Wednesday, August 17, 2011

Hepatitis News Ticker 8-17; Guide to Clinical Trials for People With Hepatitis C

Treatment Action Group publishes Guide to Clinical Trials for People With Hepatitis C
There are many new hepatitis C drugs being studied in clinical trials. People with hepatitis C have many options to choose from. Whether you have hepatitis C or another medical condition, deciding to participate in a clinical trial can be complicated. Having more information can help you decide whether or not to participate in a clinical trial, and which trial, or trials, may be right for you.

Multiple ascending dose study of BMS-790052, an NS5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1 -
Download the PDF here or visit NATAP for full Text
Hepatology Aug 2011 accepted articles
The current treatment of chronic hepatitis C virus (HCV) infection, a regimen of pegylated interferon alpha (PEG-IFN)-2a or -2b, and ribavirin (RBV) remains unsatisfactory, particularly in the large number of patients with HCV genotype 1 infection whose sustained viral response rates are currently ~40% (1). However, treatment for HCV infection is rapidly evolving with the introduction of direct-acting antiviral (DAA) agents

Utilization of Surveillance for Hepatocellular Carcinoma Among Hepatitis C Virus-Infected Veterans in the United States: 'HCC surveillance low among cirrhotics despite recommendations for HCC surveillance in these high-risk patients' -

Download the PDF here or visit NATAP for full text
Current practice guidelines recommend screening for hepatocellular carcinoma (HCC) in patients with cirrhosis. The evaluation of data in a Veterans Affairs database showed that routine, annual screening for HCC with either serum α-fetoprotein measurement or abdominal ultrasonography was done in only 12% of veterans with cirrhosis. Testing was done inconsistently in 58.5% and not at all in 29.5% of patients with cirrhosis. This study could not determine whether missing screening was due to physicians' failure to recommend tests or patients' failure to adhere to testing. Efforts are needed to improve screening for HCC in at-risk patients."

Global epidemiology of hep B and hep C in people who inject drugs
Improved and more complete data and reporting are needed to estimate the scale of hep B and hep C in people who inject drugs, reports this week's issue of The Lancet.

Injecting drug use is an important risk factor for transmission of viral hepatitis, but detailed, transparent estimates of the scale of the issue do not exist.

Professor Louisa Degenhardt and colleagues from Australia estimated national, regional, and global prevalence and population size for hepatitis C virus and hepatitis B virus in injecting drug users.

The research team systematically searched for data for hepatitis B virus and hepatitis C virus in injecting drug users in peer-reviewed databases, grey literature, conference abstracts, and online resources, and made a widely distributed call for additional data.
From 4386 peer-reviewed and 1019 grey literature sources, the research team reviewed 1125 sources in full.

An estimated 6.4 million injecting drug users are anti-hep B antibody positive

The researchers extracted studies into a customized database and graded them according to their methods.

The team included serological reports of hepatitis C virus antibodies, hepatitis B virus antibodies, or hepatitis B virus surface antigen in studies of injecting drug users with more than 40 participants, and sampling frames that did not exclude participants on the basis of age or sex.
With endorsed decision rules, the team calculated prevalence estimates with anti-hepatitis C virus and anti-hepatitis B antibodies as proxies for exposure and hepatitis B surface antigen as proxy for current infection.

The researchers combined these estimates with injecting drug users population sizes to calculate the number of injecting drug users with positive hepatitis B virus or hepatitis C virus statuses.
The team located eligible reports with data for prevalence of anti-hepatitis C virus in injecting drug users for 77 countries, midpoint prevalence estimates suggested 60—80% of injecting drug users had anti-hepatitis C virus in 25 countries, and more than 80% of injecting drug users did so in 12 countries.
The team found that about 10 million injecting drug users worldwide might be anti-hepatitis C virus positive.

China, USA, and Russia had the largest such populations.
The researchers identified eligible Hepatitis B surface antigen reports for 59 countries, with midpoint prevalence estimates of 5% to 10% in 21 countries, and more than 10% in 10 countries.
Worldwide, the team estimated 6.4 million injecting drug users are anti-hepatitis B antibody positive, and 1.2 million are Hepatitis B surface antigen positive.
More injecting drug users have anti-hepatitis C virus than HIV infection, and viral hepatitis poses a key challenge to public health.

Variation in the coverage and quality of existing research creates uncertainty around estimates.
Professor Degenhardt's team concludes, "Improved and more complete data and reporting are needed to estimate the scale of the issue, which will inform efforts to prevent and treat hepatitis C virus and Hepatitis B virus in injecting drug users."
Lancet 2011: 378(9791): 571-583
17 August 2011

Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity
Potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.

L. Bachmetov1, M. Gal-Tanamy1, A. Shapira2, M. Vorobeychik1, T. Giterman-Galam1,
P. Sathiyamoorthy3, A. Golan-Goldhirsh4, I. Benhar2, R. Tur-Kaspa1,5, R. Zemel1

Article first published online: 16 AUG 2011
DOI: 10.1111/j.1365-2893.2011.01507.x

Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection.

In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication.

A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious virus production in the HCV infectious cell culture system (HCVcc), as analysed by the focus-forming unit reduction assay and HCV RNA real-time PCR.

The inhibitory effect of quercetin was also obtained when using a model system in which NS3 engineered substrates were introduced in NS3-expressing cells, providing evidence that inhibition in vivo could be directed to the NS3 and do not involve other HCV proteins.

Our work demonstrates that quercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.

Hepatitis B

Long-Term Efficacy of Entecavir in People with HBV
Long-term entecavir monotherapy leads to a virological response in a large majority of nucleoside/nucleotide analog-naive patients, even those who still have detectable HBV DNA at 48 weeks.

Healthy You

A Chemically Sound Reason to Exercise with HCV
August 16, 2011
One of the biochemical consequences of physical activity helps those with Hepatitis C maintain their liver's health.
by Nicole Cutler, L.Ac.
We've all heard it before - the key to longevity is eating right and exercising. This sentiment has been repeated so many times that its meaning doesn't seem to carry much weight anymore. Since lifestyle choices can be extremely influential on the progression of chronic Hepatitis C infection, people with this virus are especially likely to receive advice on nutrition and exercise. Instead of allowing food and activity advice to get lost into a repetitive fog, a new perspective on one of these elements may inspire a renewed commitment to liver health.

New risk score spots patients at high risk of serious blood clots
Contact: Emma Dickinson
BMJ-British Medical Journal
Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: Prospective cohort study
A new risk prediction tool can identify patients at high risk of serious blood clots (known as venous thromboembolism) who might need preventative treatment, says a study published on today.

The tool, which can be found at, is based on simple variables which the patient is likely to know and could be easily integrated into GP computer systems to assess patients' risk prior to hospital admission, long haul flights, or starting medications that carry an increased clotting risk.

Venous thromboembolism is a common potentially lethal disease which can be prevented. In England alone, it claims over 25,000 lives each year and, of those who survive, almost a third experience long term effects.
In 2010, the National Institute for Health and Clinical Excellence (NICE) issued guidance to encourage the identification of high risk patients and effective use of preventative measures. Yet there are no validated risk prevention algorithms suitable for use in primary care.
So researchers from the University of Nottingham set out to develop and validate a new clinical risk prediction algorithm (QThrombosis) designed to predict a person's risk of developing a potentially fatal clot.

Using data from 563 general practices in England and Wales, they studied over 3.5 million patients aged 25 to 84 years with no previous history of blood clots. First cases of venous thromboembolism (either deep vein thrombosis or pulmonary embolism) were identified from a patient's medical record or death certificate at one and five years.
The rate of venous thromboembolism was around 15 cases per 10,000 person years of observations.

They show that the risk of venous thromboembolism in both men and women increased with increasing age, body mass index and quantity of cigarettes smoked each day. Risks were also elevated among those with varicose veins, congestive heart failure, chronic kidney disease, chronic lung disease, inflammatory bowel disease, and any cancer.

Admission to hospital in the last six months also conferred a greater risk, as did taking antipsychotic drugs, oral contraceptives, HRT or tamoxifen.

The authors conclude: "We have developed and validated a new risk prediction model which identifies patients at high risk of venous thromboembolism. The algorithm is based on simple clinical variables which the patient is likely to know or which are routinely recorded in GP computer systems. The algorithm could be integrated into GP computer systems and used to risk assess patients prior to hospital admission or prior to the initiation of medication which might increase risk of venous thromboembolism."

They add: "Further research is needed to assess how best to use the algorithm and whether, upon implementation, it has any impact on health outcomes."

What is thrombosis?
A clot within a blood vessel is called a thrombus and the process by which it forms is known as thrombosis. It can be damaging as it might block the flow of blood. Also,part of the clot mite break away and block a blood vessel further along,cutting off the blood supply to important organs.

Zinc lozenges may shorten common cold duration
Depending on the total dosage of zinc and the composition of lozenges, zinc lozenges may shorten the duration of common cold episodes by up to 40%, says Dr. Harri Hemila from the University of Helsinki.

For treating the common cold, zinc lozenges are dissolved slowly in the mouth. Interest in zinc lozenges started in the early 1980s from the serendipitous observation that a cold of a young girl with leukemia rapidly disappeared when she dissolved a therapeutic zinc tablet in her mouth instead of swallowing it. Since then over a dozen studies have been carried out to find out whether zinc lozenges are effective, but the results of those studies have diverged.

Dr. Harri Hemila of the University of Helsinki, Finland, carried out a meta-analysis of all the placebo-controlled trials that have examined the effect of zinc lozenges on natural common cold infections. Of the 13 trial comparisons identified, five used a total daily zinc dose of less than 75 mg and uniformly those five comparisons found no effect of zinc. Three trials used zinc acetate in daily doses of over 75 mg, with the average indicating a 42% reduction in the duration of colds. Five trials used zinc salts other than acetate in daily doses of over 75 mg, with the average indicating a 20% decrease in the duration of colds.

In several studies, zinc lozenges caused adverse effects, such as bad taste, but there is no evidence that zinc lozenges might cause long term harm. Furthermore, in the most recent trial on zinc acetate lozenges, there were no significant differences between the zinc and placebo groups in the occurrence of adverse effects although the daily dose of zinc was 92 mg. Dr. Hemila concluded that "since a large proportion of trial participants have remained without adverse effects, zinc lozenges might be useful for them as a treatment option for the common cold."


More to Addiction than Substance Abuse, Group Says
By Kristina Fiore, Staff Writer, MedPage Today
Published: August 16, 2011
Addiction is a chronic brain disorder that should be treated like any other chronic disease, according to a new definition from the American Society of Addiction Medicine.
In a public policy statement, the group emphasized that neurological mechanisms -- disruptions in neurotransmission, interruptions in the reward system, failure of inhibitory control -- are the key drivers of addiction.

"At its core, addiction isn't just a social problem or a moral problem or a criminal problem," ASAM past president Michael Miller, MD, said in a prepared release. "It's a brain problem whose behaviors manifest in all these other areas."

The statement describes addiction as a primary disease and not the result of other emotional or psychiatric problems. Addiction hijacks the brain's reward system, which involves areas of memory and emotion, and stifles areas of executive functioning, such as impulse control, the statement says.

And genetic factors account for half of the likelihood that a patient will develop addiction.
Given the physiology, addiction should be monitored and managed over time to diminish the risk of relapse, sustain remission, and optimize patient functioning, the group statement continues.

"Many chronic diseases require behavioral choices, such as people with heart disease choosing to eat healthier or begin exercising, in addition to medical or surgical interventions," Miller said in the release. "We have to stop moralizing, blaming, controlling, or smirking at the person with the disease of addiction, and start creating opportunities for individuals and families to get help and providing assistance in choosing proper treatment."

Treatment should involve not only pharmacological management, but psychosocial rehabilitation as well, the policy statement said.

Focus on the neurological underpinnings of behavioral disorders has increased in recent years, the result of advances in brain imaging and neuroscience, the society authors wrote.
Earlier this month, for instance, some dietitians suggested emphasizing the neurology of obesity in order to help patients lose weight more effectively, instead of telling them simply to eat less.
The ASAM policy statement was the result of a four-year process involving more than 80 experts and "extensive dialogue" with the National Institute on Drug Abuse.
The new definition marks the first time ASAM has taken an official position that addiction is not solely related to substance use.


Mum's fears after Isaac, 7, hurt by needle
Full story
A LYNN youngster's search for insects with his young friend turned into a nightmare when he was accidentally pierced by a bloodied and used syringe needle they came across near a makeshift drug den

Liver of no return
Full story
Hepatitis B is a silent killer because many carriers are unaware they even have it.

For Your Reading Pleasure

Grand Rounds is a weekly summary of the best health blog posts on the Internet. Each week a different blogger takes turns hosting Grand Rounds, and summarizing the best submissions for the week.

This Week Hosted By; Dr. Pullen
I think I learned my lesson this time. The first two times I hosted Grand Rounds many of the posts seemed to come from happy bloggers. I think the lesson this time is don’t be a host when all the news is bad. Maybe it’s the drought and heat wave in much of the U.S. Or maybe using the words of Bill Clinton “It’s the economy, Stupid.” For whatever the reason this week’s Grand Rounds is dominated by rants and whines from bloggers around the globe.

A Few Submissions, read all entries here

Dr Schumann at Glass Hospital posts a very cogent and helpful discussion entitled Generics where he explains why most physicians and patients prefer them. He also tells about some of the issues occasionally encountered. One of the few quick reads on this grand rounds and well worth the while.

Now for my not-too-extensive search of the world of bloggers to find some posts to make us all leave smiling. Let’s Start with a doctor having fun writing. At The Examining Room of Doctor Charles you can always find great writing, and usually find a reason to smile

At his blog Septicemia, Prenab goes on a self-labeled rant about the proposal of the British Medical Journal to have a blanket ban on articles by authors with potential industrial conflicts of interest. This has been a hot topic recently as the FDA has taken heat for proposing to allowg input from the pharmaceutical industry in considering new drug releases. I enjoyed reading Why the BMJ should Not Follow NEJU Author Ban.

Read all entries here

Off The Cuff

A Round-up of the Latest Important and Intriguing Malpractice News
From Medscape Business of Medicine > Legal and Malpractice Corner

Reducing Diagnostic Testing Isn't Rationing, Says ACP Vice President
Medical liability expenses are far from the only thing driving up US healthcare costs. Another culprit is "diagnostic testing run amok," according to an op-ed in the Philadelphia Inquirer by Steven Weinberger, MD, CEO and EVP of the American College of Physicians (ACP).[2]

Dr. Weinberger cites some estimates that suggest that excessive testing "costs $200 billion to $250 billion a year, or about 10% of US healthcare expenditures." In Medicare alone, the volume of imaging studies and other tests per . . . beneficiary [since 200] has risen by about 85 percent."
What accounts for all the MRIs, CT scans, ultrasounds, and other diagnostic tests? Patient expectations are 1 factor; other factors include a lack of testing guidelines for many clinical problems and "a lack of physician awareness about the guidelines that do exist." Doctors also test defensively, out of "fear of malpractice litigation," Dr. Weinberger notes.

But much of this testing "raises costs without improving care." To illustrate, Dr. Weinberger points to diagnostic testing for lower-back pain. Much of this turns out to be of little value, he says, since patients with lower-back pain "tend to get substantially better in a few days with exercise and medication." For this reason, ACP "recommends that imaging studies be reserved for those who have serious symptoms or are candidates for invasive interventions."
Does all this smack of rationing? No, says Dr. Weinberger: "Rationing means withholding care that is likely to improve patients' health. In contrast, avoiding overuse or misuse of diagnostic testing is rational and appropriate, because it eliminates care that increases costs but doesn't improve health."
Continue Reading....
**free registration required

More evidence links pesticides, diabetes
By Amy Norton
NEW YORK Wed Aug 17, 2011 2:15pm EDT
(Reuters Health) - People with relatively high levels of certain pesticides in their blood may have an increased risk of type 2 diabetes -- particularly if they are overweight, a new study suggests.

The study, reported in the journal Diabetes Care, is not the first to link chemical pollutants to diabetes.

A number of studies have found a connection between diabetes risk and exposure to older pesticides known as organochlorines, PCBs and other chemicals that fall into the category of "persistent organic pollutants."

Organochlorines are now banned or restricted in the U.S. and other developed countries, after research linked them to cancer and other potential health risks. PCBs, which were once used in everything from appliances to fluorescent lighting to insecticides, were banned in the 1970s.

However, as the name suggests, persistent organic pollutants remain in the environment for years and build up in animal and human body fat.

In the U.S., diet is the main potential source of exposure, according to the Centers for Disease Control and Prevention (CDC) -- with fatty foods, like dairy products and oily fish, topping the list.

Lab research has suggested that some persistent organic pollutants impair the body's ability to regulate blood sugar, which could help explain the link to type 2 diabetes.

Some of the compounds also have been shown to promote obesity, which is itself a major risk factor for diabetes, noted Riikka Airaksinen of Finland's National Institute for Health and Welfare, who led the new study.

For the study, Airaksinen's team measured blood levels of several persistent organic pollutants in about 2,000 older adults.

Just over 15 percent had type 2 diabetes. The risk was higher, the researchers found, among people with the highest levels of organochlorine pesticides.

Those with levels in the top 10 percent were about twice as likely to have diabetes as their counterparts in the bottom 10 percent.

But the link appeared to be limited to people who were overweight or obese.

That, the researchers write, suggests that the pollutants and body fat "may have a synergistic effect on the risk of type 2 diabetes."

The results alone do not prove that organochlorine pesticides were the reason for the higher diabetes risk, Airaksinen told Reuters Health in an email.

The researchers accounted for participants' age, sex, waist size and blood pressure levels. But they had no information on things like diet and exercise habits -- which might help explain the pesticide-diabetes link.

But the overall body of research, according to Airaksinen, is pointing toward a cause-and-effect relationship.

The findings are "highly concordant" with past studies on persistent organic pollutants and diabetes risk, agreed Dr. David R. Jacobs, a professor of epidemiology at the University of Minnesota in Minneapolis who has worked on some of that research.

"I fear that the association of chlorinated persistent organic pollutants with diabetes is causal," Jacobs, who was not involved in the current study, told Reuters Health in an email.

"There is a large scientific background of cell-based and animal research that shows that these compounds disrupt endocrine (hormonal) function," he noted.

And unlike the current study, which was done at one time-point, some others have found that people's levels of persistent organic pollutants predict their odds of developing diabetes in the future, Jacobs said.

Experts say that one way to limit your exposure to the chemicals is to limit the animal fat in your diet.

The fat in fish like salmon and tuna, however, is considered generally healthy.

"In Finland," Airaksinen noted, "we have studied a group of professional fishermen who consume a lot of fish in their diet, and have found that their mortality from various common diseases is actually lower than the general Finnish population. This suggests that the health benefit from eating fish surpasses the potential health risks."

Though most persistent organic pollutants have been long banned, Jacobs said, "they are generally all around us in fatty tissues of living organisms." Those chemicals are released in various ways, he said, and are being constantly recycled.

Pesticides and other industrial chemicals in use now are safer, in the sense of not being persistent, Jacobs said.

"But," he added, "a chemical that is bad for the health of one life form -- say insects and weeds -- is not likely to be good for humans. We need much better and more thorough safety testing for substances that we use in industry and for pest control."

SOURCE: Diabetes Care

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