Thursday, December 22, 2011

Hepatitis News Ticker-FDA Okays Raltegravir for Kids, Teens With HIV

Liver Cancer

Guidelines for diagnosis and treatment of hepatocellular carcinoma
A study in the latest Journal of Gastroenterology & Hepatology critically appraises clinical practice guidelines for diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third most common reason for cancer-related death worldwide.

Many countries either lack appropriate clinical practice guidelines for the diagnosis and treatment of hepatocellular carcinoma or the quality of their guidelines has never been evaluated.

Dr Tim Greten and colleagues from Germany identified published hepatocellular carcinoma guidelines, and assessed their quality with the Appraisal of Guidelines for Research and Evaluation instrument (AGREE) and their suitability regarding adaptation for future guidelines.

The research team performed a systematic literature search on hepatocellular carcinoma clinical practice guidelines of MEDLINE, National Guidelines Clearinghouse and the Guidelines International Network.

Guidelines performed well in the clarity domain with a mean score of 67%
Journal of Gastroenterology & Hepatology
Methodological quality of selected guidelines was assessed by the AGREE instrument, Version 2001.

The team screened a total of 286 citations were screened, and 32 relevant guidelines were identified.

Overall, the guidelines performed well in the clarity and presentation domain with a mean score of 67%, followed by scope and purpose, and rigor of development.

In contrast, poor scores were given for the remaining domains, including stakeholder involvement, applicability, and editorial independence.

According to the AGREE instrument, the research team recommended 4 guidelines, 18 with provisos and alterations while the remaining cannot be recommended for adaptation due to poor methodological quality.

Dr Greten's team concludes, "Although existing hepatocellular carcinoma guidelines may accurately reflect agreed clinical practice, many guidelines lack proper methodological quality. Future guidelines should place more emphasis on these methodological shortcomings."
J Gastroenterol Hepatol 2011: 26(12): 1779–1786
22 December 2011


FDA Okays Raltegravir for Kids, Teens With HIV

By Michael Smith, North American Correspondent, MedPage Today
Published: December 21, 2011

The integrase inhibitor raltegravir (Isentress) can be used to treat HIV in children and adolescents ages two through 18, the FDA announced.

The decision expands the indication for the drug, which was approved for adults in 2007. As in the case of other anti-HIV drugs, raltegravir is used with two other medications in a triple-drug cocktail.

The drug, in pill form, is taken orally twice a day.

Raltegravir is available in a chewable form but -- because the two tablet formulations are not interchangeable -- the chewable pills are only approved for use in children two to 11. Older adolescents will use the adult formulation.

Evaluation of the drug as a pediatric medication began after its initial approval and researchers reported earlier this year it was effective, even in patients who had been previously treated without a good result.

Researchers said at the Boston Conference on Retroviruses and Opportunistic Infections that in a small study of 21 children ages two to five, 62% had undetectable virus after 24 weeks of therapy, even though previous treatment had left them with detectable HIV.

The FDA said approval of the expanded indication was based on a multi-center clinical trial of 96 children and adolescents two to 18 who had been previously treated. After 24 weeks of treatment, 53% had undetectable HIV in their blood.

Insomnia and headache were the most commonly reported adverse effects, but the frequency was similar to what is seen in adults.

One patient in the trial reported severe treatment-related insomnia and another had a drug-related skin rash. The FDA said the drug should be stopped in such cases.

Merck And The ADAP Crisis Task Force Announce New Agreement To Improve Access And Care For People With HIV

Merck (NYSE: MRK), known as MSD outside the United States and Canada, and the ADAP Crisis Task Force (ACTF) announced a number of new initiatives to help struggling state AIDS Drug Assistance Programs (ADAPs) continue to provide access to medicines to people living with HIV. This is the third major response from Merck and ACTF in the last four years, as the financial crisis for these critical state programs continues.

Merck has agreed to:

Again lower the price of ISENTRESS® (raltegravir) to eligible ADAPs, effective Jan. 1, 2012. The new price will be "frozen" and will be available as part of the existing Merck special pricing program through Dec. 31, 2013. Merck was the first company to freeze the price of an antiretroviral (ARV) therapy to ADAPs in 2003.

In addition, Merck and ACTF have agreed to the following initiatives:

Increasing support for the Welvista ADAP Program. After its initial year in 2010 and evaluation of current needs, Merck is increasing it operations funding and medication donations for the Welvista ADAP Program. The program helps address the medication needs of ADAP clients who are currently on state ADAP waiting lists by expediting access to HIV medicines through a simplified application process.

Working to optimize the use of comprehensive health insurance options available to persons with HIV. Between 2009 and 2010, the use of private insurance by ADAPs tripled to more than 110,000 persons. The National Alliance of State and Territorial AIDS Directors (NASTAD) reported about 40 ADAPs used ADAP funds to purchase health insurance or pay insurance premiums, co-payments and/or deductibles for individuals eligible for ADAP (provided the insurance has comparable formulary benefits to that of the ADAP). Merck and NASTAD will seek solutions that overcome barriers to more widespread use of such approaches, such as expanding enrollments in Medicare Part D, private insurance and pre-existing condition insurance plans (PCIPs).

ISENTRESS is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients. The label for ISENTRESS is based on analyses of plasma HIV-1 RNA levels through 96 weeks in three double-blind controlled Phase III clinical studies of ISENTRESS. Two of these studies were conducted in clinically advanced, three-class ARV [non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor (PI)] treatment-experienced adults and one was conducted in treatment-naïve adults. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response. The safety and efficacy of ISENTRESS have not been established in pediatric patients.

Merck and the ACTF maintain a mutual commitment to partner together to assess the situation and to find solutions that will provide relief to sustain ADAPs. The first ADAP response from Merck and the ACTF was announced in August 2008, and the second response was announced in May 2010. At the time of the latest response, it was both parties' expectation that those actions - including a special pricing program for ADAPs and price freeze for ARV medicines - would be sufficient until 2014. It is believed that, in 2014, the U.S. government's newly-expanded Medicaid program and subsidized private health insurance program, mandated by the Patient Protection and Affordable Care Act (PPACA), will provide sufficient, sustainable care to the majority of people served by ADAPs.

It has become clear within the last year that previous agreements coupled with current federal and state funding were not enough to sustain ADAPs until 2014. Merck's latest response was a result of discussions between Merck and the ACTF over the last few months, and reflects the continuing fiscal circumstances in the states and the unmet needs of people with HIV.

"On behalf of the nearly two hundred thousand clients that ADAPs serve, we applaud Merck for its continued commitment to HIV," said Dwayne Haught, spokesperson for the ACTF and manager of the Texas ADAP. "Merck's history of HIV research and development, responsible pricing and related efforts are consistent with its track record of working to help ensure access to treatments for the people most in need. We commend Merck for responding once again to the unprecedented fiscal need faced by state ADAPs by providing additional support to help provide people living with HIV access to HIV medicines."

"With our company's legacy in HIV over the last 25 years, we consider it our obligation to continue to work with the ADAPs on solutions that provide crucial support for uninsured and underserved people living with HIV," said Chirfi Guindo, vice president and general manager, Merck HIV Franchise. "It is imperative to act now, given the ongoing ADAP funding crisis. We applaud President Obama's recent announcements of enhanced federal support for ADAPs and state HIV programs, and look forward to working together on sustainable solutions through improvements in the health care delivery system."

"These actions come at a time when federal funding for ADAPs remains relatively flat compared to enrollment growth, and state funding continues to fluctuate, making it difficult for the ADAP programs to provide access and care to all the clients they need to serve," said Lynda Dee, spokesperson for the Fair Pricing Coalition. "The Fair Pricing Coalition commends Merck for its long-standing commitment to providing access to treatment and welcomes Merck's new initiatives to help with the current ADAP funding crises."

Important Selected Safety Information

Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction and toxic epidermal necrolysis. Immediately discontinue treatment with ISENTRESS and other suspect agents if severe hypersensitivity, severe rash, or rash with systematic symptoms or liver aminotransferase elevations develops and monitor clinical status, including liver aminotransferases closely.

Healthcare providers should know that during the initial phase of treatment, immune reconstitution syndrome can occur, which may necessitate further evaluation and treatment. Monitor for immune reconstitution syndrome.

The most common adverse reactions of moderate to severe intensity greater than or equal to two percent that occurred at a higher rate than the comparator were insomnia in treatment-naïve patients and headache in treatment-experienced patients. Intensities were defined as follows: Moderate (discomfort enough to cause interference with usual activity); or Severe (incapacitating with inability to work or do usual activity).

Grade 2-4 creatine kinase laboratory abnormalities were observed in patients treated with ISENTRESS. Myopathy and rhabdomyolysis have been reported. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions.


ISENTRESS is Merck's integrase inhibitor for the treatment of HIV-1 infection in treatment-naïve and treatment-experienced adult patients as part of combination therapy. ISENTRESS is currently the only approved integrase inhibitor for the treatment of HIV-1. ISENTRESS works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme and has demonstrated rapid antiviral activity. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. Other HIV-1 drugs in use inhibit two other enzymes critical to the HIV-1 replication process - protease and reverse transcriptase - but ISENTRESS is the only approved medicine that inhibits the integrase enzyme. ISENTRESS is now approved in combination therapy in more than 45 countries for use in treatment-naïve adult patients with HIV-1 and in more than 90 countries for use in treatment-experienced adult patients with HIV-1. Merck is continuing to move forward with filings in additional countries around the world.

Merck's patient assistance programs in the U.S.

The SUPPORT™ Program is a two-part program that consists of: (1) free reimbursement support services; and (2) a patient assistance program for eligible individuals who have been prescribed one or more Merck HIV medicines. One part of this free program provides personalized support and patient advocacy regarding individual reimbursement issues. In addition, the SUPPORT™ Program also offers a patient assistance program, which may provide Merck HIV medicines free of charge to eligible patients which may be delivered directly to the patient's home.

View drug information on Isentress.

Organ Donation

CDC: New Report of Hepatitis C From Donor Organ

By Laura Landro

A new report of disease transmission from an organ donor could fuel demand for more rigorous testing of donors, despite concern that such screening could rule out useable organs.

The Centers for Disease Control and Prevention reports today that a Kentucky man whose organs were donated after he died following a traumatic brain injury transmitted hepatitis C virus to recipients of two kidneys and one blood vessel tissue patch because of problems with testing...Continue reading..

Improving family consent in organ donation could save lives

Research published today in the British Journal of Anaesthesia suggests that organ donation rates in the UK could be increased if the current issues affecting declined consent are improved. At present, only 30% of the UK population are registered on the NHS Organ Donor Register (ODR). From 2003 to 2005, the overall consent rate for donation after brain death (DBD) was 59%. This figure remains largely unchanged with a consent rate of 63% for DBD in 2007-2009. The low consent rate for organ donation in the UK is the largest factor limiting actual organ donor.

Currently, organ donation consent is established by views expressed prospectively via membership of the ODR or views expressed to a family member. However, when a patient is deceased and has not previously expressed a wish to their relatives about organ donation the health care professional will discuss donation with the family. Up to 10% of families of potential donors, who are on the ODR, still refuse assent to donation. At present, it is accepted practice to respect the family's wishes despite the existence of valid legal consent.

The paper 'Consent for Organ Donation' by Vincent and Logan, published in a special issue regarding organ donation for the British Journal of Anaesthesia, calls for action on the concerns and issues that affect consent.

Make Your Donation Wishes Known:

Findings have consistently shown that only 50% of those that wish to donate after death have discussed this with a family member. It is extremely important that donors discuss their wishes with their close relative because ultimately it is the family which authorizes organ donation. Research has found that family discussion strongly predicts consent for donation from family members.

Recent research has examined the negative attitudes felt in joining the ODR and suggests that these may be the most important barriers to address. These include a level of disgust felt in the idea of organ procurement, a belief that registering for organ donation will jinx the individual; and mistrust of the medical profession. Addressing such negative beliefs should be a key component in public campaigns to increase donation.

Staff Care and Interaction:

The relative's experience and interaction with staff can have a huge impact on the decision to consent or refuse donation. The basic principles of medical practice should always be in place. However, a wider treatment of care for the family itself can have a very positive or negative effect on consent. Provisions of physical support in the form of comfortable accommodation, staff availability throughout the patient's admittance, empathy to the family, and a respectful and dignified treatment, are all factors that can have a positive impact on donation rates.

Make Sure the Family Understands

Understanding brain stem death is an important factor in organ donation. Studies have consistently found that an astounding amount of relatives do not fully understand brain death, even after it has been explained by the attending doctors. It is extremely important that brain stem death is explained so that a relative can fully understand that their loved one is dead before donation takes place. Once this understanding has been reached discussion and consent for organ donation can then begin. Specialist Nurses in Organ Donation are also trained and have the time to make sure families understand this. It has been suggested that allowing a family to witness tests or providing imaging or diagrams to explain concepts could help to improve a family's understanding of brain death.

Who should request consent?

It is intuitive that a specialist coordinator, with systematic training, a skill set that understands the modifiable factors and grief reactions of the family, and a day-to-day experience of dealing with such encounters, may perform better than a physician who may be involved in donation infrequently. Studies carried out by Shafer and colleagues suggest that early contact with families and interaction before any conversation about donation increased consent and authorisation rates. The study showed 75% consent rates for groups that had contact with a coordinator for more than 3 hours. Since 2009, the UK has expanded its pool of coordinators from 100 to 250. It is anticipated that the value and expertise the specialist nurses bring to the intensive care unit will become accepted more widely in areas where the model has not already been embraced.

Practical steps for improving consent:

  • Promote the need for families to discuss their wishes regarding organ donation
  • Discuss donation at a time separate to that when the family are informed of the death or its inevitability, in an unhurried manner
  • Ensure the family are given specific information and that in particular, concerning DBD, the concept of brain stem death is fully explained
  • Use an approach pre-planned by the coordinator/specialist nurse and healthcare team that considers specific individual circumstances

Dr. A. Vincent, author of 'Consent for organ donation', comments that "Only 60% of families when asked, give consent for organ donation from a loved one. Research would suggest that adopting a best practice model with respect to the process involved in consent for organ donation could improve this rate. It is an improvement in consent rates, more than in any other area, that would see a real increase in donor numbers in the UK."

Paul Murphy, National Clinical Lead for Organ Donation at NHS Blood and Transplant said: "Organ transplantation is made possible through the generosity of people who donate their organs so that others can live on, but also through the skill and dedication of a great many clinical staff. There has been much progress in recent years in transforming the systems and processes across the UK to increase rates of organ donation and transplantation, and there is more work needed to improve rates further.

NHS Blood and Transplant plays a key part in overseeing and managing donation and transplant processes and is privileged to have been involved in producing this supplement which brings together the professional views of many highly respected and experienced clinicians and showcases the work being done in the UK to increase donor numbers."

Note to Editors:

Any reference to this article must be attributed to British Journal of Anaesthesia published by OUP.

'Consent for organ donation' by A. Vincent and L. Logan. British Journal of Anaesthesia. doi:10.1093/bja/aer353

The paper can be accessed here:

Other Papers of interest on the subject of organ donation:

'International practices of organ donation' by C. Rudge, R. Matesanz, F. L. Delmonico and J. Chapman. British Journal of Anaesthesia. doi:10.1093/bja/aer399

'Respecting wishes and avoiding conflict: understanding the ethical basis for organ donation and retrieval' by B. Farsides. British Journal of Anaesthesia. doi:10.1093/bja/aer370


During this season of giving, Shane Campbell has already received one of the greatest gifts of all: the love and support of his community.

Now he's hoping for an equally amazing gift. The gift Campbell waits for might come next month when he visits the University of Washington Medical Center to see if he qualifies to go on the donor list to receive a liver.

On Sept. 11, days after his 43rd birthday, Campbell became deathly ill with chest pains. After exploratory surgery and a difficult recovery, he wound up taking a LifeMed Learjet to Seattle — a $75,000 air ambulance ride.

Eventually he got the diagnosis: end-stage liver failure. In mid-October, doctors gave him a one-in-four chance of living 90 days. What caused his liver disease, no one knows for certain.

He's been sober for 15 years and didn't drink much before that....

December 22, 2011, 7:54 AM

By Maya Schenwar

When congressional Republicans rammed through their disastrous consolidated spending bill last week, subsidizing abstinence-only education and granting $2 billion per week for the war in Afghanistan, they also locked in a regressive funding cut that would endanger the lives of many thousands of Americans. The bill reinstates a ban on federal funding for needle exchange programs — a ban that was repealed just two years ago, due to overwhelming evidence that the programs dramatically curb the spread of blood-transmitted diseases like HIV and hepatitis C.

Liver disease and hepatitis campaign begins 24 Dec.
TAIPEI--A campaign to raise awareness of hepatitis prevention will be held on Christmas eve in Taipei to raise funds for preventive care, a research organization said yesterday.

To encourage screening, people aged over 26 will be eligible for free hepatitis screening at the event, according to the Liver Disease Prevention and Treatment Research Foundation.

Since Taiwanese people born after 1985 have been vaccinated against hepatitis, they are on a lower priority list than those older than that, according to the foundation.

“There are about 3 million hepatitis B carriers in Taiwan,” said Sheu Jin-chuan, head of the foundation. “But only 30 percent of them are aware of their condition.”

The other 2 million, therefore, are at greater risk of developing more serious complications such as cirrhosis of the liver, he said, urging the public to pay more attention to their health by getting health checks.

As liver disease is often overlooked due to unclear symptoms, he said, only through regular screening can one ensure early diagnosis.

Healthy You

A commentary by Dr. David Spence of The University of Western Ontario and Dr. Meir Stampfer of the Harvard School of Public Health in today's Journal of the American Medical Association (JAMA) argues that vitamin therapy still has a role to play in reducing stroke.

Vitamin B therapy was once widely used to lower homocysteine levels. Too much of this amino acid in the bloodstream was linked to increased risk of stroke and heart attack. But several randomized trials found lowering homocysteine levels with B vitamins did not result in a cardiovascular benefit. And a study by Dr. Spence, a scientist with the Robarts Research Institute at Western's Schulich School of Medicine & Dentistry, found Vitamin B therapy actually increased cardiovascular risk in patients with diabetic nephropathy.

Dr. Spence says this commentary provides insights that overturn the widespread belief that "homocysteine is dead." He says two key issues have been overlooked in the interpretation of the clinical trials: the key role of vitamin B12, and the newly recognized role of renal failure.

"It is now clear that the large trials showing no benefit of vitamin therapy obscured the benefit of vitamin therapy because they lumped together patients with renal failure and those with good renal function. The vitamins are harmful in renal failure, and beneficial in patients with good renal function, and they cancel each other out," says Dr. Spence, the author of "How to Prevent Your Stroke." The authors also contend most of the trials did not use a high enough dose of vitamin B12.

NEW YORK | Wed Dec 21, 2011 4:16pm EST

NEW YORK (Reuters Health) - Neither antidepressants nor "talk therapy" were able to outperform inactive placebo pills in a new clinical trial on depression treatment -- though there were hints that the effects varied based on people's sex and race, researchers report.

The findings, published in the Journal of Clinical Psychiatry, add to evidence that people receiving "real" depression treatment in studies -- from antidepressants to St. John's wort -- often do no better than people given a placebo.

A recent review found that a minority of antidepressant users even fared worse than placebo users.

In this latest study, researchers randomly assigned 156 depression patients to either take the antidepressant sertraline (Zoloft and other brands) daily for 16 weeks; undergo a form of psychotherapy called supportive-expressive therapy (twice a week for four weeks, then weekly for 12 weeks); or be in a placebo group given inactive pills.

After 16 weeks, there were no overall differences in how the three groups fared.

Of antidepressant patients, 31 percent were treatment "responders" (meaning they'd fallen below a certain score on a standard measure of depression symptoms, or had seen their score drop at least 50 percent.)

The same was true of about 28 percent of patients in the talk-therapy group, and 24 percent in the placebo group. The differences among the three groups were so small as to be likely due to chance.

"I was surprised by the results. They weren't what I'd expected," said lead researcher Jacques P. Barber, dean of the Institute of Advanced Psychological Studies at Adelphi University in Garden City, New York.

Still, he stressed in an interview, the lack of benefit over placebo does not mean that depression therapies are pointless.

For one, Barber said, receiving a placebo in a clinical trial "is not the same as getting no treatment."

Study participants in placebo groups have contact with health professionals who are asking about their symptoms and well-being, Barber pointed out. And for some people, that attention can make a difference -- and may help explain the placebo response seen in studies.

In addition, at least some people in placebo groups believe they are getting the real treatment. And some studies have suggested that people's beliefs about their therapy play a key role in whether they get better.

But apart from that, different people may respond differently to a given type of depression therapy. Barber's team found some evidence of that.

The study, which focused on urban, low-income adults with major depression, had an unusually large minority population for a clinical trial on depression: Of the 156 patients, 45 percent were African American.

And Barber's team found that African-American men tended to improve more quickly with talk therapy than with medication or placebo.

In contrast, white men fared best on placebo, while black women showed no differences in their responses to the three treatments.

Only white women, Barber said, showed the expected pattern: a quicker response to both medication and talk therapy than to the placebo.

But all of that is based on fairly small numbers of people, and more research is needed to see if the gender and racial differences are real, according to Barber.

A psychiatrist not involved in the study agreed. "Those findings are interesting, but need to be interpreted with a grain of salt," said Dr. David Mischoulon, an associate professor of psychiatry at Harvard Medical School.


As for the overall lack of benefit from the real treatments over placebo -- in this and other studies -- Mischoulon cautioned against reading that as "nothing works for depression."

"I think it's the opposite," he told Reuters Health, "It's more that, everything seems to work to some degree."

Like Barber, Mischoulon said that the placebo condition in clinical trials is not really "no treatment."

His advice for people suffering from depression symptoms is to talk with your doctor about the pros and cons of all the treatment options, including different forms of talk therapy and medication.

"I try to offer as broad a menu of options as possible, because all may potentially help," said Mischoulon, who has also studied alternative depression remedies, like fish oil and acupuncture.

Another caveat from the current study, he noted, is that it looked only at two types of medication. (Some patients were switched to another drug, venlafaxine (Effexor), if they did not respond to sertraline after eight weeks). And it tested just one type of talk therapy.

Supportive-expressive therapy is a short-term form of psychoanalysis that aims to help people understand how their personal relationships are related to their symptoms.

It's different from cognitive behavioral therapy, the best-studied form of talk therapy for depression. Both Barber and Mischoulon said it's not clear if the current findings would extend to psychotherapies other than supportive-expressive therapy.

"This is one type of psychotherapy, and it's two antidepressants," Mischoulon said. "It would be wrong to conclude that psychotherapy doesn't work, and antidepressants don't work."

The study was funded by the National Institutes of Health. Some of Barber's co-researchers have received funding from the pharmaceutical industry.

SOURCE: Journal of Clinical Psychiatry, online November 29, 2011.

What you can do in thirty minutes per day to improve your health

A Doctor-Professor answers the old question "What is the single best thing we can do for our health" in a completely new way.

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