. Patients usually turn to compounders when they are allergic to inactive ingredients in FDA-approved medicines. They are also used when a patient needs a different dose or a different form of delivery — such as a cream, powder or injectable liquid — than what is commercially available.

State health officials said they can't confirm whether they are investigating Franck's or any pharmacy until 10 days after the alleged investigation and only if probable cause is found. If they do determine a pharmacy poses an immediate threat, the agency can immediately suspend the facility's license.
Franck's came under intense scrutiny in 2009 after 21 polo horses died before a championship match near West Palm Beach. The horses from the Venezuelan-owned Lechuza Caracas team had just been given a cocktail of vitamins and minerals compounded by the pharmacy on order from the team's veterinarian.

Franck's later acknowledged using too much selenium in the mix. Florida's top veterinarian blamed the deaths on an overdose of the mineral often used to help horses recover from fatigue.
The horses' owners have since filed a lawsuit against the pharmacy.

Following the horse deaths, the FDA accused Franck's of illegally creating copies of similar drugs. The agency also says the pharmacy is mixing brews outside of federal guidelines and is compounding animal products from drugs that have not been approved for use in the U.S. Officials warned pharmacies can circumvent the statutory drug approval process by manufacturing drugs under the guise of pharmacy compounding.

The FDA says Franck's was also warned in 2005, four years before the horses' deaths, that it was compounding animal drugs illegally. The agency warned the pharmacy again in December 2009, according to the complaint.

But a federal court disagreed with the FDA in 2011, ruling the agency did not have jurisdiction over the longstanding practice of pharmacists filling veterinary prescriptions for animals by compounding from bulk substances.

Read more: http://www.foxnews.com/health/2012/05/04/cdc-links-eye-infections-to-troubled-florida-pharmacy/#ixzz1vtusuSre

Liver Transplant Outcomes Improving in Europe

2012-05-24T21:47:00.000-04:00

From Reuters Health Information

Liver Transplant Outcomes Improving in Europe

By David Douglas
NEW YORK (Reuters Health) May 23 - Outcomes of liver transplantation for acute liver failure (ALF) in Europe have improved over two decades, according to a report online April 18th in the Journal of Hepatology.

And Dr. Andrew K. Burroughs, the senior author of the report, told Reuters Health by email that "results are improving despite poorer quality of donors, so this is a major achievement in the transplantation field."

Dr. Burroughs of University College London and colleagues analyzed donor, graft and recipient variables from the European Liver Transplant Registry database on 4,903 adults transplanted between 1988 and 2009.

For example, one-, three-, and five-year patient survival rates were 66%, 62%, and 61%, respectively, from 1988 to 1993, 75%, 72% and 70% from 1999 to 2003, and 79%, 75% and 72% between 2004 and 2009.

Patient survival rates in that most recent period were significantly better than in 1999-2003 (p=0.01), 1994-1998 (p=0.001), and 1988-1993 (p<0.001).

There were similar findings for graft survival. One-, three-, and five-year graft survival rates were only 51%, 47%, and 45%, respectively, from 1988 to 1993. By 2004 to 2009, those rates were 73%, 68%, and 63%, respectively.

The improved results from 2004 to 2009 were particularly noteworthy as the proportions of donors older than 60 rose from 1.8% in 1988-1993 to 21% most recently.

The authors also found that transplants for acute liver failure due to acetaminophen overdose increased seven-fold over the study period, from 2% to 14.1%. Close to 8% of these patients died or lost their grafts chiefly because of suicide or non-adherence to immunosuppressive medications. More than half of these events were in the first year.

Factors associated with poor outcomes included acetaminophen-related acute liver failure (relative risk 1.24), reduced-size grafts (RR, 1.43), recipient age above 50 (RR, 1.26) and ABO-incompatible grafts (RR, 2.04).

In prognostic models constructed by the authors, recipients older than 50 years who received grafts from donors older than 60 years would have 57% mortality/graft loss within the first year.
Dr. Burroughs added that despite the overall improvement, "there may be a group of patients whose characteristics make them unlikely to survive with a poorer quality donor and this may influence practice."

SOURCE: http://bit.ly/K8I2nY
J Hepatol 2012.

DDW-Many Livers 'Too Fat' For Transplant

2012-05-24T21:36:00.000-04:00

By Kristina Fiore, Staff Writer, MedPage Today
Published: May 24, 2012

Reviewed by Robert Jasmer, MD;
Associate Clinical Professor of Medicine, University of California, San Francisco.

SAN DIEGO -- Increases in factors associated with fatty liver disease may be leading clinicians to discard more donated organs, researcher found.

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Increases in factors associated with fatty liver disease may be leading clinicians to discard more donated livers.
• Point out that over the past few years there's been a decline in the number of liver transplants done, but that decline isn't explained by flat donation rates alone.

In an analysis of data from the United Organ Sharing Network (UNOS), age, obesity, diabetes, and hypertension were associated with an increased risk of a liver being discarded, Eric Orman, MD, of the University of North Carolina at Chapel Hill, and colleagues reported during a press briefing at Digestive Disease Week here.

"We're actually throwing out livers that in the past may have been able to be used ... [because] of all these factors associated with fatty liver disease," Orman explained.

Orman said that over the past few years, there's been a decline in the number of liver transplants done, but that drop isn't explained by flat donation rates alone.

"Although donation rates have decreased overall, they haven't decreased to the same extent as the decline in the number of livers transplanted," he said, adding that one explanation may be an increase in discard rates due to poor quality of organs.

So he and colleagues conducted a retrospective study of data from UNOS between 1994 and 2010 totaling 93,232 organ donors. Living donors, split livers, and donors with a body mass index of less than 14 or more than 50 kg/m were excluded.

Among the nearly 94,000 donors, 75% of livers were transplanted and a quarter of livers were not used.

They found that the number of discarded organs was stable until 2003 (with a total of 1,058 organs discarded in that last year), and then rose to 1,828 by 2010.

In a bivariate analysis, they found that discarded livers more often came from donors who were older (median 49 versus 43 years), obese (35% verses 22% of non-obese donors), diabetic (35% versus 24% of nondiabetics), and hypertensive (31% versus 22% of normotensive patients).

Discard rates were also higher in donation after cardiac death, which is different from standard procurement. In the latter, a patient is declared brain dead but kept on a ventilator to keep the organs perfused (65% versus 22%). In donation after cardiac death, perfusion of blood to the organs is disrupted.

In multivariate analysis, the researchers found that all of the previous factors were associated with a liver being discarded:

Age (OR 1.03 for each year increase, 95% CI 1.03 to 1.04)
Obesity (OR 1.92, 95% CI 1.82 to 2.03)
Diabetes (OR 1.42, 95% CI 1.32 to 1.53)
Hypertension (OR 1.15, 95% CI 1.08 to 1.22)
Donation after cardiac death (OR 12.3, 95% CI 11.3 to 13.4)

The researchers also saw significant increases in median donor age (40 to 46) and the prevalence of obesity (13% to 31%) during the study period, along with significant increases in diabetes (3% to 13%), hypertension (22% to 39%), and donation after cardiac death (2% to 12%).

They estimated that in 2010, 44% of discards were due to increased age, 9% to obesity, 5% to diabetes, and 5% to hypertension. These proportions were stable over time, they said.

On the other hand, the proportion of livers discarded due to donation after cardiac death rose from 0.2% in 2000 to 26% in 2010, suggesting an increasing reluctance to use these grafts, they reported.

Orman said that, overall, the findings are important "because if these trends continue, we're going to see further declines in liver transplant."

Kenneth Andreoni, MD, a UNOS committee member, said the increasing prevalence of comorbidities in donors is a "double-edged sword" because it reflects the fact that public health messages about safety are getting through to younger people, even though that may mean fewer quality donors.

"We're seeing fewer young people dying in traumas, but we're getting less high-quality, excellent organs," Andreoni told MedPage Today. "The question is, how can we make the best use of more middle-age and older donors?"

When it comes to organs with fatty liver disease, some researchers have been trying to better quantify the type of fat in the liver so that surgeons can have a better idea of what's usable and what's not, said Andreoni, who is from Ohio State University in Columbus.

Improvements on the pathology side may also be needed, he said. For instance, pathologists may need to offer a more specific range in terms of the percentage of fat in the organ, so clinicians can more easily recognize if an organ needs to be discarded or not.

Other work has focused on whether there are better ways to protect a fatty liver so it has a better chance of working after it's transplanted. "Is there something you can put in during reperfusion, like an antioxidant, that will lead to better outcomes?" Andreoni said.

A co-author reported a relationship with Salix Pharmaceuticals

Primary source: Digestive Disease Week
Source reference:
Orman ES, et al "The number of grafts available for liver transplantation is decreasing as a result of increasing age, metabolic syndrome, and donation after cardiac death" DDW 2012; Abstract 841.

Kristina Fiore

Staff Writer
Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine

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