Showing posts with label Men and HCV. Show all posts
Showing posts with label Men and HCV. Show all posts

Sunday, March 18, 2012

Why men are at higher risk for hepatocellular carcinoma?

Accepted Manuscript
International hepatology

Why men are at higher risk for hepatocellular carcinoma?

Vincent W. Keng, David A. Largaespada, Augusto Villanueva
PII: S0168-8278(12)00211-5
Reference: JHEPAT 4161
To appear in: Journal of Hepatology
Received Date: 28 February 2012
Accepted Date: 5 March 2012

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Why men are at higher risk for hepatocellular carcinoma?
Vincent W. Keng1,2,3, David A. Largaespada1,2,3, Augusto Villanueva4,5,*
1Masonic Cancer Center, 2Department of Genetics, Cell Biology and Development, 3Center for Genome
Engineering, University of Minnesota, Minneapolis 55455, USA. 4HCC Translational Research
Laboratory, Barcelona-Clinic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i
Sunyer (IDIBAPS), Liver Unit, Hospital Clínic, Barcelona, Spain, 5Centro de Investigación Biomédica en
Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Carlos III, Spain.
*Corresponding author. Address: Laboratori de Recerca Translacional d'Oncologia Hepàtica,
BCLC-Group. CIBEREHD. IDIBAPS, Centre Esther Koplowitz. Planta 3, Rosselló, 153. 08036
Barcelona, Spain. Tel.: 93-2279155; fax: 93-2275792
E-mail address: (A. Villanueva

Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Li Z, Tuteja G, Schug
J, Kaestner KH. Cell. 2012 Jan 20;148(1-2):72-83. Copyright (2012). Abstract reprinted with
permission from Elsevier.

Hepatocellular carcinoma (HCC) is sexually dimorphic in both rodents and humans, with significantly higher incidence in males, an effect that is dependent on sex hormones. The molecular mechanisms by which estrogens prevent and androgens promote liver cancer remain unclear. Here, we discover that sexually dimorphic HCC is completely reversed in Foxa1- and Foxa2-deficient mice after diethylnitrosamine-induced hepatocarcinogenesis. Coregulation of target genes by Foxa1/a2 and either the estrogen receptor (ER ) or the androgen receptor (AR) was increased during hepatocarcinogenesis in normal female or male mice, respectively, but was lost in Foxa1/2-deficient mice. Thus, both estrogen-dependent resistance to and androgenmediated facilitation of HCC depend on Foxa1/2. Strikingly, single nucleotide polymorphisms at FOXA2 binding sites reduce binding of both FOXA2 and ER to their targets in human liver and correlate with HCC development in women. Thus, Foxa factors and their targets are central for the sexual dimorphism of HCC.

© European Association for the Study of the Liver. Published by Elsevier B.V. All rights

Despite recent breakthroughs in the management of hepatocellular carcinoma (HCC), it is still the fastest-rising cause of cancer-related death in the United States [1]. Unfortunately, most patients are diagnosed at intermediate-advanced stages, when curative therapies are not a primary option. HCC natural history is fairly well know, since most tumors arise from a traceable underlying liver disease (i.e., cirrhosis), allowing for early diagnosis in the setting of surveillance programs. In patients with cirrhosis, there is a striking gender imbalance in HCC incidence, with a solid predominance for males regardless of geographic area, etiologic factor and ethnicity. Male to female ratio averages between 2:1 to >4:1 across studies [2].

These discrepancies are not merely explained by gender-specific differences in exposure to cirrhosis
risk factors (e.g., viral hepatitis or alcohol abuse), since experimental models of chemically induced HCC also demonstrate a clear male predominance, although molecular mechanism behind gender bias remain unknown. There is also preliminary evidence suggesting that specific genomic profiles, once HCC has developed, are predominant according to patient’s gender, reflected by an enrichment in certain molecular subclasses [3,4].

In a recent study by Li et al. [5], the authors report a central role for the winged helix transcription factors Foxa1/Foxa2 in controlling estrogen and androgen signaling via the recruitment of estrogen receptor alpha (ER ) and androgen receptor (AR) to hepatocyte target genes. They found that the effects of sex hormones in the liver are Foxa1/Foxa2-dependent and provide a novel molecular mechanism responsible for gender dimorphism in HCC. Sexually dimorphic HCC was completely reversed in Foxa1- and Foxa2-deficient mice after chemically induced (diethylnitrosamine) HCC. The authors also included human samples in their analysis, and despite the fact that no mutations in any of the FOXA genes have been reported so far in HCC, the authors provide evidence that certain single nucleotide polymorphisms at FOXA2binding sites reduce its affinity with ER , and this correlates with increased incidence of HCC development in women.

A similar gender bias occurrence was observed in a recent forward genetic screen using the Sleeping Beauty transposon insertional mutagenesis system [6]. Overall, the study by Li et al. [5] reveals a novel interplay between Foxa and hormone receptors binding sites that justifies gender disparities in HCC.
Molecular data indicate that androgens contribute to the HCC development by acting as tumor promoters via induction of DNA damage and oxidative stress [7]. Conversely, estrogens have been suggested to act as general suppressors of HCC through reduction in the proinflammatory effects of MyD88-mediated secretion of IL6 [8]. In addition, estrogens seem to exert different tumorigenic properties depending on the tissue type, since contrary to the epidemiological data in cirrhotic women, chronic exposure to estrogens favors carcinogenesis in breast and uterus.

Paradoxically, both androgens (i.e., anabolic steroids) and estrogens (e.g., oral contraceptives) are able to induce benign liver tumors (i.e., adenomas) and ultimately HCC in individuals without underlying liver disease (Fig. 1). Overall, the effects of estrogens in terms of cancer development are largely tissue and environment dependent, protective in experimental models of cirrhosis but inducing oncogenesis in normal liver, and promoting tumor growth in full-blown HCC. Strikingly, the study by Li et al. [5] found that tumor load in female Foxa deficient mice far exceeded that of control males, suggesting that estrogens could have a pro-tumorigenic effect in the absence of Foxa1/Foxa2. Whether Foxa is the link that explains these opposing effects of estrogens requires further investigation. Background inflammation in cirrhosis could play an additional confounding role, emphasized by the crosstalk between IL6-STAT signaling and estrogens in experimental models of HCC [8].

From a therapeutic standpoint, several studies have tried to evaluate the role of anti-estrogen therapy (e.g., tamoxifen) in patients with overt HCC. Evidence of expression of ER in some tumors and experimental data of estrogen-dependent HCC growth provided the scientific rational for this approach. Most of the studies were small trials, conducted in the 1990s and including a heterogeneous patient population. A meta-analysis including close to 700 patients revealed no impact of tamoxifen in 1-year survival in patients with HCC [9]. Data on anti-androgens or a possible role of hormone therapy in the chemo-preventive scenario are even less informative.

In summary, we are at the beginning of unraveling the complex molecular mechanisms behind gender disparities in HCC. Among them, estrogens seem to play a role in IL6 production and modulation of gene expression through FOXA transcription factors, what prevents HCC development in experimental models of HCC. However, more data are still need to define the implication of sexual hormones in the molecular pathogenesis of HCC. This could provide the proof-of-principle to rescue hormone-based drugs for further evaluation as systemic therapies of HCC in certain clinical contexts.

Conflict of interest
The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

[1] Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M. Cancer Statistics, 2009. CA: A Cancer Journal for
Clinicians. 2009;59:225.
[2] El-Serag HB, Rudolph KL. Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis.
Gastroenterology. 2007;132:2557–2576.
[3] Boyault S, Rickman DS, De Reyniès A, Balabaud C, Rebouissou S, Jeannot E, et al. Transcriptome
classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 2006;45:42–52

Tuesday, March 13, 2012

Higher serum testosterone increases the risk of HCV–related liver disease

Higher serum testosterone increases the risk of HCV–related liver disease

Higher serum testosterone is associated with an increased the risk of hepatitis C–related liver disease in males, reports the most recent of Hepatology.

Males have strikingly increased risk of advanced liver disease.

However, the association between testosterone and risk of hepatitis C virus (HCV)-related advanced liver disease is unknown.

Dr Michael DeBakey and colleagues from Texas, USA performed a cross-sectional study in male veterans with chronic HCV.

Blood samples were obtained to measure total serum testosterone and perform the FibroSURE-ActiTest.

There was a 25% increase in advanced fibrosis risk

The team obtained other risk-factor data through systematic questionnaires, physical measurements, and serological tests.

The researchers evaluated the association between total testosterone and risk of advanced hepatic fibrosis and inflammatory activity measured by the FibroSURE-ActiTest.

A total of 308 eligible study participants were prospectively recruited.

There were 105 cases with advanced fibrosis, and 203 mild fibrosis controls as well as 88 cases with advanced inflammatory activity, and 220 mild activity controls.

The research team found that the mean total serum testosterone was significantly higher in advanced fibrosis cases as well as advanced inflammatory activity cases, compared to mild disease controls.

The research team observed a significant 25% increase in advanced fibrosis risk, and 15% increase in advanced inflammatory activity risk for each 1-ng/mL increase in total serum testosterone.

Total testosterone in the upper tertile was associated with an even greater excess risk of advanced fibrosis than advanced inflammatory activity.

Dr DeBakey's team concludes, "Total serum testosterone is associated with an increased risk of both advanced hepatic fibrosis and advanced hepatic inflammatory activity in HCV-infected men."

"Testosterone may be important in the pathogenesis of HCV-related advanced liver disease in males."

Hepatology 2012: 55(3): 759–768
13 March 2012

Friday, August 26, 2011

HCV News; Higher serum testosterone is assoc w-increased risk of advanced hepatitis C-related liver disease in males

Higher serum testosterone is associated with increased risk of advanced hepatitis C-related liver disease in males
White DL, Tavakoli-Tabasi S, Kuzniarek J, Pascua R, Ramsey DJ, El-Serag HB; Hepatology (Aug 2011)

BACKGROUND: Males have strikingly increased risk of advanced liver disease. However, the association between testosterone and risk of hepatitis C virus (HCV)-related advanced liver disease is unknown.

METHODS: We performed a cross-sectional study in male veterans with chronic HCV. Blood samples were obtained to measure total serum testosterone and perform the FibroSURE-ActiTest. Other risk factor data were obtained through systematic questionnaires (e.g., alcohol), physical measurements (e.g., BMI) and serological tests (e.g., viral load). The association between total testosterone and risk of advanced hepatic fibrosis (F3 and F3/F4) and inflammatory activity (A3 and A2/3) measured by FibroSURE-ActiTest was evaluated with logistic regression.

RESULTS: A total of 308 eligible study participants were prospectively recruited (mean age 57, 52% African-American). There were 105 cases with advanced fibrosis and 203 mild fibrosis controls; and 88 cases with advanced inflammatory activity and 220 mild activity controls. Mean total serum testosterone was significantly higher in advanced fibrosis cases as well as advanced inflammatory activity cases compared to mild disease controls (6.0 ng/ml vs. 5.3 ng/ml and 5.9 ng/ml vs. 5.4 ng/ml, respectively). We observed a significant 27% increase in advanced fibrosis risk and 16% increase in advanced inflammatory activity risk for each 1 ng/ml increase in total serum testosterone. Total testosterone in the upper tertile was associated with an even greater excess risk of advanced fibrosis than advanced inflammatory activity (OR(adjusted advanced fibrosis) =3.78, 95% CI 1.88-7.61 vs. OR(adjusted advanced inflammatory activity) =2.64, 95% CI 1.29-5.45, respectively).

CONCLUSIONS: Total serum testosterone is associated with an increased risk of both advanced hepatic fibrosis and advanced hepatic inflammatory activity in HCV-infected men. Testosterone may be important in the pathogenesis of HCV-related advanced liver disease in males. (HEPATOLOGY 2011.)

New HCV Symposium to Debut at The Liver Meeting® in 2011
By Ann Haran, AASLD Staff
AASLD is excited to debut our new HCV Symposium at The Liver Meeting® 2011. This inaugural symposium Integrating HCV Practice Guidelines and Treatment Advances into Clinical Practice was developed by the Hepatitis C Special Interest Group (SIG) and will be led by moderators Gary L. Davis, MD, Raymond Chung, MD, and John Ward, MD.

The program was designed to educate providers on newly approved and anticipated therapies for HCV and how these therapies should be integrated into clinical practice. As these agents represent a new class of drugs in this field, they will present new challenges for treatment monitoring, side effect management, drug resistance emergence, and personalization of therapy. This program will lay a basic mechanistic foundation upon which to build clinical management guidelines, but the emphasis will be on the latter.

Important emerging issues on public policy and methods of implementation will also be discussed. The symposium will review the updated AASLD Treatment Guidelines for HCV, which will be published prior to The Liver Meeting® 2011. HCV is certain to be a hot topic at The Liver Meeting® with the recent approval of the direct acting antiviral agents (DAA) telaprevir and boceprevir.

Therefore, Dr. Chung and his colleagues encourage those persons involved in the evaluation and management of HCV to attend this symposium, as speakers will discuss not only these two new drug therapies, but will also “provide attendees with a horizon view of the many other exciting developments that are just around the corner for HCV.” This meeting will focus “not just on theory, but also on the practice of implementing the new therapies and understanding both their promise and limitations.”

Dr. Chung expects there to be a great deal of interest in both the therapies themselves and in gaining an understanding of who should be treated and who may justifiably defer therapy. He predicts that, with expansion of DAA classes, “an interferon-free universe will be possible.”Dr. Chung also points out the potential public health benefit of identifying future candidates for these new therapies. ”How do we identify those people so they won’t miss out? With improved treatment efficacy, duration, and tolerability, we don’t want to leave undiagnosed patients at the dock.” No final set of recommendations for who should be screened has been established as yet; this issue will be discussed in Dr. Ron Valdiserri’s presentation on the DHHS Action Plan on Viral Hepatitis.

Dr. Sanjeev Arora will also give an implementation-focused presentation, describing the ECHO Project and its efforts to expand health care to areas with less access to experienced treaters. The symposium will also discuss many of the challenges associated with using the new HCV treatments. As Dr. Chung reminds us, “no therapy comes without its own set of issues.” The challenges involved with using boceprevir and telaprevir include the frequency of dosing, effect of food, potential drug interactions, and new and more stringent stopping rules for virologic failure. Dr. Chung states that the symposium will also consider the role of host genetic tests such as IL28B genotyping, in treatment decision-making.

In addition to Dr. Chung, Dr. Valdiserri, and Dr. Arora, the symposium will include presentations from Hepatitis SIG members Dr. Michael Fried, Dr. Andrew Muir, and Dr. David Nelson, as AASLD’s recently formed Hepatitis C SIG played a key role in developing the new HCV Symposium. Dr. Valdiserri is the Deputy Assistant Secretary for Health, Infectious Diseases, for DHHS, while Dr. Arora was the originator of the ECHO Project. Overall, Dr. Chung hopes the symposium will “convey an understanding of the optimal and rational use of direct antiviral therapies.” Participants will be provided with an opportunity not only to learn how the new therapies are used now, but also to envision how they will be used in the future.
Click here to view the complete program for this exciting new symposium.
The symposium is included as part of the Annual Meeting registration fee. This electronic newsletter is a bi-weekly publication of AASLD and replaces the former bi-monthly print newsletter and weekly e-news. Members are welcome to submit articles and may send suggestions to


From Fierce Biotech

Medivir deals generics biz amid HepC drug trials
August 26, 2011 — 10:45am ET By
Eyeing the prospects of its experimental hepatitis C drug, Swedish biotech Medivir ($MVIR) has sold off the generics unit of its subsidiary BioPhausia to Bluefish Pharmaceuticals. Medivir scooped up BioPhausia in June to tap the Nordic market in case its hepatitis C drug, TMC435, is approved. Medivir offloaded BioPhausia's generics unit, called BMM Pharma, for SEK 26 million ($4.12 million) along with inventories valued at SEK 12 million (or $1.9 million), Genetic Engineering News reports. The transaction comes as Medivir and its partner, Johnson & Johnson's ($JNJ) Tibotec, move full steam in late-stage development of TMC435, which is the top candidate in Medivir's R&D pipeline, according to a release.

The company's first product, a cold sore treatment called Xerese, was launched in the U.S. in February. "This deal is a natural last step in the concentration and focus of BioPhausia's business, which began about a year ago. We will now be focusing on the ongoing commercial development of our proprietary products and parallel imported Products," said Maris Hartmanis, CEO of BioPhausia.

Clearly, Medivir is keeping focused on ushering TMC435, a protease inhibitor, through trials and to potential regulatory approvals for hepatitis C. With the white-hot market for drugs against the liver disease nowadays, that's not a bad bet.
here's the Medivir release- see the coverage in Genetic Engineering News Related Articles: J&J's success with Hep C partners might hit a snag

What Are Biosimilars?
Biosimilars are copycat versions of expensive biotechnology drugs. Although technically these "biosimilars" are not called generic.

Quoted from an article @ Reuters in Jan 2011;"Because of the complexity of biotech drugs, which are produced through biological processes that generally involve recombinant DNA technologies, they are often called "biosimilars" rather than generic copies. Biotech drugs are usually made from living cell lines controlled by different manufacturers, it is impossible for generic companies to make identical copies as they do with simple chemical-based drugs, which do not require fresh clinical trials. Biosimilars of drugs like Amgen's white blood cell-booster Neupogen are already on the market in Europe."

Biosimilars In Todays News;
Biosimilars: physicians cite concerns over supporting data
World News August 26, 2011 Lynne Taylor The majority of US and European physicians are wary of using a biosimilar medicine for an indication for which supporting clinical data are lacking, according to new research. Physicians' attitudes towards "indication extrapolation" - where a biosimilar (generic biologic product) needs only to show similarity in a Phase III study for one indication for the product to be granted approval for other indications for which the original branded product is used - vary from country to country, according to the study, which is published by business information firm Decision Resources. Moreover, the authors found that, out of the specialists which they surveyed, rheumatologists, nephrologists and gastroenterologists in particular told them that indication extrapolation should not be permitted, or should be done carefully, because of minute differences between the biosimilar and the branded original product which might be clinically significant........

From Pharmalot

Hospitals Keep Buying Those Gray Market Meds
The ongoing shortage of many medications is generating not only considerable angst among physicians and politicians, but mushrooming gray market activity, as we have reported previously. And yet another survey reveals that shadowy offers and purchases are on the rise, along with an accompanying rise in price. To be specific, purchasing agents and pharmacists at 549 hospitals were queried by the Institute for Safe Medicine Practices, a non-profit watchdog group, and 56 percent reported receiving daily solicitations from up to 10 different gray market vendors by phone, e-mail and fax. And 52 percent acknowledged by one or more meds from gray market vendors in the last two years. Not surprisingly 80 percent reported such purchases had increased in the last two years as shortages rose..........

FDA: High-Dose Citalopram Tied to Heart Risks
By: DIANA MAHONEY, Internal Medicine News Digital Network
The antidepressant citalopram should not be used at doses greater than 40 mg per day because such doses can lead to prolongation of the QT interval, the Food and Drug Administration announced Aug. 24 in a drug safety communication. Further, the drug should not be prescribed to patients with congenital long QT syndrome, and extra precautions should be taken for patients with other underlying heart conditions, the agency said. Studies do not show a benefit in the treatment of depression at doses of the selective serotonin reuptake inhibitor higher than 40 mg/day. Previously, the citalopram (Celexa) label stated that some patients might require a dose of 60 mg/day.

The agency’s dosage recommendation is based on postmarketing reports of QT prolongation associated with citalopram and results of a randomized, double-blind, placebo-controlled crossover study evaluating the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. The latter study showed that, compared with placebo, the maximum mean prolongations in the individually corrected QT intervals for patients randomized to 20-mg and 60-mg doses of citalopram, respectively, were 8.5 msec and 18.0 msec. The prolongation of the corrected QT interval was estimated to be 12.6 msec, based on the relationship between serum citalopram concentration and QT interval, the FDA statement said. Because such dose-dependent changes in the electrical activity of the heart can lead to abnormal heart rhythms, including the potentially fatal torsades de pointes, and in the absence of evidence demonstrating that citalopram at doses higher than 40 mg/day is beneficial in the treatment of depression, the FDA determined that citalopram should no longer be used at doses above 40 mg/day and that it should never be used in patients with congenital long QT syndrome.

Also, because individuals with underlying heart conditions, such as heart failure or bradyarrhythmias and those predisposed to insufficient serum potassium and magnesium because of comorbid illness or other drugs are at particular risk, the FDA has made the following safety recommendations:

• Correct hypokalemia and hypomagnesemia before administering citalopram and monitor electrolytes as clinically indicated.
• Consider more frequent electrocardiogram monitoring for patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval. • The maximum recommended dose for patients with hepatic impairment, who are older than 60 years, who are CYP 2C19 poor metabolizers, or who are taking cimetidine is 20 mg/day because each of these factors can increase blood levels of citalopram, thus increasing the risk of QT interval prolongation and torsades de points.
• Advise patients to contact a health care professional if they experience signs or symptoms of an abnormal heart rate or rhythm while taking citalopram.

The citalopram drug label has been revised to include the new drug dosage and usage recommendations, and the revised package insert will include information about the potential for QT interval prolongation and torsades de pointes.

Healthy You

Activity Eases RA Pain
This report is part of a 12-month Clinical Context series.
By Nancy Walsh, Staff Writer, MedPage Today Published: August 26, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

The extent to which rheumatoid arthritis patients achieve their individual goals for physical activity can predict the beneficial effects of activity on pain and quality of life, a statistical modeling analysis showed.The belief that one can achieve one's goals -- a concept known as self-efficacy -- explained 31.4% of the indirect effects of physical activity on arthritis pain after six months, according to Keegan P. Knittle, MSc, from Leiden University in the Netherlands, and colleagues.Self-efficacy also explained 43.8% of change in physical quality of life and 60% of variance in mental quality of life at six months, both of which were significant differences, the Dutch researchers reported online in Arthritis Care & Research. Action Points Explain that the extent to which rheumatoid arthritis patients achieve their individual goals for physical activity can predict the beneficial effects of activity on pain and quality of life.Note that self-efficacy also explained some of the change in physical quality of life and most of the variance in mental quality of life at six months.

It has become clear that patients with rheumatoid arthritis can derive significant benefits from physical activity, but most patients do not meet the goal of exercising one half hour five days each week.

Self-efficacy and autonomous motivation have both been shown to be positively correlated with increased exercise in patients with rheumatoid arthritis, but a possible relationship with goal achievement and quality of life has not been determined.Accordingly, the researchers used multiple-mediation models "which assume that physical activity and goal achievement mediate the relationships between self-efficacy and autonomous motivation on the one hand, and either pain, physical quality of life, or mental quality of life on the other hand," they explained.

They enrolled 106 patients who completed questionnaires at baseline, providing detailed, numerical information about their attitudes and symptoms.Participants then completed a second questionnaire six months later in which they determined the extent to which they achieved their goals, and what the effects were on their arthritis symptoms and sense of well-being.
Three-quarters of the participants reported meeting their goals for physical activity by at least 50%, according to Knittle and associates.

For their analysis, the researchers then constructed a two-step model with autonomous motivation and self-efficacy as independent variables, goal achievement and physical activity as mediators, and age and sex as covariates.The model was designed to examine the indirect effects of each independent variable, adjusting not only for the contribution of the other independent variable but also for the covariates.

The mediation analyses first considered the associations between the independent variable and the mediators (a) and physical activity with pain (b).

The analysis found no direct association between physical activity and pain, but did show indirect effects (an × bn) of self-efficacy and goal achievement on pain and quality of life -- when mediated through goal achievement: Arthritis pain, a3 × b1 = −0.059 (95% CI −0.151 to −0.008) Physical quality of life, a3 × b1 = 0.670 (95% CI 0.128 to 1.593) Mental quality of life, a3 × b1 = 0.388 (95% CI 0.032 to 1.072) "The indirect effects through goal achievement may therefore reflect a tendency of highly self-efficacious individuals to set more difficult physical activity goals, perhaps involving more dynamic conditioning or strengthening exercises, which in turn have greater effects on arthritis pain," the researchers observed.

These results confirmed that patients with rheumatoid arthritis who are active consider themselves able to continue being active, with the implication that clinicians should attempt to foster self-efficacy in their patients, according to the researchers.Interventions that can increase self-efficacy for physical activity, they noted, include setting specific goals, developing action plans, and providing feedback."The idea behind these goal-setting interventions is that the more realistic and achievable a goal is, and the more concrete its plan of execution, the more likely it is to be achieved," wrote Knittle and colleagues.

Setting goals that are realistic is particularly important, they noted, because unmet goals can further diminish self-efficacy and autonomous motivation.Limitations included participant attrition and the unavailability of data on their specific activities.

Source reference:Knittle K, et al "Self-efficacy and physical activity goal achievement predict arthritis pain and quality of life among patients with rheumatoid arthritis" Arthritis Care Res 2011; DOI: 10.1002/acr.20587.
Primary source: Arthritis Care & Research

International Progress On Non-Communicable Disease Epidemic Jeopardized By UN Member States
26 August 2011
The fight against non-communicable diseases (NCDs) such as cancer, diabetes, cardiovascular disease, chronic respiratory disease and liver disease, is at grave risk, because of recent efforts by some countries to stall and...
[read article]

Complementary and Alternative Medicine

Complementary Medicine Used More by Health Care Workers
U.S. health care providers use complementary, alternative medicine more than support workers
FRIDAY, Aug. 26 (HealthDay News) -- U.S. health care workers, especially health care providers, are more likely to use complementary and alternative medicine (CAM) than the general, employed U.S. population, according to a study published online Aug. 22 in Health Services Research.

Pamela Jo Johnson, M.P.H., Ph.D., from the Allina Hospitals and Clinics in Minneapolis, and colleagues examined the personal use of 36 types of CAM therapies among U.S. health care workers. Data were collected from the 2007 Alternative Health Supplement of the National Health Interview Survey. A nationally representative sample of 14,329 employed adults, including a subsample of 1,280 adults employed in hospitals or ambulatory care settings, were examined. Health care workers were divided into four categories: providers, technicians, support workers, and other occupations. The odds of CAM use in each category in the past year were assessed by multivariate logistic regression.

The investigators found that, compared to the general population, health care workers were more likely to use CAM (76 versus 63 percent). Health care workers were significantly more likely to use and self-treat with CAM compared with employees in other industries. Health care workers in ambulatory care were significantly more likely to have used CAM in the past year compared to those working in hospitals. Health care providers were more likely to have past-year practitioner-based CAM use and self-treatment with CAM compared to support workers (adjusted odds ratio, 2.2 and 2.7, respectively).

"This study provides the first population-based description of CAM use by U.S. health care workers. Our analyses reveal that, overall, health care workers are significantly more likely to use CAM therapies, particularly mind-body therapies, than the employed U.S. population," the authors write.

AbstractFull Text (subscription or payment may be required)
Last Updated: August 26, 2011
Copyright © 2011 HealthDay. All rights reserved.

For Your Reading Pleasure

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

This Week Hosted By; Suture for a Living

Thank you for coming to Grand Rounds 7:48, the weekly collection of the some of the best in online medical writing from all (doctors, nurses, patients, healthcare professionals). Next week’s will be hosted by Health 3.0 Blog.Along with the excellent posts, I’ve included pictures of the changes cameras have gone through over the years – from the pin-hole camera to digital phone cameras. Enjoy!

A Few Submissions below, read all entries here

Dr. Schattner, MedicalLessons, talks about what she has learned from the offbeat and in some ways disturbing story of a young woman who's made a business of having had a rare form of cancer, epithe­lioid heman­gioen­dothelioma: Notes on Crazy Sexy Cancer

Carolyn is a heart attack survivor who blogs at HEART SISTERS. In her post, "How to be a good patient" , she shares her experiences and expertise she has gained in having a chronic illness.

Ryan, ACP Internist blog, looks at the recent trends in healthy lifestyle choices by adapting two recent studies (and adding a touch of humor): Smoking in front of the television must be really bad

Continue reading here

Friday, October 8, 2010

Hepatitis, Liver Cancer and Men

Hepatitis C, Liver Cancer and Men
Men develop liver cancer at twice the rate of women in the United States. In other countries, especially in Asia, the rate for men can be eight or 10 times that for women.
Why Liver Cancer Is More Prevalent In Males Than In Females
Production of a protein that promotes inflammation appears to be linked to the higher incidence of liver cancer in men than in women, researchers at the University of California, San Diego (UCSD) School of Medicine have determined in mouse studies. Their discovery that female mice produce far less of the protein called interleukin-6 (IL-6) in response to liver injury than males do, and that production of this protein is suppressed by estrogen, may point the way to therapies to reduce the incidence of liver cancer in males. IL-6 contributes to the chronic liver inflammation that leads to cancer.
The research team was led by Michael Karin, Ph.D., professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction. The findings will be published in the July 6 issue of the journal Science.
"Males show a higher rate of inflammation than females in the same diseases, including cancer," said Willscott Naugler, M.D., clinical instructor in UCSD's Department of Medicine and first author of the paper. "We wondered if increased inflammation was behind the higher incidence of liver cancer in males and, if so, how and why?"
Heptocellular carcinoma (HCC) -- a devastating complication of chronic liver disease and inflammation caused by risk factors such as hepatitis B and C viruses, or alcoholic liver disease -- makes up the majority of liver cancers in humans. Overall, men are three to five times more likely to develop HCC than women; however, in individuals who are under 50, HCC is seen seven to 10 times more frequently in men.
What are Symptoms of Liver Cancer in Men
Liver cancer symptoms are mostly asymptomatic during the early stages. The liver cancer symptoms in men begin to appear slowly as the disease progresses. If these signs and symptoms of liver cancer in men are overlooked, the disease can progress to an advanced stage that becomes very difficult to treat.
Let us now see what are symptoms of liver cancer in men
Erectile Problems : Men who suffer from cancers that affect their abdominal area may suffer from erectile dysfunction. This is because their genitals are very delicate and sensitive. Any disorder or change in biochemical level of the body may cause erectile problems. There are many changes occurring the man's body suffering from liver cancer. These changes cause erectile dysfunction in men with liver cancer. However, not every erectile dysfunction points to liver cancer. Get yourself examined to find out the underlying cause of this problem other than liver cancer.
Breast Enlargement
This may sound a bit weird, but one of the liver cancer symptoms in men is enlargement of breast. This means the breasts increase in size and are beyond the size of normal swelling. Many men often have their breast size increase to the size of a woman's breast. Their breasts become tender and are painful to touch. This is a very rare symptom that is not seen in many other disorders. Therefore, if a man experiences breast enlargement he should get himself examined for liver cancer.
Bloody Urine
One of the signs and symptoms of liver cancer in men is blood in urine. This is an indication of problems in liver, testicular cancer or prostate cancer as well. The liver gets filled with blood when the liver cells become cancerous. This causes the blood to flow out thrown the urinary system and thus observed in urine. If a man experiences this symptom, he needs to seek medical advice.Swollen TesticlesSwollen testicles are a common symptom of cancer in men. Sometimes the cancerous cells from liver may spread to the testicles leading to swellings or lumps in the testicles. Most of the time, these lumps are painless. This causes men to ignore this symptom and overlook the medical time bomb in their liver.
Men and Hepatitis C
,Men and women have different experiences in many aspects of their health, from life expectancy and the types of illnesses they will develop, to the number of visits they make to their GP.
Generalisations about men’s health include such things as: men take less care of their health; men take more risks in life; and men are less willing to visit health professionals.
Like all generalisations, they are not entirely true, and don’t consider many other factors affecting health, but doconta in some important truths about men’s health.
There are more men than women with hep C, and their health outcomes tend to be less favourable – there are many reasons for this,which include transmission, progression and treatment of hep C.
Hep C affects men and women differently
Men use injecting drugs more than women, and it is generally accepted that men are involved in more risky behaviours; these are some of the known reasons why men more so than women develop chronic hep C. What is less well understood is the way in which men are more susceptible than women to hep C infection. Some people are able to combat initial hep C infection and avoid progressing to chronic hep C; women are more likely to achieve this than men.
Liver fibrosis occurs faster and more frequently in men, and they also experience more long-term liver damage. Men who have cirrhosis are five times more likely to develop liver cancer than women who have cirrhosis.
Men typically consume more alcohol than women; this goes some way to explaining why men have more liver problems, but it is not the whole story.

Jacob George, Professorof Gastroenterology and Hepatic Medicine at the University of Sydney, says that hormona ldifferences between men and women may be part of the reason for liver fibrosis occurring faster in men, and for the greater incidence of liver cancer in men.
What are the barriers to men seeking treatment?
Evidence has shown that men are less likely than women to seek medical treatment in most circumstances. There are no simple explanations for this; but, as reported in the AustralianGovernment Department of Health and Ageing information paper Development of a National Men’s Health Policy 2008, men attend GPs less frequently, after being unwell for longer periods,and they have shorter, less in-depth consultations.These barriers to men being tested for hep C also affect their access to treatment.
Not being able to work while on treatment is a real fear for a lot of people. In cases where a man is the major income earner in a household, this is a very large consideration. Given that there is no certainty of clearing hep C, men may think twice when making decisions about treatment.
Treatment Side Effects From Standard HCV Therapy
“The potential loss of hair is something men just don’t like to face. Many men will also fear a loss of libido on treatment,” he says. “Doing treatment means explaining how you got hep C to those close to you, and especially your mates.”Professor George adds that men sometimes have a more chaotic lifestyle, and more psychiatric problems such as schizophrenia and depression; in some cases this may be a result of long-term drug use. These issues make it harder to access treatment, as well as making hep C treatment less of a priority.
Improving outcomes for men with hep C
Understanding that early detection can improvelong-term prognosis may encourage men to be tested; this is especially relevant where men think they may have been exposed to hep C but have no symptoms. Barriers to testing can also be broken down if men understand that treatment is readily available, and will be given without judgement. If they know exactly where to go for treatment and how to approach it, they are probably more likely to pursue a treatment program – and the fewer steps involved, the better.
Women respond to combination treatment for hep C better than men do, and have a higher clearance rate; this can make adherence more difficult for men.
Men who are suffering badly from side effects may be more likely to stop treatment when they consider they may have a smaller chance of clearing their hep C. Health professionals who understand men’s issues and provide appropriate support are vital to improving outcomes for men with hep C.
Some men may be more likely to consider treatment if they can see examples of others who have successfully completed treatment. Professor George points out that most men donot lose their jobs and are able to continue working throughout treatment. He believes that men would be more open to treatment if they could clearly see the benefits of clearing hep C. Some men may feel that hep C is something they just have to live with, or that the negatives of treatment out weigh the positives of clearance; exploring these issues further may help to highlight the importance of treatment.Putting the side effects of treatment into context with some of the long-term symptoms of chronic hep C may help; for example, men who are worried about experiencing sexual dysfunction while on treatment may not beaware that impotence is a common symptom in men with advanced cirrhosis.

There is a gap between providing treatment resources and making these resources easily accessible; targeting hep C treatment information to men would help close this gap. Men use health services less than women do, but this cannot be solely attributed to men’s attitudes towards their health. Development of a National Men’s Health Policy 2008 shows that men do respond to health messages aimed at them, and services that target men and present themselves as accessible are well utilised.
• Adrian Rigg is a freelance health writer who
writes for The Hep Review: