Showing posts with label Adherence to therapy. Show all posts
Showing posts with label Adherence to therapy. Show all posts

Thursday, September 29, 2011

Hepatitis C patients likely to falter in adherence to treatment regimen over time

Hepatitis C patients likely to falter in adherence to treatment regimen over time, Penn study shows

(PHILADELPHIA) – Patients being treated for chronic hepatitis C become less likely to take their medications over time, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Since the study also showed better response to the drugs when they're taken correctly, the researchers say the findings should prompt clinicians to assess patients for barriers to medication adherence throughout their treatment, and develop strategies to help them stay on track. The study is published online this month in Annals of Internal Medicine.

"Our findings are particularly timely since many chronic hepatitis C patients are now being prescribed direct-acting antiviral drugs, which have a complex dosing regimen that may be even harder for patients to maintain than the two-drug standard therapy," said lead author Vincent Lo Re, MD, MSCE, an assistant professor of Infectious Disease and Epidemiology. "These data show us that we need to develop and test interventions to help patients be more successful at taking their medicine and have the best chance at being cured."

Literacy issues, financial hurdles, and socioeconomic problems such as unstable living situations can all hamper patients' abilities to properly maintain their drug regimen. The authors suggest that refilling patients' pill boxes for them, creating easy-to-follow dosing and refill schedules, and helping them set alarms to remind them to take their medicine may all help improve adherence.

The Penn researchers studied 5,706 chronic hepatitis C patients who had been prescribed the standard treatment for the virus -- pegylated interferon (given as a single weekly shot) and ribavirin (a twice-daily oral medicine) -- using pharmacy refill data and test results for virologic response during treatment. They found that patients who refilled their prescriptions on time had a higher likelihood of being cured of the infection. However, over the course of patients' treatment, adherence waned, and more often for ribavarin. That pattern, Lo Re notes, is similar to that among patients taking drugs for other chronic conditions, during which patients often develop so-called "pill fatigue."

The newer, more powerful direct-acting antiviral drugs, which must be taken every 8 hours, will add to the complexity, and cost, of chronic hepatitis C treatment. In addition, if the newer direct-acting antiviral drugs aren't taken properly, the hepatitis C virus may become resistant to treatment, compromising the chance of cure. Hepatitis C is a communicable disease spread via blood, from needle-sharing during IV drug use, tattooing or piercing, or even from more casual contact like sharing razors and toothbrushes. Worldwide, approximately 180 million people have the disease, about 4 million of them in the United States.

Monitoring for and treating drug-related side effects may also be a key factor in boosting adherence, Lo Re says. The study results showed that patients who received medication for thyroid dysfunction, anemia, or low white blood cell counts – common side effects associated with hepatitis C drugs – were more likely to remain adherent to their antiviral therapy. Although those drugs added more steps into their self care, Lo Re said the resulting relief for symptoms, including depression, fatigue and irritability, and more frequent visits to health care providers typically required with administration of these drugs, may play a role in patients' ability to maintain the regimen overall.

"We know that a major barrier to adherence is side effects of these drugs. People don't feel good when they're on them," he said. "If we can identify those problems and treat them when they occur, patients may be more motivated and feel well enough to continue with their prescribed regimen."

###

The study was funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Department of Veterans Affairs.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

http://www.eurekalert.org/pub_releases/2011-09/uops-hcp092911.php

Monday, September 19, 2011

Monday HCV News Ticker;Patient Adherence to Hepatitis C Treatment

Handmade oil painting reproduction of Reading the News, one of the most famous James Tissot paintings.

Patient Preferences and Assessment of Likely Adherence to Hepatitis C Virus Treatment
Brett Hauber; A. F. Mohamed; C. Beam; J. Medjedovic; J. Mauskopf
Authors and Disclosures
Posted: 09/19/2011; J Viral Hepat. 2011;18(9):619-627. © 2011 Blackwell Publishing

Discussion Only
See Full Text @ Medscape
The results of this study indicate that sustained viral response was the most important attribute of a drug treatment to patients. However, the results of the choice-format conjoint survey also indicate that patients were willing to accept decreases in the probability of achieving sustained viral response to reduce side effects of treatment. Alopecia was the least important of the side effects included in this analysis, while depression and days with flu-like symptoms were relatively more important to patients. The extent to which treatment interferes with work was also an important consideration for patients. In addition, both patient characteristics (prior treatment experience) and treatment attributes (the number of days with flu-like symptoms) affected patients' ratings of likely adherence.

Using adaptive conjoint analysis, Fraenkel et al. [30] also found that treatment benefit (measured as virus eradication in 45% of patients with no cirrhosis after 10 or more years) was the most important HCV treatment attribute among treatment-naïve patients, whereas fatigue, depression and flu-like illness had similar but smaller influences on subjects' preferences. However, patients with moderate or severe fibrosis placed a greater importance on treatment benefit and less on treatment-related side effects than patients with mild or no fibrosis. Significant differences between our study and Fraenkel et al. [30] are that we included different treatment attributes and both treatment-naïve and treatment-experienced patients.

There have been several nonconjoint studies published on HCV patients' preferences.[31–34] Two studies looked at patients' role in decision-making regarding initiating treatment.[31,32] Fraenkel[31] concluded that physicians need to determine patients' levels of uncertainty in decision-making, whereas Tinè[32] reported that chronic HCV patients defer to their physicians in initiating treatment. Schackman et al. [33] found that treatment-naïve patients were more concerned about side effects than physicians and nurses using standard gamble. Witkos et al. [34] examined claims data of Canadian HCV patients and concluded that disease severity, age, HIV status and province of residence increased the likelihood of receiving treatment.

One of the strength of this study is in the use of a choice-format conjoint survey that reflects the attributes of current drug treatments for chronic HCV infection based on published literature and eight face-to-face subject pretest interviews. The results from well-designed choice-format conjoint analyses in health economics have been shown to provide useful information about the relative importance of different treatment attributes to patients and physicians.[24,35,36] Another strength of the study is the use of an innovative method to estimate the likely impact of different medication attributes on adherence. This method provides quantitative estimates that can be used to predict adherence to new medications that have different attributes from current medications.[37,38] Although the impact of patient characteristics and treatment attributes on patients' adherence ratings was estimated in our study using hypothetical scenarios, the results of this study are consistent with previously published results that indicate that nonadherence is owing to treatment-related adverse events for 75% of patients with poor adherence.[6] Because our estimation method gave results that were consistent with observed determinants of adherence to treatment for chronic HCV infection, these estimates could be used in economic models of the cost-effectiveness of a new treatment regimen compared to current treatments. Adherence could be included in these models in an attempt to convert the efficacy results seen in clinical trials to effectiveness in 'real-world' practice.

While choice-format conjoint analysis methods are widely used in health economics to elicit preferences for treatment features and outcomes, they have limitations. One inherent limitation is that subjects evaluate hypothetical treatments. These constructed choice questions are intended to simulate possible clinical decisions but do not have the same clinical, financial and emotional consequences of actual decisions. Thus, differences can arise between stated and actual choices. We have attempted to minimize such potential differences by offering alternatives that mimic real-world trade-offs as closely as possible. In addition, some health professionals are skeptical that people have sufficient understanding of treatment information to competently evaluate treatment alternatives. Diagnosis among subjects in this study was self-reported and not confirmed by physician consultation or chart review. However, we believe the likelihood is small that people without HCV would be likely to complete a study such as this because the study is cognitively challenging and requires an investment in time in exchange for little personal gain. Finally, we recruited subjects through an Internet-based chronic illness panel which means that the sample used in this study is not necessarily representative of the people with HCV in the United States.

Because the treatment alternatives that patients considered and the patients' adherence ratings are based on hypothetical treatment scenarios, the adherence results presented in this study should not be construed as an absolute prediction of the rate of nonadherence to treatment. First, there likely is some underlying rate of nonadherence that is not explained by patient characteristics (prior treatment experience) or treatment attributes (days of flu-like symptoms). Therefore, our estimate of predicted adherence to treatment based on these adherence ratings must, at a minimum, be interpreted as the relative effect of known patient or treatment characteristics on adherence. In addition, a previous study found that self-reported adherence was greater than measured adherence in this patient population indicating that patients underestimated their own rate of nonadherence or were unwilling to acknowledge the level of their nonadherence.[5] If this is the case, the adherence estimates from this study may represent a lower bound on the impact of the number of days of flu-like symptoms on nonadherence. In summary, the results of our analyses have shown that, although efficacy is clearly the most important treatment attribute, other attributes related to treatment side effects are also important and may reduce adherence to current treatments. Because adherence to therapy, especially in those with genotype 1 HCV infections, has been shown to be important for achieving a sustained viral response, new treatment regimens that reduce side effects relative to current treatments might result in higher adherence rates and better clinical effectiveness.
Continue Reading..

Inhibitex Commences Dosing of Phase 2 Clinical Trial of INX-189 in HCV Infected Genotype 2/3 Patients
Phase 1b Extension Trial in HCV-Infected Genotype 1 Patients to Evaluate Higher Doses of INX-189 Also Initiated
September 19, 2011 07:27 AM Eastern Daylight Time
ATLANTA--(EON: Enhanced Online News)--Inhibitex, Inc. (Nasdaq: INHX), announced today that it has recently commenced dosing in a 90-patient randomized, placebo controlled, treatment guided, Phase 2 clinical trial to evaluate the safety, tolerability and antiviral activity of INX-189 in combination with pegylated interferon and ribavirin in chronic HCV-infected genotype 2 and 3 treatment naïve patients. The trial is designed to evaluate three once-daily doses of INX-189 (25 mg, 50 mg and 100 mg) administered in combination with pegylated interferon and ribavirin for 12 weeks, and also includes a control arm in which patients will receive placebo and standard of care treatment (a combination of pegylated interferon and ribavirin for 24 weeks). Each INX-189 combination treatment cohort in the trial will include 25 patients, and the control arm will include 15 patients.

Patients in the INX-189 containing treatment arms that achieve an extended rapid viral response, or eRVR, defined as having HCV RNA below the level of detection after 28 days and 12 weeks of dosing, will stop all therapy after 12 weeks. Those patients who do not achieve an eRVR will continue receiving pegylated interferon and ribavirin for 12 additional weeks.

The Company also announced the initiation of an additional clinical trial of INX-189 designed to evaluate higher doses of INX-189 administered as monotherapy or in combination with ribavirin for seven days. The first cohort in this expanded Phase 1b trial will receive 200 mg INX-189 once daily as monotherapy. Other planned cohorts include 100 mg INX-189 twice daily as monotherapy, 100 mg INX-189 once daily in combination with ribavirin, and possibly higher monotherapy doses of INX-189. Each treatment cohort in the trial will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo.

About HCV and INX-189
Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer, and is the leading cause of liver transplants in the United States.
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2’-C-methyl guanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.

About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company’s clinical-stage pipeline currently includes two Phase 2 development programs; INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections and FV-100, a nucleoside analogue in development for the treatment of shingles-associated pain. The Company also has other HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM® protein platform to Pfizer for the development of a staphylococcal vaccine, which is currently being evaluated in a Phase 1/2 clinical trial. For additional information about the Company, please visit http://www.inhibitex.com/ .

Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the number of patients the Company expects to enroll in the ongoing Phase 2 trial and the planned cohorts, and possibly including higher monotherapy doses of INX-189, in the ongoing supplementary Phase 1b trial, and the Company’s belief that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk of the Company, the FDA, a data safety monitoring board, an institutional review board (IRB), delaying, limiting, suspending or terminating the clinical development of INX-189 at any time for a lack of safety, tolerability, biologic activity or efficacy, commercial viability, regulatory issues, or any other reason and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2010 and its Quarterly Reports on Form 10-Q for the quarters ended March 31 and June 30, 2011. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.

There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex® and MSCRAMM® are registered trademarks of Inhibitex, Inc.

Contacts
Inhibitex
Russell H. Plumb, 678-746-1136
Chief Executive Officer
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, 646-378-2922
CFA
lstern@troutgroup.com

(Ivanhoe Newswire)--- According to the CDC, Hepatitis C is the most common chronic blood borne infection in the United States affecting more than 3.2 million people. But, a new drug has been found to significantly increase the cure rates for those infected.

Hepatitis C virus (HCV) is a disease that can cause severe liver damage, joint pain and even damage to the nervous system and brain. HCV genotype 1 is the most common form of the virus and also the most difficult to treat. In a recent study researchers discovered adding a new drug, telaprevir, to the current combination of treatment has been effective in improving cure rates to almost 80%.

The new study involved a group of 540 patients in which some were treated for a total of 24 weeks with a combination of the drugs pegylated interferon, ribavirin and telaprevir for 12 weeks and pegylated interferon and ribavirin only, for an additional 12 weeks. Other patients in the study were treated for a total of 48 weeks with the 3-drug combination.

Researchers found that many of the patients were able to stop treatment after 24 weeks and had undetectable levels of HCV.

“Vertex conducted a study to determine the optimal duration of treatment in this group who had excellent early response. If viral levels were undetectable from weeks four to 12 with the 3-drug combination, patients were randomized to receive pegylated interferon and ribavirin for an additional 12 weeks (total duration 24 weeks) or for an additional 36 weeks (total duration 48 weeks). This study convincingly showed that there was no advantage in this group with the longer duration. Current guideline is to stop all treatment in this group at 24 weeks,” Dr. Paul Thuluvath told Ivanhoe. Medical Director of the Institute for Digestive Health & Liver Disease at Mercy Medical Center in Baltimore, Maryland, who has been involved in the research regarding the new class of drugs used to treat HCV.

These new findings have made researchers hopeful that the duration of treatment for Hepatitis C can be shortened even further for patients suffering from this disease.

“Future developments in this field will include oral medications without interferon injections and probably even shortened durations of treatment. The progress in HCV treatment has been remarkable in the past five years and we expect continued progress in the management of the ‘silent epidemic’ of HCV that causes considerable morbidity and mortality from liver failure and liver cancer,” Dr. Thuluvath told Ivanhoe.
SOURCE: The New England Journal of Medicine, September 15, 2011. And Centers for Disease Control (www. cdc.gov )

In Case You Missed It
 
NEW YORK | Wed Sep 14, 2011
NEW YORK (Reuters) - The head of infectious diseases at Merck & Co said the company's future all-oral treatments for hepatitis C and its experimental drug for infections with clostridium difficile bacteria could transform treatment and reap big sales.

Merck and biotechnology company Vertex Pharmaceuticals Inc earlier this year introduced rival new oral treatments for hepatitis C that work by blocking the protein protease. But they both must be taken with an injectable interferon that prolongs treatment and causes flu-like side effects.

Roger Pomerantz, who was named head of Merck's infectious disease segment last year, estimated the highly effective new hepatitis C drugs target only about 10 million to 15 million people in developed countries and some emerging markets.

By contrast, he said a newer all-oral treatment regimen that eliminates interferon could target as many as 180 million patients globally, including those in remote and rural regions of Africa and South America.

"We're at just the tip of the iceberg" with current treatments, he said in an interview on Wednesday. "The big change will be when we can provide a simple, compact all-oral regimen."

"Hepatitis C is arguably the largest market opportunity in infectious diseases in my lifetime because of the sheer numbers and the fact that we can cure it," said Pomerantz, who headed Johnson & Johnson's infectious disease division before being hired away by Merck.

Pomerantz said the company also has high hopes for a new way of fighting clostridium difficile (c. difficile), bacteria which are spread in hospitals and are most dangerous for the elderly and others with weakened immune systems.

The sometimes-deadly infections occur in patients who have been treated with broad-spectrum antibiotics that kill off "friendly" bacteria in the gut, allowing clostridium difficile to take root and prosper there. They cause colitis, including attacks of diarrhea and fever that can recur and are not well-controlled by current treatments.

"Over the past five years there has been a new hyper-virulent strain that is more deadly than the usual c. difficile, so we have a perfect storm" situation, Pomerantz said.

Merck's treatment reduced the rate of recurring attacks by more than 70 percent in mid-stage trials, Pomerantz said.

The company hopes to launch the new drug in 2013 or 2014, Pomerantz said. It is a combination of two monoclonal antibodies that block toxins produced by c. difficile.
(Reporting by Ransdell Pierson, editing by Bernard Orr and Matthew Lewis)

Despite the fact that hepatitis C virus (HCV) persists chronically in about 80 percent of those infected, some liver cells remain free of the virus even after many years. Now Sung Key Jang of Pohang University of Science and Technology, South Korea, et al. explain that paradox. During chronic HCV infection, a cellular protein, HMGB1, helps restrain viral reproduction. That prevents HCV from sweeping the liver, and results in a lower blood burden of virus than in the case of hepatitis B. This first description of HMGB1-related responses triggered by HCV infection is published in the September 2011 issue of the Journal of Virology.

The researchers show further that HCV-infected cells secrete HMGB1 proteins into the extracellular milieu. There, these proteins trigger a receptor on the cytoplasmic membrane, called TLR4, causing both an interferon response, which fights the virus, and an inflammatory response.

Two different responses coming from the same receptor at the same time is a common phenomenon. But that can make designing drugs all the more complicated. Boosting the interferon response could vanquish the virus, but the inflammatory response would be harmful. However, Jang says that it might be possible to get the one response without the other. If HMGB1 in the TLR4 receptor is like a hand that fits nicely in a glove, thus triggering both responses, perhaps a drug could be fashioned which could fit a piece of the receptor, like two fingers in a glove, thus triggering only the interferon response. This is an unpublished hypothesis, says Jang, but one that his group is working on.

In the paper, the researchers note that HMGB1 is a "danger" signal. The Danger model of immunology, derived by Polly Matzinger of the National Institute of Allergy and Infectious Disease, NIH, posits that immune responses are initiated by signals from damaged cells. Rather than distinguishing between "self" and "nonself," as per conventional wisdom, the Danger model suggests that when cells are stressed, injured, or killed (by external forces rather than through so-called programmed cell death), they give off alarm signals that activate the immune system to clear the damaging agents.

About 18 million people worldwide are infected with HCV. That virus causes inflammation (hepatitis), massive death of liver cells (cirrhosis), and hepatocellular carcinoma. Liver cancer, primarily hepatocellular carcinoma, which is also caused by heptatitis B virus, is the third leading cause of cancer deaths worldwide, and the ninth leading cause of cancer deaths in the United States, according to Morbidity and Mortality Weekly Report.

(J. Ha Jung, J. Hoon Park, M. Hyeok Jee, S. Ju Keum, M.-S. Cho, S. Kew Yoon, and S. Key Jang, 2011. Hepatitis C virus infection is blocked by HMGB1 released from virus-infected cells. J. Virol. 85:9359-9368.)
Provided by American Society for Microbiology

AUTHORS: Carrie McAdam-Marx, Lisa J. McGarry, Christopher A. Hane, Joseph Biskupiak, Baris Deniz, Diana I. Brixner

SUMMARY: BACKGROUND:
Approximately 3.2-3.9 million U.S. residents are infected with the hepatitis C virus (HCV). Total annual costs (direct and indirect) in the United States for HCV were estimated to be $5.46 billion in 1997, and direct medical costs have been predicted to increase to $10.7 billion for the 10-year period from 2010 through 2019, due in part to the increasing number of HCV patients developing advanced liver disease (AdvLD).


OBJECTIVE: To quantify in a sample of commercially insured enrollees (a) total per patient per year (PPPY) all-cause costs to the payer, overall and by the stage of liver disease, for patients diagnosed with HCV; and (b) incremental all-cause costs for patients diagnosed with HCV relative to a matched non-HCV cohort.


METHODS: This retrospective, matched cohort study included patients aged at least 18 years and with at least 6 months of continuous enrollment in a large managed care organization (MCO) claims database from July 1, 2001, through March 31, 2010. Patients with a diagnosis of HCV (ICD-9-CM codes 070.54, 070.70) were identified and stratified into those with and without AdvLD, defined as decompensated cirrhosis (ICD-9-CM codes 070.44, 070.71, 348.3x, 456.0, 456.1, 456.2x, 572.2, 572.3, 572.4, 782.4, 789.59); hepatocellular carcinoma (HCC, ICD-9-CM code 155); or liver transplant (ICD-9-CM codes V42.7, 50.5 or CPT codes 47135, 47136). For patients without AdvLD, the index date was the first HCV diagnosis date observed at least 6 months after the first enrollment date, and at least 6 months of continuous enrollment after the index date were required.

HCV patients without AdvLD were stratified into those with and without compensated cirrhosis (ICD-9-CM codes 571.2, 571.5, 571.6).

For patients with AdvLD, the index date was the date of the first AdvLD diagnosis observed at least 6 months after the first enrollment date, and at least 1 day of enrollment after the index date was required. Cases were matched in an approximate 1:10 ratio to comparison patients without an HCV diagnosis or AdvLD diagnosis who met all other inclusion criteria based on gender, age, hospital referral region state, pre-index health care costs, alcoholism, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and a modified Charlson Comorbidity Index.

For the HCV and comparison patient cohorts, PPPY all-cause costs to the payer were calculated as total allowed charges summed across all patients divided by total patient-days of follow-up for the cohort, multiplied by 365, inflation-normalized to 2009 dollars. Because the calculation of PPPY cost generated a single value for each cohort, bootstrapping was used to generate descriptive statistics. Incremental PPPY costs for HCV patients relative to non-HCV patients were calculated as between-group differences in PPPY costs. T-tests for independent samples were used to compare costs between case and comparison cohorts.


RESULTS: A total of 34,597 patients diagnosed with HCV, 78.0% with HCV without AdvLD, 4.4% with compensated cirrhosis, 12.3% with decompensated cirrhosis, 2.8% with HCC, and 2.6% with liver transplant, were matched to 330,435 comparison patients.

Mean (SD) age of all HCV cases was 49.9 (8.5) years; 61.7% were male. Incremental mean (SD) PPPY costs in 2009 dollars for all HCV patients relative to comparison patients were $ 9,681 ($176) PPPY. Incremental PPPY costs were $5,870 ($157) and $5,330 ($491) for HCV patients without liver disease and with compensated cirrhosis, respectively. Incremental PPPY costs for patients with AdvLD were $27,845 ($ 965) for decompensated cirrhosis, $43,671 ($2,588) for HCC, and $ 93,609 ($4,482) for transplant. Incremental prescription drug costs, including the cost of antiviral drugs, were $2,739 ($37) for HCV patients overall, $2,659 ($41) for HCV without liver involvement, and $3,102 ($157) for HCV with compensated cirrhosis. These between-group differ- ences were statistically significant at P < 0.001.


CONCLUSIONS: Based on a retrospective analysis of data from a large, MCO claims database, patients diagnosed with HCV had annual all-cause medical costs that were almost twice as high as those of enrollees without a diagnosis of HCV. Health care costs increased dramatically with AdvLD. Data from this study may help MCOs project future HCV costs and facilitate planning for HCV patient management efforts.

A new study has found that HIV-infected men who have unprotected sex with other men (MSM) are at increased risk for contacting hepatitis C virus (HCV) through sex.
HCV transmission primarily occurs through exposure to blood, and persons who inject drugs at greatest risk.

But when Mount Sinai researchers observed a large increase in the number of new cases of HCV transmission among HIV-infected men who did not inject drugs, they took a closer look to examine the role of sexual transmission among these men.

The researchers identified 74 HIV-infected men between October 2005 and December 2010 who had documented new HCV infection and yet reported no other risk factor for HCV infection, including injection drug use.

And they found that the men who had recently contracted HCV were 23 times more likely to have had unprotected anal sex with men.

In addition, HCV genetic analysis suggested that HCV was transmitted within social networks of these men, consistent with the presence of a city-wide epidemic.
"While hepatitis C is rarely transmitted among stable heterosexual couples, this is clearly not the case among HIV-infected MSM in New York City," said Dr. Daniel Fierer, Assistant Professor of Medicine and Infectious Diseases at Mount Sinai School of Medicine.
"MSM, and to some extent their health care providers are generally not aware that having unprotected receptive sex can result in HCV infection.

"The good news is that the cure rate for new HCV infections is very high with early treatment, but without regular testing of the men at risk, these largely asymptomatic infections may be missed and this opportunity lost," he added.
The results of the study are published in the latest edition of the CDC's Morbidity and Mortality Weekly Report.

Stem Cells

South Korea Sets Sights on Becoming Stem Cell Powerhouse
South Korea's president vowed on Monday a series of regulatory reforms to help regain its place as a stem cell research powerhouse, trying to reclaim momentum five years after a cloning scandal.

President Lee Myung-bak said that by breathing new life into the industry, it could become "core new growth engine" for Asia's fourth biggest economy along the same lines as its lucrative IT sector.

"Just a decade ago, Korea took the lead in stem cell research in the world along with the United States," Lee said in a bi-weekly radio address.

"Unfortunately, there was a disappointing incident, which caused inevitable damage to the entire stem-cell research community in Korea," Lee said, referring to the scandal involving the pre-eminent scientist, Hwang Woo-suk.

South Korea had once been considered a global leader in human embryonic stem cell research until review boards said in 2005 that the team led by Hwang had manipulated key data in its studies on cloning stem cells, sparking a fraud case that shook the global scientific community.

As a result of the scandal, South Korea all but put stem cell research into the deep freeze.

Lee said the lapse had allowed other countries such as the United States, Japan, Britain and China to get the jump on South Korea, depriving the country of valuable revenue.

"While we were faltering in our quest for stem cell research, other nations streamlined their regulations and aggressively expanded their investments in research," he said.
"CORE GROWTH ENGINE"

Lee said the government would invest nearly 100 billion won ($90 million) in stem cell research next year and that it would reform related regulations to make clinical and licensing procedures easier.

He said the reforms would help the Korea Food and Drug Administration (KFDA) and other agencies "to ensure that they proactively adapt to the changes in the international environment".

"The government has decided to foster the stem cell industry as a core new growth engine following the footsteps of the IT industry," he said.

Stem cells are the body's master cells and the source of all cells and tissues. Because of their ability to generate different types of cells and multiply and self-renew, scientists hope to harness them to treat a variety of diseases and disorders, including cancer and diabetes, and injuries.

Stem cell research is "very rewarding and significant in that it can give hope to those who suffer from rare and intractable diseases," Lee said.

"In addition, from a business perspective, it can be said to be a high-value-added industry.
"This field is new and offers infinite room for advancement, and how well we manage at this initial stage will make an enormous difference down the road. The country should now set its eyes on emerging as a stem cell powerhouse."

The government will create a national stem cell bank for use to produce, preserve and supply stem cells to various researchers in the country on a stable basis, Lee added.

In July, the KFDA approved stem cell medication in the form of a treatment for heart attack victims for the world's first clinical use.

That Hearticellgram-AMI treatment, developed by FCB-Pharmicell, signaled the country's first salvo to put research in the field back on the frontline.

Healthy You

The study showed that blueberries may have the potential to reduce a variety of risk factors for metabolic syndrome and cardiovascular disease. Phytochemicals - a type of naturally-occurring antioxidants - are thought to be responsible for the health benefits of blueberries as reported by diabeticlive.com .
Tampa, FL (PRWEB) September 19, 2011

Blueberry Consumption Associated with Reduced Risk of Metabolic Syndrome: Fruits have long been recommended as part of a healthy diet, along with vegetables. Aside from providing a healthy, natural boost of energy that is free of the processing and refining that strips nutrition from many of our foods, they contain a variety of compounds and nutrients that afford long-term health benefits. Researchers at the University of Michigan Cardiovascular Center recently conducted a study on blueberries to determine their effect on illnesses such as cardiovascular disease and metabolic syndrome as reported by diabeticlive.com.

The research team at the Cardiovascular Center used rats with a strong predisposition to obesity and diabetes for the study. The rats were divided into two groups; one group was fed a high-fat diet along with blueberry powder, while the other group was fed a low-fat diet with blueberry powder. A control group was fed no blueberries.

The study showed that blueberries may have the potential to reduce a variety of risk factors for metabolic syndrome and cardiovascular disease. Phytochemicals - a type of naturally-occurring antioxidants - are thought to be responsible for the health benefits of blueberries.

The researchers used freeze-dried blueberries crushed into powder since the rats would not likely have eaten full blueberries. The powder was then mixed in with the rats' other food; the blueberry mixture accounted for 2% of the rats' total diet.

The reduction in risk of metabolic syndrome is an important implication for diabetes. Metabolic syndrome is a series of health problems that, when occurring together, increase risk of cardiovascular disease and diabetes. Among the risk factors for metabolic syndrome are raised triglycerides, increased waist circumference (obesity), reduced HDL cholesterol, and increased blood pressure. The blueberry supplements given to the rats in the study appeared to reduce the risk of metabolic syndrome.

The rats had less abdominal fat, lower cholesterol levels, improved insulin sensitivity and fasting glucose, and lower triglyceride levels. They also showed reduced liver size; an enlarged liver is associated with obesity and insulin resistance.

E. Mitchell Seymour, M.S., was the lead researcher on the study. Seymour offered insight as to the mechanism powering the health benefits of the blueberries: "We found by looking at fat muscle tissue, that blueberry intake affected genes related to fat-burning and storage. Looking at muscle tissue, we saw altered genes related to glucose uptake."

According to Steven Bolling, M.D., head of the Cardioprotection Laboratory and heart surgeon at the University of Michigan, "The benefits of eating fruits and vegetables has been well-researched, but our findings in regard to blueberries shows the naturally occurring chemicals they contain, such as anthocyanins, show promise in mitigating these health conditions."

A Bout of Exercise May be the Cure
Article is published in the American Journal of Physiology—
Regulatory, Integrative, and Comparative Physiology

Bethesda, Md. (Sept. 16, 2011)—Researchers have long known that regular exercise increases the number of organelles called mitochondria in muscle cells. Since mitochondria are responsible for generating energy, this numerical boost is thought to underlie many of the positive physical effects of exercise, such as increased strength or endurance. Exercise also has a number of positive mental effects, such as relieving depression and improving memory. However, the mechanism behind these mental effects has been unclear. In a new study in mice, researchers at the University of South Carolina have discovered that regular exercise also increases mitochondrial numbers in brain cells, a potential cause for exercise’s beneficial mental effects.

Their article is entitled "Exercise Training Increases Mitochondrial Biogenesis in the Brain." It appears in the Articles in PresS section of the American Journal of Physiology – Regulatory, Integrative, and Comparative Physiology, published by the American Physiological Society.

Methodology
The researchers assigned mice to either an exercise group, which ran on an inclined treadmill six days a week for an hour, or to a sedentary group, which was exposed to the same sounds and handling as the exercise group but remained in their cages during the exercise period. After eight weeks, researchers examined brain and muscle tissue from some of the mice in each group to test for signs of increases in mitochondria. Additionally, some of the mice from each group performed a "run to fatigue" test to assess their endurance after the eight-week period.

Results
Confirming previous studies, the results showed that mice in the exercise group had increased mitochondria in their muscle tissue compared to mice in the sedentary group. However, the researchers also found that the exercising mice also showed several positive markers of mitochondria increase in the brain, including a rise in the expression of genes for proxisome proliferator-activated receptor-g coactivator 1-alpha, silent information regulator T1, and citrate synthase, all regulators for mitochondrial biogenesis; and mitochondrial DNA. These results correlate well with the animals’ increased fitness. Overall, mice in the exercise group increased their run to fatigue times from about 74 minutes to about 126 minutes. No change was seen for the sedentary mice.

Importance of the Findings
These findings suggest that exercise training increases the number of mitochondria in the brain much like it increases mitochondria in muscles. The study authors note that this increase in brain mitochondria may play a role in boosting exercise endurance by making the brain more resistant to fatigue, which can affect physical performance. They also suggest that this boost in brain mitochondria could have clinical implications for mental disorders, making exercise a potential treatment for psychiatric disorders, genetic disorders, and neurodegenerative diseases.

"These findings could lead to the enhancement of athletic performance through reduced mental and physical fatigue, as well as to the expanded use of exercise as a therapeutic option to attenuate the negative effects of aging, and the treatment and/or prevention of neurological diseases," the authors say.

Study Team
The study was conducted by Jennifer L. Steiner, E. Angela Murphy, Jamie L. McClellan, Martin D. Carmichael, and J. Mark Davis, all of the University of South Carolina.

Investigators tout trial successes for hep C, influenza drugs at ICAAC
While Sangamo was making waves with its news on Carl June's latest gene therapy study, two other developers were reporting successes with their experimental treatments at ICAAC.

Bristol-Myers Squibb ($BMS) reported that its experimental hepatitis C treatment--MS-790052--effectively cured 83% of patients after 24 weeks of therapy. BMS's Douglas Manion, vice president of development and virology, told Bloomberg that "the new standard of care should be 60% to 80% cure rates."
That program is now headed into late stage studies. Leerink Swann has estimated peak sales at $125 million. BMS has four programs ongoing for hepatitis C, a hot field that has attracted considerable attention with the marketing success of Vertex's Incivek......

Pharmaceutical

Summer is ending and that means we can look forward to the flu season. But reaching for the Tylenol is no longer a sure thing, since the venerable pain reliever remains largely out of stock. This is due, of course, to ongoing manufacturing difficulties that Johnson & Johnson has had for nearly two years thanks to bottles that smelled musty, contained too much active ingredients or metallic specks, among other things............

Lynne Taylor
The over-prescribing of medicines in Europe is becoming "chronic," especially among elderly patients, a leading health policy expert has claimed.

A study by Salzburg Medical University has found that prescriptions issued to patients with an average age of 82 were unnecessary in 36% of cases, while for 30% the drugs they were being given were inappropriate, according to Guenther Leiner, president of leading health policy conference the European Health Forum Gastein (EHFG)........

FYI

The FDA called the report "irresponsible and misleading" and another TV doc, ABC's Richard Besser, MD, accused Oz of fear-mongering
 

Friday, September 2, 2011

TGI Friday HCV News:Adherence to Treatment for Hepatitis C

Name: Morning News Artist Jack Vettriano

New On The Blog


Hepatitis C in Minority Populations
Trial Supports Addition of Telaprevir for HCV Genotype 2
Early TIPS for Ascites Study Seeks to Improve Survival

New On The Web Site
Study Suggests HCC Resection Superior to Transplant
Hepatitis C; Type II Cryoglobulinemia
Two New Videos; Posted in Multimedia

Todays News


From HIV and Hepatitis

What Factors Influence Adherence to Treatment for Hepatitis C?
Efficacy, or likelihood of achieving sustained virological response, was the most important factor influencing adherence among people considering treatment for chronic hepatitis C, according to a recent survey.
Increasing rates of non-adherence over time suggest that achieving SVR may not be the only important treatment factor taken into account by people with HCV. Skipping doses may indicate that patients are willing to reduce the likelihood of achieving sustained response in order to avoid treatment side effects.

September 2011 HCV Advocate Newsletter

In This Issue:
NYC: Sexual Transmission of HCV Among HIV Positive Men
Alan Franciscus, Editor-in-Chief
Important Updates at the HCV Advocate HealthWise: Back at Hepatitis C
Lucinda K. Porter, RN
Disability & Benefits: Medicare—Getting the Most Out of It
Jacques Chamber, CLU
HCV Snapshots
Lucinda K. Porter, RN
Clinical Trials
Alan Franciscus, Editor-in-Chief

Dendritic Cells in Liver Protect Against Acetaminophen Toxicity
Released: 9/1/2011 4:10 PM EDT
Source: New York University Langone Medical Center
Newswise —
NYU School of Medicine researchers have discovered that dendritic cells in the liver have a protective role against the toxicity of acetaminophen, the widely used over-the-counter pain reliever and fever reducer for adults and children. The study’s findings are published in the September issue of the journal Hepatology.

The liver is the organ that plays a central role in transforming and filtering chemicals from the body. High-doses of acetaminophen can cause hepatotoxicity, chemical driven liver damage. In fact, accidental and intentional acetaminophen overdose are the most frequent causes of acute liver failure (ALF) in the United States. Acetaminophen related liver failure by intentional or accidental overdose causes 56,000 emergency room visits, 2,600 hospital visits and 450 deaths annually. As a result, this year the FDA mandated drug manufacturers to start limiting the amount of acetaminophen in combination drug products and is currently exploring adding safer dosing instructions to children’s acetaminophen products.

In the new study, researchers found an abundance of dendritic cells in the liver can protect the organ from acetaminophen damage while low levels of dendritic cells in the liver are associated with exacerbated liver damage, liver cell and tissue death, known as centrilobular hepatic necrosis, and acute liver failure from acetaminophen.

“Our research results confirm a central role for dendritic cells and their powerful regulation of acetaminophen’s toxicity,” said George Miller, MD, senior author of study and assistant professor, Departments of Surgery and Cell Biology at NYU Langone Medical Center. “High levels of dendritic cells have a novel, critical and innate protective role in acetaminophen hepatotoxicity. We now have greater insight into the liver’s tolerance of acetaminophen toxicity and dendritic cell regulation of these toxins.”

In the study, researchers used acetaminophen-induced hepatic injured mice models to closely examine the protective role of dendritic cells. Dendritic cells are the main antigens in the liver that trigger an immune response and control the liver’s tolerance to high doses of invading toxins like acetaminophen. In the experiment all mice were injected with acetaminophen but some mice models were first depleted of dendritic liver cells using a diphtheria toxin while others had their dendritic cell levels bolstered with Flt3L, a protein in the blood previously shown to increase proliferation of dendritic cell levels.

Researchers discovered dendritic cell depletion exacerbates acetaminophen’s damage to the liver. The acetaminophen treated mice with depleted dendritic cells had more extensive liver cell and tissue death compared to other mice. Also, these mice died within 48 hours of acetaminophen challenge- whereas death was rare in other mice without dendritic cell depletion. In addition, the study shows dendritic cell expansion successfully diminished the hepatotoxic effects of acetaminophen protecting the liver from damage.

“Understanding the regulatory role of dendritic cells is an important step in the development of immune-therapy for acetaminophen induced liver injury,” said Dr. Miller, a member of the NYU Cancer Institute. “Advanced studies are warranted to investigate further the protective role of dendritic cells in humans and their use as a possible new therapeutic target for liver failure prevention in the future.”

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation’s premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world’s first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center’s tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research.
For more information, go to http://www.nyulmc.org/.

Stem Cells

From Nature

Q&A with the new head of the NIH stem cell center
In October 2005, Mahendra Rao shocked the scientific community when he quit his job as head of the US National Institute on Aging’s stem-cell section and announced plans to go into industry.

The $52-million, seven-year center was launched in early 2010 by the agency to develop new therapies using stem cell approaches. With a heightened focus at the NIH on translational medicine, Elie Dolgin spoke to Rao to find out how he plans to turn stem cell discoveries into cell-based therapies.

What sets the regenerative medicine center apart from other academic institutes dedicated to stem cell technologies?

Neither in size nor in scientific quality could one say that this center is any different from some of the other more established centers. However, there are two crucial differences. One, this is a government center, and the government’s mandate is different than that at any other center. So, that’s a really important distinction. The second thing is that the center doesn’t function in isolation. It’s what’s around it that makes it very useful, and what’s around it is a whole lot of infrastructure and investment that’s gone in to building up a way to take things from the bench to the bedside. There are two really important pieces to that in the NIH Chemical Genomics Center and the NIH Clinical Center. Both of them are widely recognized, state of the art, best in class type of centers...... Continue Reading...

Diabetes

Abstract

Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):503-16.
Current understanding of insulin resistance in hepatitis C.
Kaddai V, Negro F.
Source
Department of Pathology and Immunology, Centre Médical Universitaire, Rue Michel-Servet 1, 1205 Geneva, Switzerland.

Abstract
Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences.

Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-α-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.

Related-Diabetes Updates On The Blog
ScienceDaily (Sep. 1, 2011) —
Robert Winkler says he limped around on his painful left foot for six months, suffering unnecessarily from a misdiagnosis by a physician who didn't know about the symptoms and treatments for Charcot foot, a form of localized osteoporosis linked to diabetes that causes the bones to soften and break, often resulting in amputation.

When his primary care physician finally agreed to Mr. Winkler's request for an x-ray, they discovered the metatarsal bones in Mr. Winkler's left foot were all broken -- a common symptom of this serious and potentially limb-threatening lower-extremity complication.
A new article in the September issue of the journal, Diabetes Care, describes Charcot foot and its treatment with a goal of educating medical professionals about this painful inflammation of the foot. The article is the product of an international task force of experts convened by the American Diabetes Association and the American Podiatric Medical Association in January to summarize available evidence on the pathophysiology, natural history, presentations and treatment recommendations for Charcot foot syndrome.

"Even though it was first described in 1883, the diagnosis and successful treatment of Charcot foot continue to be a challenge because this syndrome is not widely known or understood by the broader medical profession," said Lee C. Rogers, D.P.M., co-director of the Amputation Prevent Center at Valley Presbyterian Hospital in Van Nuys, CA, and lead author of the Diabetes Care article. "Charcot foot is now considered to be an inflammatory syndrome most often seen in patients with diabetes which can be successfully treated in its early stages."
The article describes Charcot foot as a condition affecting the bones, joints and soft tissues of the foot and ankle, which is characterized by inflammation in the earliest phase and is associated with diabetes and neuropathy. The report finds offloading, or removing weight from the foot, is the most important initial treatment recommendation. Surgery can be helpful in early stages involving acute fractures of the foot or ankle or in later stages when offloading is ineffective, according to the article.

In Mr. Winkler's case, he was first diagnosed with Charcot foot in 2004 and had already undergone one surgery that relieved the problem for several years. By 2010, though, he was facing the potential amputation of the foot because of complications associated with Charcot foot syndrome.

His podiatrist referred him to Dr. Rogers at Valley Presbyterian Hospital's Amputation Prevention Center, an integrated limb salvage center that is one of only a handful in the nation. Since its December 2009 opening, the Amputation Prevention Center's specialized multidisciplinary team of highly skilled professionals has treated patients from all over the country and around the world with leading-edge technology, achieving a limb salvage rate of 96 percent.

George Andros, M.D., the Center's Medical Director, performed vascular surgery to restore circulation to Mr. Winkler's left foot so that it would heal. Then, Dr. Rogers performed surgery to rebuild the bones in Mr. Winkler's foot. Dr. Rogers also implanted a bone stimulator that acts like a pacemaker for bones which encourages Mr. Winkler's body to rebuild and fuse the broken bones in his left foot. As a result, Mr. Winkler is expected to be able to recover the use of his left foot.

"I'm very pleased because I had gone to another doctor and he wanted to amputate my foot," Mr. Winkler said. "When I found Dr. Rogers and Valley Presbyterian Hospital's Amputation Prevention Center, it's like I found a blessing and an angel in disguise. I have tears running down my face as I describe to you how I will be able to get up out of my chair and walk because of the care I received at Valley Presbyterian Hospital. All the people there are superb. They treat me like a king."

Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Valley Presbyterian Hospital, via EurekAlert!, a service of AAAS.

Journal Reference:
L. C. Rogers, R. G. Frykberg, D. G. Armstrong, A. J. M. Boulton, M. Edmonds, G. H. Van, A. Hartemann, F. Game, W. Jeffcoate, A. Jirkovska, E. Jude, S. Morbach, W. B. Morrison, M. Pinzur, D. Pitocco, L. Sanders, D. K. Wukich, L. Uccioli. The Charcot Foot in Diabetes. Diabetes Care, 2011; 34 (9): 2123 DOI: 10.2337/dc11-0844

Sjogren's

Learn More From Medical News Today;
What Is Sjogren's Syndrome? What Causes Sjogren's Syndrome?
Primary Sjogren's syndrome - experts are not sure what the exact cause of Sjogren's syndrome is. Most believe it is likely to be a combination of environmental and genetic factors. Some people are probably born with certain genes that make them more susceptible to having an abnormal immune system. Sometime during their life, an environmental factor, such as hepatitis C viral infection, or an infection with the Epstein-Barr virus may have triggered the immune system not to work properly.

Challenges in understanding Sjögren's syndrome - improved insights into the pathogenesis generate hope for innovative therapies?
Published:19 August 2011
With this in mind, the authors of these reviews address central questions about the immunopathogenesis of Sjögren syndrome. Sipsas and colleagues [4] explore the potential role of retroviruses in initiating or maintaining disease. Vitali [5] examines the differences and similarities of sicca symptoms and risk of developing lymphoma between patients with HIV or hepatitis C virus infection and those with Sjögren syndrome

From Medpage

Sjogren's Sidelines Venus Williams
By Nancy Walsh, Staff Writer, MedPage Today
Published: September 01, 2011
When former No. 1 women's tennis star Venus Williams withdrew from the U.S. Open this week, she brought immediate attention to the little-known autoimmune disease Sjögren's syndrome, thought to afflict some 0.5% of adults.The disease is characterized by destruction of the exocrine glands, leading to excessive dryness of the mouth and eyes.But Sjögren's syndrome also is associated with symptoms such as debilitating fatigue and musculoskeletal problems that could seriously interfere with athletic performance.

"It's my suspicion that it may have been the systemic manifestations like fatigue and joint pain that have been troubling her and that could be difficult for a person trying to function at that very physically demanding level," Robert Spiera, MD, director of the vasculitis and scleroderma program at the Hospital for Special Surgery in New York City, told MedPage Today. Spiera has not been involved in Williams' treatment.

Earlier in the week Williams, 31, won a match in the tournament, held at the Billie Jean King National Tennis Center in Flushing, N.Y., but when she left the venue, after withdrawing on Wednesday, she said in a statement, "I enjoyed playing my first match here and wish I could continue, but right now I am unable to," according to the New York Times.

Steven Taylor, who heads the Sjögren's Syndrome Foundation, said in a statement, "On behalf of the four million Americans with Sjögren's, we applaud Venus for publicly stepping forward and shedding light on this serious autoimmune disease."

Diagnosing the disease can be challenging, and can involve salivary flow testing, salivary gland biopsy, and blood tests for autoantibodies such as rheumatoid factor, antinuclear antibodies, SSA and SSB antibodies.

Williams, who has been sidelined in recent months because of what was thought to be a viral illness, said she was "thankful to finally have a diagnosis." In fact, according to Taylor, the average time to diagnosis is 6.5 years after symptom onset.

The condition affects women far more than men, as is the case with most autoimmune diseases, and generally begins when patients are in their 40s.
"When patients present with complaints such as fatigue, clinicians need to be proactive and think beyond the common diagnoses like depression and thyroid disorders and ask about dry eyes and mouth," Spiera said.

Some similarities exist between Sjögren's syndrome and other autoimmune disorders such as rheumatoid arthritis and lupus, including articular, renal, and neurologic involvement.
For many patients, symptoms can be managed with products such as eye lubricants.
But for those with more severe manifestations, systemic medications such as anti-inflammatories, antimalarial drugs, and immunosuppressive agents may be needed.
Williams apparently is taking an oral medication that could take several months for its full effects to be seen, according to another report in the Times.

B cells are thought to play a crucial part in the development of Sjögren's syndrome, accumulating and becoming hyperactive in the exocrine glands and heightening immune antigenic responses.
For reasons that are not yet clear but which may involve B-cell proliferation and mutagenicity, in some patients the immune hyperactivity can evolve into a lymphoproliferative malignancy.
"Patients with Sjögren's have a risk of lymphoma that is as much as 40-fold higher than the general population," Spiera said.

Certain features of the disease seem to be associated with the development of lymphoma, such as bulky lymph or parotid gland enlargement, skin vasculitis, and low blood levels of complement.
"But the vast majority of patients with Sjögren's syndrome never develop lymphoma," Spiera said.
"Most patients with the disorder live very productive lives. Sjögren's does affect their quality of life, but there are strategies to help deal with their problems," he added.

Pharmaceuticals

From Reuters
FDA may get two more months to review new drugs
(Reuters) - U.S. regulators and the drug industry want to extend by two months the deadline for the Food and Drug Administration to approve or reject new drugs.
The extended timeline was tucked into the proposed deal the FDA forged with the prescription drug industry on the fees companies pay for drug reviews. The FDA posted the proposal on its website on Thursday.

The FDA said it would need an extra 60-day "filing date" before the clock starts ticking on its 10-month deadline to review new drugs, or six months for a priority review.
The new five-year agreement, which will be put out for public comment, comes as the FDA faces increased criticism from congressional Republicans and the industry for being too slow in approving new products, which they say stifles innovation and job creation.
"People are kind of scratching their heads" over the longer review time, said an industry source familiar with the negotiations on the user fees.

"But the idea is that FDA will use those two months to really prepare for the review ... so the hope is that it gives us more predictability and makes everything shorter in the long-run."
The Prescription Drug User Fee Act (PDUFA), first enacted in 1992, gives the FDA millions of dollars annually to review new products for the U.S. market in exchange for quicker approvals and other promises.

Congress must reauthorize the current PDUFA legislation before it expires in September 2012. The FDA's new fee agreement with industry, which would kick in at the beginning of 2013, would be part of the reauthorization legislation .

MORE FEE FLEXIBILITY
The fees system is controversial, with some critics contending they influence the FDA, which is supposed to protect the health and safety of consumers.
Currently, about a third of the agency's funding comes from makers of drugs and medical devices -- and that could grow if the FDA reaches a final agreement with generic drugmakers.
In 2010, the FDA collected $922 million in user fees out of a total budget of about $3.28 billion. The agreement with the prescription drug industry would increase user fees 6 percent over levels in 2012 for an estimated total of about $713 million in 2013, FDA Commissioner Margaret Hamburg said in Congressional testimony in late July.

The FDA also wants more flexibility on how it spends the money. Some of the fees will go toward drug safety, rare diseases and for training FDA staff in new technologies and science -- part of a broader push to improve the agency's scientific expertise.

"If you look at the original PDUFA, all of that went directly to just review processes," said Ryan Hohman, the director for communications and policy at Friends of Cancer Research, a think-tank and advocacy group.
"But the FDA and industry stepped back and recognized that in the economic environment, they need to have the increase in science or else they won't be able to approve these drugs at a speedy time for patients."

The FDA must still agree on the specifics of its user-fee program with the medical device industry, which started paying fees in 2002. It is also planning a new fee program with makers of generic drugs and 'biosimilars' -- copycat versions of brand-name biotech drugs.
(Editing by Karey Wutkowski and Andre Grenon)

From Pharmalot


By Ed Silverman
September 2nd, 2011
Once again, a web page is deemed problematic by the FDA. In a letter sent by the agency earlier this week, Pfizer was chastised because its Lipitor web page made misleading representations and suggestions about several other drugs. The issue came to light, by the way, thanks to the FDA ‘Bad Ad’ program, which encourages people to file complaints about troublesome promotions (see this)....... Continue Reading..

Cancer Research


Jennerex press release
Jennerex cheered by early efficacy data for cancer-killing virus
A small, mid-stage study of Jennerex's genetically engineered virus offered some important preliminary proof-of-concept data on its ability to zero in on cancer cells with just a single infusion. Reporting in Nature, investigators said biopsies confirmed the virus was replicating inside the tumors of 7 of the 8 people with metastatic cancers who were given the engineered dose, leaving healthy tissue untouched. Researchers noted several weeks after treatment the tumors in half of the group had stopped growing, indicating their cancers may have stabilized, and that in one case tumors appeared to shrink.

Why cancer cells change their appearance?

Like snakes, tumor cells shed their skin. Cancer is not a static disease but during its development the disease accumulates changes to evade natural defenses adapting to new environmental circumstances, protecting against chemotherapy and radiotherapy and invading neighboring organs, eventually causing metastasis.
Fondo de Investigaciones Sanitarias (FIS), Josef Steiner Cancer Research Foundation, Lilly Foundation, European Research Council Advanced Grant, Health Department of the Catalan Government, Instituto de Salud Carlos III, ICREA

F
YI


Comprehensive Management of Liver Disease 
at the Montefiore Einstein Center for Transplantation
Friday, September 02, 2011
“The Marion Bessin Liver Research Center is a highly respected and internationally renowned research facility that performs revolutionary work in the fields of liver transplantation and stem cell research,” says Milan Kinkhabwala, M.D., Surgical Director of the Montefiore Einstein Center for Transplantation, Chief of the Division of Transplantation, Montefiore Medical Center, and professor of surgery, Albert Einstein College of Medicine. “The program needed a clinical arm to help advance the treatment of liver disease and provide direct benefits to patients. We brought together a team of highly trained hepatologists, hepatobiliary surgeons and gastroenterologists, and integrated those clinicians with the existing team of research professionals to create a truly interdisciplinary center featuring both clinical and research expertise that is dedicated to providing innovative, novel treatments for liver disease.”
Physicians are also involved in clinical trials utilizing Telaprevir, a new medication for treatment of viral hepatitis C........

Healthy You


Diet and hep C
Staying as healthy as possible will help you cope better with hep C. To help improve your health, eating a wide variety of food in the right balance is important. The following advice about diet and food has been developed by dietitians who work with hep C. It aims to dispel myths and help you to stay as healthy as possible.
Avoid restrictive or cleansing diets as there is little clinical or biological basis to support them. The bottom line is that if you don’t have serious liver damage (e.g. cirrhosis) there are no particular foods that you should seek or avoid because of your hep C. If you do have serious liver damage, speak to your specialist or doctor for dietary advice...Continue Reading..

The Low-Fat Con?
By Simon Donovan
Published: September 2, 2011
Posted in: Editorial, Nutrition
Products such as mayonnaise, cottage cheese and other dairy products often come in low-fat or reduced fat varieties. But what are reduced or low-fat products? In order for a food or product to be classified as low-fat it must contain fewer than 30% of its total calories from fat, in simple terms the product must be constitute less than 30% fat. Whilst reduced fat products do not have to meet set criteria with regards to their fat content, they must just contain less fat than their natural products. For products such as cheese and mayonnaise to be less than 30% fat requires a significant proportion of the fat to be removed. Common sense tells us that if we take something out we must put something back in to replace it. So what is replacing this fat? Yes, you have guessed, it is sugar..........Continue reading..

Osteoarthritis (OA)


Glucocorticoid treatment may prevent long-term damage to joints
Joint injury can result in irreversible damage of cartilage which, despite treatment and surgery, often eventually leads to osteoarthritis (OA) in later life. New research published in BioMed Central's open access journal Arthritis Research & Therapy demonstrates that short term treatment of damaged cartilage with glucocorticoids can reduce long term degenerative changes and may provide hope for prevention of OA after injury.

A normal joint is covered by a layer of cartilage containing proteoglycans such as aggrecan and lubricating fluid containing glycosaminoglycans (GAG) such as hyaluronic acid. In a double whammy, after injury proteoglycans and other molecules in cartilage begin to break down and the synthesis of these proteoglycans within cartilage is reduced. Additionally proinflammatory cytokines such as TNFα, IL-1β, and IL-6 are released into the synovial fluid after injury and further increase GAG loss from cartilage.

Using a 'worst-case scenario' system in which cartilage was subjected to mechanical injury and bombarded with immune system-stimulating bio-molecules (TNFα and IL-6) the glucocorticoid dexamethasone (DEX) was able to reduce GAG loss and restore proteoglycan synthesis levels to normal.

Prof Alan Grodzinsky from the MIT Center for Biomedical Engineering said, "Glucocorticoid injections are sometimes used to relieve the pain of established osteoarthritis, but there are concerns about long-term use. Our results suggest that short-term glucocorticoid treatment after joint injury may help restore components of cartilage to preinjury levels and consequently may prevent the long term changes which lead to osteoarthritis."

Thursday, April 28, 2011

Hepatitis C Therapy; Adherence to Treatment and Quality of Life


Adherence to Treatment and Quality of Life during Hepatitis C Therapy

A Prospective, Real-life, Observational Study
Patrick Marcellin; Michel Chousterman; Thierry Fontanges; Denis Ouzan; Michel Rotily; Marina Varastet; Jean-Philippe Lang; Pascal Melin; Patrice Cacoub

Abstract and Introduction

Abstract
Background: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C.

Aims: To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence.

Methods: This cohort study included unselected chronic hepatitis C patients initiating peginterferon α-2b plus ribavirin. 100% adherence was defined by taking all the prescribed doses of both drugs for the full initially intended duration, as declared by the patient or believed by the physician. Quality of life was assessed using the short-form health survey (SF-36) questionnaire.
Results: 1860 patients were analysed, including 72% treatment-naive, 36% genotype 2/3, 23% psychiatric, 44% drug addicts and 3% human immunodeficiency virus (HIV)-positive patients. Early treatment discontinuation occurred in 30% of patients. Overall, 38% of patients reported 100% adherence. Patient- and physician-reported adherences were discordant, with a 20–30% overestimation by physicians. HIV co-infection [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.36–4.67], no drug use during follow-up (2.37, 1.30–4.31), genotype 3 (1.55, 1.20–2.00) and treatment-naive (1.32, 1.03–1.69) were associated with 100% adherence. Quality of life worsened during treatment but returned to baseline after the end of treatment.
Conclusions: Imperfect adherence to combination therapy is common in routine patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. Knowledge of these factors might help identify patients who are most in need of intervention and plan more frequent and accurate follow-up.

Introduction
The current standard of care for chronic hepatitis C is the antiviral combination therapy with peginterferon α and ribavirin.[1,2] Peginterferon is administered subcutaneously once a week and ribavirin orally twice daily. Successful treatment, i.e. achievement of a sustained virological response, has been obtained in 79–93% of genotype 2 or 3 hepatitis C virus (HCV) patients after 24 weeks of treatment; as well as in 41–52% of genotype 1 patients and 77% of genotype 4 patients after 48 weeks of treatment in clinical trials.[3–6] Good adherence to treatment is believed to enhance the rate of sustained virological response, as shown in patients from prior trials who received ≥80% of both their total peginterferon and ribavirin doses for ≥80% of the expected duration of therapy.[7] However, adverse effects of interferon-based therapy – mainly flu-like symptoms, neuropsychiatric disorders, anaemia and neutropenia – are significant, justify frequent dose reduction of peginterferon and ribavirin and represent one major cause of premature treatment discontinuation.[8] Shortened antiviral therapy may be considered in some patients depending on genotype, baseline viral load and viral kinetics,[9–11] but only a minority of patients are concerned in routine practice, at least in France.

These data originate from randomised, controlled clinical trials. However, many patients in routine clinical practice are nonresponders or relapsers to previous interferon-based therapy and the majority present with a wide spectrum of comorbidities. In particular, the high prevalence of psychiatric or substance abuse disorders in patients with chronic HCV infection is well known.[12] Conversely, people with chronic psychiatric disorders[13,14] and intravenous drug users[15–17] are far more likely to be infected with HCV compared with the general population. In addition, one-fourth to one-third of human immunodeficiency virus (HIV)-infected patients are co-infected with HCV.[18,19] Besides strict contraindications, such diagnoses have constituted the most common reason patients have been denied treatment for HCV infection, not only in clinical trials[3,4] but also, until recently, in the real life.[20,21]

We performed a cohort study in chronic hepatitis C patients to evaluate the adherence to peginterferon α-2b and ribavirin combination therapy and to identify factors associated with good adherence in a real-life setting. We also assessed the coherence between patient-reported and physician-reported adherence, and the health-related quality of life.

Patients and Methods
This prospective, multicentre, observational study was carried out in University hospitals, non-University hospitals and private practice offices involved in the management of hepatitis C in France. All patients aged ≥18 years with chronic hepatitis C and initiating combination therapy with peginterferon α-2b and ribavirin were proposed to participate in the survey, whether naive for hepatitis C therapy or not. In accordance with the French law, Ethics Committee's approval was not required as the protocol was strictly observational and usual practice was unchanged. However, all patients gave informed consent to participate. Approval of the 'Commission Nationale de l'Informatique et des Libertés' was obtained, ensuring that patient data were kept confidential according to the French regulation.

As for all observational studies, there were no protocol-specific procedures or study visits. Patients saw their physician as per usual practice in the centre. The investigator and the patient completed an anonymous questionnaire each at inclusion, every 3 months during treatment and 6 months after the end of treatment. Patients filled in their questionnaires in the waiting room and either gave it back to the physician in a sealed envelope or returned it using a prepaid envelope.

Physicians recorded the socio-demographical characteristics, history of hepatitis C, selected comorbidities, process of care, concomitant treatments and adverse events. Comorbidities included past and current psychiatric history, HIV or HBsAg positivity, chronic diseases and use of psychoactive products. History of hepatitis C included source and duration of infection, viral load documented by quantitative PCR (Amplicor™, Roche Diagnostics, France), HCV genotype, liver fibrosis and necro-inflammation (Metavir, FibroTest-ActiTest®,[22] Knodell score) and previous antiviral treatment. Process of care included the intended antiviral treatment regimen (drug doses and duration), any subsequent treatment modification (dose modification or treatment discontinuation), the reason for modification and patient's therapeutic education. Patients recorded the antiviral medication actually taken and self-assessed their quality of life using the validated French translation of the MOS 36-item short-form health survey (SF-36) questionnaire.[23] Each SF-36 subscore ranges from 0 (worse) to 100 (best), except health transition, which ranges from 0 (best) to 100 (worse).

Outcomes
At each visit under treatment, patients reported the number of missed peginterferon injections in the past month (the last four injections) or missed ribavirin intakes in the past week (the last 14 intakes). To estimate patient-reported adherence at a given time point, we took into account the 'actual' doses as reported by the patient at each visit and compared it with the most recent physician prescription (thus integrating modifications of prescription that could have occurred over time). To estimate the patient-reported overall adherence, we took into account the adherence estimated at each visit, the actual treatment duration and the treatment duration initially intended by the physician. As a result, patients who declared having taken all the prescribed doses of both products for the full initially intended treatment duration were classified as 100% adherent. Those who declared having taken ≥80% of at least one product for ≥80% of the initially planned duration were classified as ≥80% adherent.

Physician-reported adherence at a given visit and overall was estimated similarly, using the response to the following questions: 'In your opinion, how many times did the patient missed a peginterferon injection in the past month (the last 4 administrations)?' or 'In your opinion, how many times did the patient missed a ribavirin intake in the past week (the last 14 intakes)?'.

Statistical Analysis
Statistical analysis was conducted using sas 8.2 (SAS Institute Inc., Cary, NC, USA). Tests were two-sided and type I error was set at 0.05. Descriptive statistics were performed using all available data. Bivariate group comparisons were carried out using the Kruskal–Wallis, chi-square or Fisher's exact test as appropriate. The relationships between adherence and a set of potential explanatory variables were analysed by forward stepwise logistic regressions. These variables included those for which the groups differed significantly (P<0.05) at baseline in bivariate analyses (100 vs. <100% adherence and/or ≥80 vs. <80% adherence), and variables expected to be related to adherence. The quality of life data were analysed as recommended in the SF-36 manual and interpretation guide.[23]

Results

Patients
A total of 184 investigators enrolled and followed up 2001 HCV patients in the survey between November 2002 and January 2005. Of these patients, 141 were excluded from analysis because they did not receive combination therapy with peginterferon α-2b and ribavirin combination therapy (n=37), duration of combination therapy was not available (n=79) or virological data were not available (n=25). Compared with the analysed population, excluded patients were more often genotype 1 carriers (66 vs. 55%, P=0.013) and less often genotype 3 carriers (185 vs. 25%, P=0.072). They had more severe liver disease (Metavir A2–A3: 66 vs. 54%, P=0.022; F3–F4: 47 vs. 34%, P=0.007), and had received more often a previous HCV treatment (43 vs. 28%, P<0.001). All other baseline data were not significantly different.
The analysed population included 1860 patients. Their baseline characteristics are provided in Table 1. Most of them (72%) were naive for hepatitis C therapy and 36% had genotype 2 or 3 HCV infection. Liver disease was assessed by biopsy in the majority of patients (n=1606, 86%) and estimated using noninvasive markers in the remaining patients. Two-thirds of patients had significant fibrosis (F2, F3, F4: 65%), including 15% of cirrhotics.

Comorbidities were frequent. The cohort included 22% of psychiatric patients, 44% of drug users and 3% of HIV-co-infected patients. Current psychiatric disorders were diagnosed by a psychiatrist in 62% of the cases and included mainly depressive (n=203, 11%), anxiety (n=129, 7%), psychotic (n=19, 1%) and bipolar (n=8, 0.4%) disorders. Other comorbid chronic diseases were hypertension (n=176, 36%), diabetes mellitus (n=107, 22%) and asthma (n=42, 9%). Health-related quality of life was altered, each SF-36 subscore being moderately lower than that in the general population in France.[23]

Antiviral Treatment
The mean dose regimen initially prescribed was 1.37 μg/kg/week (median 1.5, n=1837) for peginterferon α-2b and 922 mg/day (median 1000, n=1820) for ribavirin. A total of 1089 (58.5%) patients received various forms of therapeutic education at the discretion of the physician during the first 3 months of treatment. The average dose of both drugs progressively decreased over time, reaching 0.89 μg/kg/week (median 0.8, n=1729) for peginterferon and 595 mg/day (median 545, n=1728) for ribavirin at month 12. According to the physician, 915/1860 (49%) patients did not complete therapy as intended initially. The main reason for not doing so was virological criteria (n=302, 16%), lost to follow-up (n=244, 13%), safety (n=182, 10%), patient's request (n=78, 4%), another reason (n=51) or not specified (n=58). However, as calculated subsequently, only 563 (30%) patients had 'insufficient' treatment duration, i.e. <80% of the recommended duration (24 weeks with genotype 2 or 3, 48 weeks with the other genotypes). Adverse events were reported in 1598 (86%) patients overall.

Adherence to Treatment
Patient-reported adherence to combination therapy was 100% for the full initially intended treatment duration (overall adherence) in 580/1510 (38%) patients; it was ≥80% in 747 (50%) patients. The proportion of patients with good adherence at a given time point was stable over time, at 53–58% for 100% adherence and 64–66% for ≥80% adherence (Fig. 1).

Proportion of patients with 100% and ≥80% adherence to combination therapy (patient report).


Patient- and physician-reported adherences to treatment were discordant. As shown quarterly in Figure 2, the proportion of patients reporting a 100% adherence to peginterferon at a given time point was 76–79%, whereas physicians believed it was above 97%. Moreover, the proportion of patients reporting a 100% adherence to ribavirin was 62–66%, whereas physicians believed it was above 90%.

Figure 2.
Proportion of patients with 100% adherence to (A) peginterferon α-2b and (B) ribavirin over time, as reported by the patient and as perceived by the physician.

Adherence to ribavirin was always worse than adherence to peginterferon (Fig. 2) and adherence to both products (Fig. 1) was always worse than adherence to ribavirin. Therefore, most patients with imperfect adherence to one product were different from those with imperfect adherence to the other product.
Bivariate comparison of patients who took 100% of both products for the full initially intended treatment duration with those who did not is provided in Table 2. They differed significantly for the following items. 100% adherent patients had longer transport time to the physician office (P=0.001). They were more often genotype 2 or 3 HCV carriers (P=0.009) and naive for antiviral HCV therapy (P=0.037). In addition, they had less frequent diabetes (P=0.026), they consumed lower alcohol amounts at baseline (P=0.023) and they were less often regular drug users (P=0.017), but were more often HIV co-infected (P=0.003). They also used illicit drugs less frequently during follow-up (P=0.007) and, although not significantly, drunk less frequently >20g/day alcohol (P=0.053). They did not differ markedly for the HCV treatment actually received and occurrence of adverse events.

The potential explanatory variables proposed to the multivariate model included genotype, remoteness of the centre (transport time), Metavir activity and fibrosis scores, sex, age, BMI, previous HCV treatment, serum HCV RNA, HIV co-infection, psychiatric disorders (ever and at baseline), diabetes, alcohol consumption >20g/day (at baseline and during follow-up), drug use (at baseline and during follow-up) and therapeutic education. As a result (Table 3), the factors significantly associated with 100% adherence to combination therapy were HIV co-infection, no illicit drug use during follow-up, HCV genotype 3, HCV treatment-naive and, to a lower extent (odds ratio close to 1), remoteness of the centre.

Quality of Life
The change from baseline of SF-36 subscores is displayed in Figure 3. During the treatment period (up to month 12), all physical and mental domains progressively worsened, in particular those reflecting problems at work or in daily activities that result from the physical (role physical) and mental (role emotional) status. The mean change from baseline of the mental and physical composite scores, which integrate all SF-36 domains except health transition, was, respectively, −6.4 and −6.5 points at month 6, and −5.7 and −5.3 points at month 12. The health transition score, which estimates the change of perceived health condition compared with 1 year before, also worsened during treatment as shown by a mean change from baseline at +6.6 points at month 6 and +5.5 points at month 12. After the end of treatment, quality of life was returned above the pretreatment level; the mean change from baseline was +2.6, +2.4 and −6.2 points for the mental composite score, physical composite scores and health transition score respectively.

Figure 3.
Mean change from baseline of SF-36 subscores (point). MCS, mental composite score; PCS, physical composite score. Physical domains: BP, bodily pain; GH, general health; PF, physical functioning; RP, role physical. Mental domains: MH, mental health; RE, role emotional; SF, social functioning; VT, vitality. HT, health transition



Almost all SF-36 domains were significantly worse at baseline in patients who reported an adherence <100% compared with patients with 100% adherence (P<0.05 for PF, BP, GH, VT, SF, MH, PCS and HT; not significant for RP, RE and MCS). During and after treatment, changes of quality of life were parallel in both groups; there were no significant differences between groups for the change from baseline of each SF-36 subscore, whatever the time point.

Discussion
To our knowledge, this is the largest study assessing adherence to HCV therapy using data on dose taking. Imperfect adherence was common. Overall, only 38% of our routine patients reported strict adherence to peginterferon α-2b and ribavirin, i.e. full-dose, persistent therapy as initially intended by the physician. In addition, 76–79% of patients on treatment reported having taken all peginterferon doses in the last 4 weeks; 62–66% reported having taken all ribavirin doses in the last 7 days; and 53–58% reported having taken all doses of both drugs at months 3, 6, 9 and 12. We also provide information on adherence in terms of early treatment discontinuation (30%) and dose decreases, as usually referred to by clinicians in HCV infection.
Our results add to the literature as among the few studies that assessed adherence in terms of dose taking, none did so in the whole population of routine HCV patients and over the whole treatment period. In a clinical trial including 401 mono-infected HCV patients,[24] at least 95% of patients reported having taken all peginterferon doses in the past 4 weeks at months 1, 3, 6, 9 and 12; the rate of patients who reported having taken all ribavirin doses in the past 4 days decreased from 91% at month 1 to 43% at month 12. In a cross-sectional study involving 180 routine HCV patients,[25] 7% of patients reported having missed at least one peginterferon dose in the last 4 weeks and 21% having missed at least one ribavirin dose in the last 7 days. Patients were under treatment since 19.3 ± 13.4 weeks in average. In a retrospective study where adherence was estimated using pharmacy refill data in 188 HCV US Veterans,[26] 73% of patients were found with at least 100% adherence to peginterferon and 68% with at least 100% adherence to ribavirin during the initial 3 months of treatment. Lastly, in a cohort of 63 HCV/HIV-co-infected patients,[27] 23% of patients discontinued treatment early and 98% of those on treatment reported having taken all peginterferon and ribavirin doses in the past 2 weeks at months 3, 6 and 12. Such a high adherence is not surprising as dose-taking adherence is nowadays routinely stressed in HIV patient care.

However, the ability of physicians to recognise nonadherence was poor. Our study physicians markedly overestimated adherence to combination therapy, by 20–30% compared with patient self-report. This phenomenon has already been shown in other chronic diseases such as HIV infection or diabetes but not yet in chronic HCV infection.[28,29] Several reasons exist including for example poor or judgemental provider–patient communication.[30,31] Moreover, in this indication, electronic monitoring has provided much lower rates of adherence than self-reported adherence,[24] suggesting that patients also overestimate adherence to combination therapy. This medication-taking behaviour is also well known in other chronic disorders.[30] Therefore, healthcare providers should be more vigilant about adherence to HCV combination therapy in their daily management, especially in terms of missed ribavirin doses. Indeed, standard ribavirin dosing is complex and ribavirin dose reductions, at least in the first weeks of treatment, may alter virological outcome.[26, 32–34] Patient-related reasons for nonadherence may include forgetfulness, the decision to omit doses, lack of information and emotional factors.[30] Clinician-related reasons may include, in addition to poor communication with the patient, failing to explain the treatment benefits and side effects and not giving consideration to a patient's lifestyle. More flexibility in indication for treatment could have a positive impact on the individual prognosis of patients and the overall control of the disease burden. Although there is no perfect method to assess adherence to medication, patient self-report is probably the simplest and most effective method of measurement.

This study provides other clinically relevant information. Patients who did not present with the following baseline characteristics of HCV infection, HIV co-infection, HCV genotype 3 and HCV treatment-naive, and patients who used illicit drugs during HCV treatment were at higher risk of imperfect adherence. Interestingly, adherence was not associated with history of addiction or psychiatric disorders, suggesting that these conditions should no longer limit access to HCV antiviral therapy. In addition, treating intravenous drug users should have a positive impact on prevention of transmission, with a chance of reducing the incidence of new cases. Knowledge of factors predictive of poor adherence is a useful resource for physicians to help identify patients who are most in need of intervention and plan more frequent and accurate follow-up.
Careful assessment of health-related quality of life was regularly performed in our patients using a validated questionnaire. As expected, quality of life was impaired before treatment initiation compared with the general population[23,35] and both the mental and physical domains worsened during treatment. However, 6 months after the end of treatment, it was returned to baseline, even slightly better than before treatment. Quality of life changes were parallel in patients with perfect and imperfect adherence. These results confirm previous reports of temporary worsening.[36,37] Therefore, physicians should reassure patients and encourage them to persist with therapy despite frequent side effects and worsened quality of life.

In conclusion, this cohort study brings potential clinically relevant information by emphasising the following points. Imperfect adherence to combination therapy with peginterferon plus ribavirin is common in routine chronic hepatitis C patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. These findings suggest that assessment of adherence to HCV combination therapy by physicians should be improved. This could be easily carried out by the wide use of standardised adherence measurement tools such as a self-questionnaire, keeping in mind that patients may overestimate the true figures. The need to enhance communication would be triggered by discordance between the physician and patient assessments. Knowledge of baseline characteristics associated with adherence might help adjust the monitoring in a subset of patients at higher risk of nonadherence.