Showing posts with label bms-790052. Show all posts
Showing posts with label bms-790052. Show all posts

Friday, July 13, 2012

Geno 1-4: Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch

2012 pipeline report launched in Washington: HIV, HCV, TB, PEP, cure and vaccine research.

On July 21- 2012 HIV i-Base (U.K.) and Treatment Action Group (TAG) (U.S.) released their new comprehensive "2012 Pipeline Report"

The report is ready to view at the new website launched today by "TAG"

For the HCV community, there is a particular article in the report written by Tracy Swan and Karyn Kaplan you won't want to miss;

Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch.
The in depth report includes some of the following topics; HCV drug resistance, DAA drug-drug interactions, nucleosides and nucleotide polymerase inhibitors, HCV protease inhibitors, the next generation of drugs, HCV quad therapy, SVR-4 ,SVR-12, interferon free therapy, ABT-450/r, ACH-1625, BI 201335, bms-650032, bms-790052, Danoprevir, genotypes 1-4, GS-7977 Formally/PSI-7977, GS-9256, Lambda, MK-7009, TMC435 and much more....

The 2012 Pipeline Report: HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development by Polly Clayden, Simon Collins, Colleen Daniels, Nathan Geffen, Mark Harrington, Richard Jefferys, Coco Jervis, Karyn Kaplan, Erica Lessem, and Tracy Swan is available online at:
and as an interactive web report at:

Friday, September 30, 2011

AASLD-New Data On BMS-790052 and BMS-650032 to be presented by Bristol-Myers Squibb

September 30, 2011 11:19 AM EDT

Bristol-Myers Squibb to Present New Data Demonstrating Company’s Leadership in Liver Disease at The Liver Meeting® / AASLD Annual Meeting

  • Oral presentation on BARACLUDE® (entecavir) reinforces continued clinical development commitment in hepatitis B
  • Oral presentations on hepatitis C investigational compounds BMS-790052 and BMS-650032 demonstrate advancement of robust pipeline
  • Breadth of data highlights Company’s commitment to pursuing research that aims to improve the management of liver disease

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) announced today that 22 abstracts on the Company’s research in liver disease have been accepted for presentation at The Liver Meeting® 2011, the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco, November 4 - 8. Bristol-Myers Squibb is advancing a portfolio of compounds that has the potential to address unmet medical needs for patients with liver disease, including BARACLUDE® (entecavir) for chronic hepatitis B (CHB), and the investigational compounds BMS-790052, BMS-650032 and PEG-Interferon lambda (Lambda) for hepatitis C (HCV) and brivanib for hepatocellular carcinoma (HCC).

Key presentations include an oral presentation on BARACLUDE monotherapy vs. combination therapy for CHB and two oral presentations of Phase II data on the Company’s investigational HCV direct-acting antivirals (DAAs). These presentations will highlight:

  • The first data from the BE-LOW study, a Phase IIIb comparative study of BARACLUDE plus tenofovir vs. BARACLUDE monotherapy in treatment-naïve adults with CHB
  • The first results from a Phase IIb study of the NS5A replication complex inhibitor BMS-790052 plus peginterferon alfa and ribavirin (alfa/RBV) in treatment-naive HCV genotype 1 and 4 patients, evaluating virologic response through 12 weeks on treatment (eRVR)
  • The first results of a Phase IIa study of the dual DAA regimen of BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected patients who have not responded to prior alfa/RBV therapy (null responders), evaluating sustained virologic response 12 weeks post-treatment (SVR12)

“Bristol-Myers Squibb is at the forefront of innovation in researching the treatment of liver diseases. In hepatitis C, where there remain considerable unmet medical needs, our goal is to increase treatment options for patients by developing a portfolio of compounds with different mechanisms of action,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data we are presenting at the Liver Meeting help to expand our understanding of the potential efficacy and safety profiles of these investigational compounds and support the recent initiation of a broad Phase III development program in HCV.”

The Company will also present new data that further describe the mechanistic and clinical profile of Lambda, and real-world data that add to the understanding of the prevalence of and current treatment patterns in HBV, HCV and HCC, including an oral presentation of data from the BRIDGE study in HCC. The BRIDGE study is designed to develop global understanding of HCC, including assessment of treatment by geography and etiology, and associated clinical outcomes.

The complete list of Bristol-Myers Squibb data presentations is below. Abstracts can be accessed on the AASLD website at

Abstract Number Title Date/Time
Hepatitis B: BARACLUDE Clinical Data


Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir (TDF) in nucleos(t)ide-naïve patients with chronic hepatitis B (CHB): the BE-LOW study Presidential Plenary III

Nov. 8

8:00 am PST

Hepatitis B: Outcomes Research / Real-World Data


Real World Data on Long Term Treatment Initiation in patients with Chronic Hepatitis B: cohort observations in France, Germany, Poland, Romania and Turkey Nov. 5


Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis Nov. 5


Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Entecavir versus Tenofovir Nov. 5


Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Oral Antivirals Recommended by Current Guidelines versus Oral Antivirals Not Recommended by Current Guidelines Nov. 5
Hepatitis C: Direct-Acting Antiviral Data


Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response (SVR12) in HCV Genotype 1b-Infected Null Responders Nov. 7

3:30 pm PST



BMS-790052, A NS5A Replication Complex Inhibitor, Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naive HCV-Genotype 1 or 4 Patients: Phase 2b AI444010 Study Interim Week 12 Results Presidential Plenary III

Nov. 8

9:00 am PST

Poster #381 Evaluation of drug interaction potential of the HCV protease inhibitor BMS-650032 at 200mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers Nov. 5
Poster #LB-20 Combination Therapy of Treatment-Naïve and Nonresponder Patients with HCV Genotype 1 Infection with BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alfa-2a and Ribavirin Nov. 7
Poster #LB-22 BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alpha-2b and Ribavirin in Japanese Treatment-Naïve and Nonresponder Patients with Chronic HCV Genotype 1 Infection Nov. 7
Poster #1362 Single-Dose Pharmacokinetics of BMS-790052 in Subjects with Hepatic Impairment Compared With Healthy Subjects Nov. 7
Poster #1340 BMS-790052 Has No Effect on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Healthy Female Subjects Nov. 7
Hepatitis C: PEG-Interferon Lambda Data
Poster #376 The Effect of Pegylated Interferon Lambda on the Expression of Interferon Stimulated Genes in Whole Blood in Chronic Hepatitis C Patients in a Phase 2a Study Nov. 5
Poster #1058 Implementation of an HCV Model for Il-28B Genotype Treatment Duration Optimization and Cure Rate Maximization for Pegylated Interferon Lambda Nov. 6
Poster #1343 Pegylated Interferon Lambda Ameliorates Ribavirin (RBV)-Induced Anemia in HCV Patients by Maintaining Compensatory Erythropoiesis: Analysis of EMERGE Phase 2b Results through Week 12 Nov. 7
Poster #1344 Safety and Efficacy of Pegylated Interferon Lambda (peg-lambda) Compared to Pegylated Interferon α-2a (peg-alfa) in HCV-Infected Patients (G1/2/3) With Compensated Cirrhosis: EMERGE Phase IIB Efficacy and Safety Results through Week 12 Nov. 7
Poster #1363 Less severe flu-like symptoms with PEG-Interferon Lambda in Phase IIb Study of treatment-naive chronic hepatitis C (CHC) patients Nov. 7
Hepatitis C: Epidemiology / Real-World Data
Poster #412 Prevalence of HCV and Host IL28B Genotypes in China Nov. 5
Poster #1045 Adverse Events in Patients With Chronic Hepatitis C Treated With PegIFN-alfa and Ribavirin in Real-World Setting Nov. 6
Poster #1084 Virologic Response among Hepatitis C (HCV) Patients Treated in Clinical Practice Nov. 6
Poster #1736 Single nucleotide polymorphisms near IL28B and IL28A genes are associated with spontaneous seroclearance of HCV RNA in untreated patients with HCV infection Nov. 7
Hepatocellular Carcinoma: Outcomes Research


Observations of Hepatocellular Carcinoma (HCC) Management Patterns from the Multinational HCC BRIDGE Study: First Overall Analysis of the North American Cohort Nov. 811:15 am PST



BARACLUDE is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The following points should be considered when initiating BARACLUDE:

  • This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naïve and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated liver disease.
  • Virologic, biochemical, serologic, and safety data are available from a controlled study in adult subjects with chronic HBV infection and decompensated liver disease.
  • Virologic, biochemical, serologic, and safety data are available for a limited number of adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy.



  • Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
  • Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic HBV infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART).
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals.

Warnings and Precautions

  • Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.
  • Lactic acidosis with BARACLUDE use has been reported, often in association with hepatic decompensation, other serious medical conditions, or drug exposures. Patients with decompensated liver disease may be at higher risk for lactic acidosis. BARACLUDE should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Adverse Reactions

  • In clinical trials in patients with compensated liver disease, the most common (≥3%) adverse reactions of any severity with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia.
  • In the decompensated liver disease trial, the most common adverse reactions of any severity among patients treated with BARACLUDE, regardless of causality, included: peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%). In this trial, 18% (18/102) of BARACLUDE patients and 20% (18/89) of adefovir patients died during the first 48 weeks of therapy. The majority of those deaths were due to liver related causes.

Drug Interactions

BARACLUDE is primarily eliminated by the kidneys, therefore coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug. Patients should be monitored closely when receiving BARACLUDE with other renally-eliminated drugs.

Pregnancy and Nursing Mothers

  • There are no adequate and well-controlled studies of BARACLUDE in pregnant women. BARACLUDE should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.
  • There are no studies on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.
  • It is not known whether BARACLUDE is excreted into human milk; however, many drugs are excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants from BARACLUDE, risks and benefits should be considered when deciding whether to discontinue breast-feeding or discontinue BARACLUDE in nursing women.

Pediatric Use

  • Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.

Renal Impairment

  • Dosage adjustment of BARACLUDE is recommended for patients with a creatinine clearance <50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.
  • The safety and efficacy of BARACLUDE in liver transplant recipients are unknown. Renal function must be carefully monitored both before and during treatment with BARACLUDE in a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus.

Dosage and Administration

BARACLUDE should be administered on an empty stomach (at least 2 hours after a meal and at least 2 hours before the next meal).

The recommended dose of BARACLUDE:

  • in nucleoside-naïve adults and adolescents (16+ yrs) with compensated liver disease is 0.5 mg once daily
  • in adults and adolescents (16+ yrs) with compensated liver disease, and refractory to lamivudine or with known lamivudine or telbivudine resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) is 1 mg once daily
  • in adults with decompensated liver disease is 1 mg once daily

The optimal duration of treatment with BARACLUDE for patients with chronic HBV infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

Additional Information

Patients should be advised that treatment with BARACLUDE has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

Please see Full Prescribing Information, including boxed WARNINGS, available at

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit or follow us on Twitter at

Bristol-Myers Squibb CompanyMedia:Cristi Barnett, 609-252-6028cristi.barnett@bms.comorInvestors:John Elicker,

Source: Bristol-Myers Squibb Company

Tuesday, September 20, 2011

Hepatitis C In The News; BMS-790052

From Natap
ICAAC: High Rates of SVR24 for BMS-790052, an NS5A Replication Complex Inhibitor, in Combination With PegIFN-alfa-2a and Ribavirin: Phase 2a Trial in Treatment-Naive HCV Genotype 1 Subjects

ICAAC: BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients -

Could engineered fatty particles help prevent AIDS?
Liposomes block HIV infection in early tests; could be a cost-effective preventive for developing countries

HIV vaccines are in their infancy, and effective microbicides to prevent sexual transmission of HIV still don't exist. Protection is especially needed for women, who make up nearly half of all global cases. Researchers at Children's Hospital Boston envision a new way for women to protect themselves before sex: an applicator filled with specially formulated fatty particles called liposomes.

In tests led by Daniel Kohane, MD, PhD, director of the Laboratory for Biomaterials and Drug Delivery at Children's Hospital Boston, liposomes inhibited HIV infection in cell culture and appeared safe in female mice when injected intravaginally. The findings are reported in the November issue of the journal Biomaterials, published online September 19.

Liposomes are spherical particles with a double outer layer of lipids (fats) and hollow centers. They are relatively easy and cheap to engineer, and thus present a viable option for developing countries, where the cost of anti-HIV drugs bars access for most people.

Liposomes can be filled with drugs or other compounds, but in this case, Kohane and colleagues found, to their surprise, that the liposomes alone were effective in blocking infection.

"We had been planning do much more complex things, like putting ligands on the surface to increase binding to HIV," says Kohane. "It was a surprise that liposomes alone worked so well. Simplicity is always better – if liposomes work by themselves, we may not need anything else, and it would be cheaper and potentially much safer."

Kohane and colleagues hope to conduct further tests to better understand how the liposomes are blocking infection. They bind to HIV, perhaps interfering with the virus's ability to fuse with cell membranes, the first step in infection.

"The idea, simplistically, is that liposomes look like cell membranes," says Kohane, "so maybe we could use them as decoys to prevent HIV infection."

Kohane and colleagues formulated a range of liposomes using various naturally occurring and synthetic lipids and screened them systematically in cell cultures. Several formulations showed a good therapeutic profile, protecting the cells from HIV infection without being toxic. Especially effective were liposomes containing cardiolipin, a fat that was first found in animal hearts; performance was further improved by adding a synthetic phospholipid.

Tested in female mice, these formulations caused little or no inflammation, which can compromise the vaginal lining and increase the risk of HIV transmission. Imaging confirmed that the liposomes remained in place or left the body, but did not travel beyond the vagina.

"This research makes an important contribution towards creating a safe and effective form of HIV prevention for women," says Nikita Malavia, PhD, the study's first author, who worked in Kohane's lab and in the lab of Robert Langer, ScD, of MIT. "Women in areas such as sub-Saharan Africa often cannot control their male partners' use of condoms, making them three times more likely to be HIV-positive than men. This technology could enable women to take control in their own hands."

Though some intravaginal compounds are in the pipeline, none are available yet. The advantage of using liposomes is that they are inexpensive, easy to formulate into ointments or gels, and stable for long periods of time, making them a particularly good option in resource-poor settings.
Kohane hopes to get further funding to test liposome formulations in other animal models.
The study was funded by the Grand Challenges in Global Health initiative and the National Institutes of Health.

About Children's Hospital Boston
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Children's, visit:

Scientist Suggests That Squalamine Be Explored As A Human Antiviral Agent
20 September 2011
A compound initially isolated from sharks shows potential as a unique broad-spectrum human antiviral agent, according to a study led by a Georgetown University Medical Center investigator and reported in the Proceedings of...

Woman exposed to Hepatitis C gives emotional testimony
Las Vegas, NV (KTNV) -- The Hepatitis C civil trial continued Monday with emotional testimony from Anne Arnold, who contracted the disease during an outbreak that became public in 2008.
"I pride myself on being a strong woman and this took me right down," says Arnold.
Her nightmare began in July, 2007 at the Southern Nevada Endoscopy Center. It was Friday the 13th and Anne went in for a routine colonoscopy.
That was the day she contracted Hepatitis C... Read More
Watch Video

Obama’s deficit plan targets drug companies, hospitals and future Medicare beneficiaries
By Associated Press,WASHINGTON — Health care savings in President Barack Obama’s deficit-reduction plan would squeeze future Medicare recipients, cut payments to drug companies and hospitals, and shift costs to states.

Still, some advocates say the president’s approach is less painful than other major ideas being debated this year, from privatizing Medicare to letting the states run Medicaid without a federal guarantee that the poor would get needed care.

“This is a question of ‘compared to what?’” said John Rother, president of the National Coalition on Health Care, a research and advocacy group. “I would describe this as an attempt to spread the pain pretty broadly. While it does hit Medicare beneficiaries, it’s better than most of the alternatives we’ve seen thus far, which would involve bigger hits.”

Obama did promise Medicare beneficiaries that he’d veto any legislation asking them to sacrifice without also raising taxes on upper-income earners. But he didn’t issue them a complete pass.

Instead, his administration is borrowing from corporate America’s playbook by proposing to raise a range of costs for future retirees, while mostly shielding Medicare’s 48 million current beneficiaries. Under the president’s plan, starting in 2017:

—Upper-income beneficiaries would pay higher monthly premiums for outpatient and prescription coverage. Eventually about a quarter of all Medicare beneficiaries would be hit with the higher income-related premiums that only a small share of seniors now pay.

—Newly signed-up beneficiaries would pay a penalty if they also purchase private insurance that covers all or most of Medicare’s copayments and deductibles. Administration officials say such insurance encourages over-treatment.

—New beneficiaries would pay a $100 copayment for home health services, unless they have just been discharged from a hospital or nursing home.

—New beneficiaries would pay a higher annual deductible for outpatient services. The so-called Part B deductible, currently $162, is indexed for inflation. It would go up by $25 for new enrollees in 2017, 2019 and 2021.

“You can’t reduce the deficit without making some people pay more or get less,” said Paul Van de Water, a senior analyst with the Center on Budget and Policy Priorities, which advocates for the poor. “If you think there should be no cuts in Medicare, anywhere, then this obviously goes too far. If, at the end of the day, you recognize that they have to make some further reductions, then these are about the best you can do.”

Try telling that to the pharmaceutical industry. Obama’s plan would cut their payments by $135 billion over 10 years, accounting for more than one-third of his total health care savings. The president wants drug makers to pay rebates to Medicare, along the lines of what they now pay Medicaid. The Pharmaceutical Research and Manufacturers of America says it would lead to the loss of thousands of jobs in the industry.

Hospitals and nursing homes, slated for a mix of cuts and efficiency measures, are also complaining. The American Hospital Association says if Obama’s plan becomes law, hospitals and related businesses would lose 200,000 jobs by 2021.

Doctors also have reason to be concerned. Without endorsing any particular fix, Obama’s plan assumes that Congress will address the main issue facing doctors: a scheduled 30 percent cut in Medicare payments next year due to a previous budget law gone awry. A solution being considered by congressional advisers would cut payments to specialists and freeze rates for primary care doctors.

Obama also wants to give additional authority to a new agency called the Independent Payment Advisory Board, which could force further cuts for medical providers.

All told, Obama’s plan would cut Medicare by $248 billion over 10 years and squeeze another $72 billion from Medicaid. Some of Medicaid savings involve shifting costs to the states by rejiggering the federal payment formula and limiting a strategy currently used by states to draw more federal dollars.

Two leading organizations that supported Obama’s health care overhaul law are expressing concerns about his latest plan. AARP says it could result in arbitrary cuts to Medicare. Families USA, a liberal advocacy group, says the Medicaid cuts could undermine coverage for the uninsured.
Copyright 2011 The Associated Press. All rights reserved.
This material may not be published, broadcast, rewritten or redistributed.

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Sunday, September 18, 2011

BMS-790052-Positive results from a Phase II trial "83% SVR in 24wks"

RTTNews) - Bristol-Myers Squibb Co. (BMY: News ) Saturday revealed positive results from a Phase II trial of its experimental drug BMS-790052 in hepatitis C patients.

The phase II study analyzed 48 treatment-naïve genotype 1 hepatitis C patients who received one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with standard care peginterferon alfa-2a and ribavirin for 48 weeks.

The study's primary endpoint was the proportion of patients with extended rapid virologic response, defined as undetectable viral load at both Weeks 4 and 12.

The study showed that BMS-790052 in combination with peginterferon alfa and ribavirin maintained undetectable viral load at 24 weeks post-treatment in 83 percent of patients at a dose of 60 mg and 10 mg, and 42 percent at a dose of 3 mg. This compares with 25 percent of patients in peginterferon alfa and ribavirin control group after 48 weeks of combination therapy.

In this study, serious events were reported in one patient from each of the BMS-790052 treatment groups and in zero patients from the control group.

Adverse events occurring in at least four patients in any cohort were consistent across BMS-790052 treatment arms and the placebo arm, and included anemia, nausea, neutropenia, and rash. The addition of BMS-790052 to peginterferon alfa and ribavirin therapy did not result in any apparent incremental hematologic, hepatic or dermatologic adverse events.

The data were reported today at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago.

Bristol-Myers said the investigational direct acting antiviral BMS-790052 is now in Phase III development.

"The hepatitis C treatment landscape is rapidly evolving and although there have been positive advances recently, there remains a need for additional therapies with a more favorable efficacy and safety profile," said Stanislas Pol, head of the Hepatology unit at Cochin Hospital, Paris, France.

"In this Phase II study, adding BMS-790052 once daily to peginterferon alfa and ribavirin produced SVR rates and safety findings that warranted further development of BMS-790052."

Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development.

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
Press Release
September 17, 2011 05:00 PM Eastern Daylight Time

BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients

In this study, adverse event profile of regimen containing BMS-790052 was consistent with that of treatment with peginterferon alfa and ribavirin plus placebo
Company has initiated Phase III development program for BMS-790052
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a Phase II clinical trial of 48 treatment-naive genotype 1 hepatitis C infected patients in which treatment with BMS-790052, an NS5A replication complex inhibitor, in combination with peginterferon alfa and ribavirin (pegIFNalfa/RBV) maintained undetectable viral load at 24 weeks post-treatment (SVR24) in 83% (60 mg), 83% (10 mg) and 42% (3 mg) of patients, compared with 25% of patients in the pegIFNalfa/RBV control group after 48 weeks of combination therapy. In this study, serious adverse events were reported in one patient (8.3%) from each of the BMS-790052 treatment groups and in zero patients from the control group. The data were reported today at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago. The investigational direct acting antiviral BMS-790052 is now in Phase III development.

“The hepatitis C treatment landscape is rapidly evolving and although there have been positive advances recently, there remains a need for additional therapies with a more favorable efficacy and safety profile,” said Stanislas Pol, MD, PhD, Professor of Hepatology at Université Paris V (René Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. “In this Phase II study, adding BMS-790052 once daily to peginterferon alfa and ribavirin produced SVR rates and safety findings that warranted further development of BMS-790052.”

Study Results

BMS-790052 plus pegIFNalfa/RBV achieved higher rates of SVR24 compared to pegIFNalfa/RBV alone across all BMS-790052 treatment groups [BMS-790052: 60 mg: 83% (n=10/12), 10 mg: 83% (10/12), 3 mg: 42% (5/12); control: 25% (3/12)].

Adverse events (AEs) leading to discontinuation with BMS-790052 plus pegINFalfa/RBV were comparable with treatment with pegIFNalfa/RBV plus placebo. One patient (8.3%) in each of the 3 mg and 10 mg groups and four patients (33.3%) in the 60 mg group discontinued due to AEs, compared with two patients (16.7%) in the control group. Reasons for discontinuation were a diverse set of AEs sometimes associated with the use of pegIFNalfa/RBV.

Serious adverse events (SAEs) and overall AEs were comparable across study arms. The addition of BMS-790052 to pegIFNalfa/RBV therapy did not result in any apparent incremental hematologic, hepatic or dermatologic adverse events. One patient (8.3%) in each of the BMS-790052 treatment groups experienced a SAE during therapy compared with zero patients in the control group. On-treatment Grade 3-4 AEs were: BMS-790052 60 mg: 33.0%, 10 mg: 25.0%, 3 mg: 8.3%; control: 41.7%. One patient (8.3%) in each of the BMS-790052 3 mg and 60 mg groups experienced hemoglobin <10 g/dL, compared with zero patients in the 10 mg and control groups. AEs occurring in at least four patients (33.3%) in any cohort were consistent across BMS-790052 treatment arms and the placebo arm, and included the following events of interest: anemia (BMS-790052: 60 mg: 50.0%,10 mg: 41.7%, 3 mg: 25.0%; control: 41.7%), nausea (BMS-790052: 60 mg: 33.3%,10 mg: 33.3%, 3 mg: 41.7%; control: 50.0%), vomiting (BMS-790052 60 mg: 33.3%, 10 mg: 8.3%, 3 mg: 16.7%; control: 0%), neutropenia (BMS-790052: 60 mg: 16.7%,10 mg: 33.3%, 3 mg: 25.0%; control: 41.7%), and rash (BMS-790052: 60 mg: 16.7%,10 mg: 33.3%, 3 mg: 33.3%; control: 25.0%).

Erythropoietin use was comparable across all study arms. Three patients (25.0%) in each of the BMS-790052 10 mg and 60 mg groups and one patient (8.3%) in the 3 mg group required erythropoietin, compared with two patients (16.7%) in the control group. The use of filgrastim (G-CSF) in the study groups was: BMS-790052 60 mg: 0%, 10 mg: 25.0%, 3 mg: 16.7%; control: 16.7%.

About the Study

This double-blind study randomized 48 treatment-naïve HCV genotype 1-infected, non-cirrhotic patients 1:1:1:1 (n=12/arm) to receive one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with peginterferon alfa-2a and ribavirin for 48 weeks. The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR), defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. Primary endpoint data were previously reported at EASL 2010 in Vienna, Austria.

About BMS-790052

Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. BMS-790052 is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to one quarter may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit or follow us on Twitter at

Bristol-Myers Squibb Forward Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Bristol-Myers Squibb
Sonia Choi, 609-252-5132
Cristi Barnett, 609-252-6028

John Elicker, 609-252-4611

Tuesday, September 6, 2011

Dramatic Changes in Hepatitis C Treatment Expected to Continue

Dramatic Changes in Hepatitis C Treatment Expected to Continue
From Anadys Pharmaceuticals President and CEO Steve Worland
Steve Worland 9/6/11

Earlier this year the FDA approved telaprevir (Incivek) from Vertex Pharmaceuticals and boceprevir (Victrelis) from Merck for the treatment of hepatitis C. Both agents are protease inhibitors and represent the first approvals of direct acting antivirals for hepatitis C. Direct acting antivirals are a broad class of agents that act to block the growth of viruses by directly disrupting essential viral functions. The benefit of these drugs for hepatitis C follows the dramatic success of this class over the last 15 years in HIV. Now the future advances of direct acting antiviral therapy for hepatitis C is expected to follow a central theme of their use in HIV: that combination of multiple antivirals in a single treatment regimen will provide greater benefit than use of any one antiviral drug alone.

The new protease inhibitors were approved for use only in combination with two previously approved agents, pegylated interferon and ribavirin. The addition of either protease inhibitor increased clinical cure rates, known formally as sustained viral response (SVR) rates, by 30 to 40 percentage points over control groups receiving the standard pegylated interferon and ribavirin alone. As dramatic as these improvements are, there is a good chance for even more dramatic improvements if all-oral regimens, assembled by combining multiple direct acting antivirals, are able to maintain high cure rates while eliminating injectable interferon and its associated flu-like side effects that patients have long sought to avoid.

Next in the development queue are three agents that entered Phase III development this year, including two additional protease inhibitors (TMC435 from Johnson & Johnson’s Tibotec unit and BI201335 from Boehringer Ingelheim) and a cyclophilin inhibitor that disrupts a host function required for viral replication (alisporivir from Novartis). All three Phase III programs are exploring a modality similar to the approved agents, i.e. addition of a single new agent to the standard pegylated interferon/ribavirin. The ongoing Phase III programs will hope to demonstrate one or more advantage over the recently approved agents, potentially including better tolerability, further increases in cure rates, shorter duration of therapy and/or an increased proportion of patients successfully treated with shortened therapy. While such improvements may well be achieved, they may become less important or even irrelevant if the rapidly expanding number of direct acting antiviral combination trials leads to identification of new regimens that surpass all regimens that are based on a single antiviral drug added to the old standard regimen.

Investigation of direct acting antiviral combination regimens has exploded in the last 12 months. This advance has become possible because of the diversity of antiviral mechanisms distinct from protease inhibitors that are now represented in the pipeline of hepatitis C drugs in Phase II development across the industry. Diverse mechanisms are important because they typically provide distinct resistance profiles, and antiviral combinations are being assembled using new compounds with non-overlapping resistance profiles to provide a greater barrier to the development of antiviral resistance. Additional factors that are considered important in assembling optimal combinations include the safety and tolerability profile of each agent, compatible pharmacokinetic profiles and a low potential for unfavorable drug-drug interactions. The more extensively characterized each individual antiviral drug is, the lower the risk of an unanticipated negative interaction between the drugs once combined.

New mechanisms other than protease inhibitors that have entered large Phase IIb studies include non-nucleoside polymerase inhibitors (setrobuvir from my company, Anadys Pharmaceuticals, as well as tegobuvir from Gilead Sciences and filibuvir from Pfizer). Another class is composed of nucleoside/tide polymerase inhibitors (mericitabine from Roche and PSI-7997 from Pharmasset). There’s also an NS5a inhibitor in Phase IIb development (BMS-790052 from Bristol-Myers Squibb).

At Anadys, we chose to focus on the non-nucleoside class of polymerase inhibitors for several reasons. We recognized an inherent potential for an excellent safety profile, given the absence of structurally related host targets and the ability to generate inhibitors without relying on close analogs of host metabolites. The excellent safety record to date for setrobuvir is consistent with our initial expectations regarding safety. The diversity of applicable chemotypes also led us to expect a clear path to patent-protected intellectual property, exemplified by our recently issued U.S. patent covering setrobuvir. In other antiviral drug classes, especially nucleosides/tides and NS5a inhibitors, the range of useful chemical space discovered to date is considerably more narrow, leading to the potential for more interference on the IP side. Lastly, we recognized that a potential liability of the non-nucleoside class, a lower genetic barrier to resistance, could likely be addressed if we were able to engineer a high pharmacological barrier to resistance into candidate molecules. This recognition was based on the lessons learned about non-nucleosides in the 1990s in HIV. Specifically, there were two disappointing product introductions of non-nucleoside products for HIV that were plagued with rapid emergence of resistance—nevirapine (Viramune) from Boehinger Ingelheim and delavirdine (Rescriptor), now marketed by Pfizer. After that came efavirenz (Sustiva) from Bristol-Myers Squibb, so named for its ability to last longer in the bloodstream, which demonstrated that a non-nucleoside with good potency and a prolonged plasma half-life could demonstrate a dramatically improved resistance profile. While we reasoned that a similar solution would be applicable in hepatitis C, we also understood the significant medicinal chemistry challenge to accomplish this objective and furthermore understood that the technology platform at Anadys was exquisitely well matched to the molecular engineering challenge of simultaneously optimizing potency and pharmacokinetics. The excellent resistance profile of setrobuvir observed to date demonstrates the high pharmacological resistance barrier achieved with setrobuvir, and data to date is consistent with our idea that a high pharmacological barrier to resistance could serve in place of a high genetic barrier to resistance.

As the hepatitis C development landscape continues to advance, we expect to see an increasing number of direct acting antiviral combination trials and subsequent approval of new agents based on data derived from such trials. The FDA as well as patient advocacy groups have been strong proponents of investigating antiviral drug combinations prior to approval of individual components, and I expect an ongoing favorable regulatory environment towards combination trials provided that each individual agent is sufficiently well-characterized.

Companies that believe in the importance of antiviral combinations for future commercial relevance in hepatitis C are likely to have opinions as to how many drugs they believe will be needed in antiviral combination regimens, and are likely to pursue strategies directed at accessing at least that number of compounds if not a greater number as insurance against attrition. Mathematical modeling from Perelson and colleagues suggests that interferon-free regimens will need to contain three or four distinct antiviral mechanisms to result in viral eradication (SVR) prior to emergence of resistance. To access the required number of drugs, companies have several business alternatives available. They can rely on maturation of their internal pipelines, although few if any companies appear today to have sufficiently robust internal pipelines to rely exclusively on this approach. Companies can rely on cross-company clinical collaboration agreements to gain initial data on particular antiviral combinations, although this approach doesn’t directly answer the question of how to seek approval and launch effective marketing efforts for the individual components studied in a cross-company antiviral drug combination trial. Companies with antiviral drugs other than protease inhibitors can look to utilize one of the approved protease inhibitors as one other mechanism, analogous to the use of interferon and ribavirin in the development of the protease inhibitors to date, but this will only be a partial solution if three or more DAAs are required. Lastly, companies can gain exclusive access to antiviral drugs outside their current pipelines through a variety of business deals, allowing them to quickly assemble a pipeline with sufficient depth to increase the chances of being early to market with a successful combination regimen. To date, examples of all these strategies except combination with one of the approved protease inhibitors have been pursued by one or more companies. Going forward, these efforts across the industry are likely to culminate in approval of direct acting antiviral combination regimens, with the ultimate goal of assembling combinations powerful enough to eliminate interferon and perhaps ribavirin from hepatitis C therapy. These advancements may occur within the next few years, and if realized, would represent yet another dramatic improvement in hepatitis C therapy, at least as dramatic as the advances recently realized with the approval of the first protease inhibitors.

Read More;

Related Posts @ Xconomy
Combination Drugs Are The Future for Hepatitis C
Using HIV as Model, Anadys Develops Drug Cocktail Ingredient for Hepatitis C
Hepatitis C Drug From Anadys Shows Quick Virus-Killing Punch
Anadys Keeps Surging, as Hepatitis C Drug Data Trickles In
Anadys Drug Found Safe in Small Study, Aims to Contend in New Class of Hepatitis C Meds

Wednesday, August 17, 2011

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hepatitis B

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

Healthy You

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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


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

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

For Your Reading Pleasure

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

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

A Few Submissions, read all entries here

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

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

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

Read all entries here

Off The Cuff

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SOURCE: Diabetes Care

New On The Blog;
Murdoch researchers attempt to thwart hep C virus
Use of New HCV Protease Inhibitors ‘Not That Simple’
Incivek/Victrelis; New approvals may change treatment for hepatitis C
Cancer; Controversies in Phase I Clinical Trials

Tuesday, August 16, 2011

Hepatitis Digest;HCV abstract-BMS-790052, Liver Cancer,Vitamin D and Diabetes

HCV abstracts

Aug 2011;
Multiple ascending dose study of BMS-790052, an NS5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1

Nettles RE, Gao M, Bifano M, Chung E, Persson A, Marbury TC, Goldwater R, Demicco MP, Rodriguez-Torres M, Vutikullird A, Fuentes E, Lawitz E, Carlos Lopez-Talavera J, Grasela DM; Hepatology (Aug 2011)

The antiviral activity, resistance profile, pharmacokinetics (PK), safety and tolerability of BMS-790052, an NS5A replication complex inhibitor, were evaluated in a double-blind, placebo-controlled, sequential panel, multiple ascending dose study. Thirty patients with chronic hepatitis C virus (HCV) genotype 1 infection were randomized to receive a 14-day course of BMS-790052 (1, 10, 30, 60 or 100 mg once daily or 30 mg twice daily) or placebo in a ratio of 4:1.

RESULTS: The mean maximum decline from baseline in HCV RNA ranged from 2.8 to 4.1 log(10) IU/mL; the placebo group showed no evidence of antiviral activity. Most patients experienced viral rebound on or before day 7 of treatment with BMS-790052 monotherapy; viral rebound was associated with viral variants that had been previously implicated in resistance development in the in vitro replicon system. The PK profile was supportive of once-daily dosing with median peak plasma concentrations at 1-2 hours postdose and mean terminal half-life of 12-15 hours. Steady state was achieved following 3-4 days of daily dosing. BMS-790052 was well tolerated in all dose groups with adverse events occurring with a similar frequency in BMS-790052- and placebo-treated groups. There were no clinically relevant changes in vital signs, laboratory, or electrocardiogram parameters.

CONCLUSION: BMS-7590052 is the first NS5A replication complex inhibitor with multiple dose proof-of-concept in clinic. At doses of 1-100 mg daily, BMS-790052 was well-tolerated, had a PK profile supportive of once-daily dosing, and produced a rapid and substantial decrease in HCV-RNA levels in patients chronically infected with HCV genotype 1. (HEPATOLOGY 2011.)

Genotypic and phenotypic analysis of variants resistant to HCV NS5A replication complex inhibitor BMS-790052: In Vitro and In Vivo correlations
Fridell RA, Wang C, Sun JH, O' Boyle DR, Nower P, Valera L, Qiu D, Roberts S, Huang X, Kienzle B, Bifano M, Nettles RE, Gao M; Hepatology (Aug 2011)

The NS5A replication complex inhibitor BMS-790052 inhibits hepatitis C virus (HCV) replication with picomolar potency in preclinical assays. This potency translated in vivo to a substantial antiviral effect in a single-ascending dose study and a 14-day multiple-ascending dose (MAD) monotherapy study. However, HCV RNA remained detectable in genotype 1a-infected patients at the end of the MAD study. In contrast, viral breakthrough was observed less often in patients infected with genotype 1b and, in several patients, HCV RNA declined and remained below the level of quantitation (<25 IU/mL) through the duration of treatment. Here we report results of the genotypic and phenotypic analyses of resistant variants in 24 genotype 1-infected patients who received BMS-790052 (1, 10, 30, 60 and 100 mg, once daily or 30 mg, twice daily) in the 14-day MAD study. Sequence analysis was performed on viral cDNA isolated from serum specimens collected at baseline and days 1 (4, 8, and 12 hours), 2, 4, 7, and 14 postdosing. Analyses of the sequence variants (i) established a correlation between resistant variants emerging in vivo with BMS-790052 treatment and those observed in the in vitro replicon system (major substitutions at residues 28, 30, 31 and 93 for genotype 1a, and residues 31 and 93 for genotype 1b); (ii) determined the prevalence of variants at baseline and the emergence of resistance at different times during dosing; and (iii) revealed the resistance profile and replicative ability (fitness) of the variants.

CONCLUSION: Although resistance emerged during monotherapy with BMS-790052, the substantial anti-HCV effect of this compound makes it an excellent candidate for effective combination therapy. (HEPATOLOGY 2011.)

BMS-790052 Plus BMS-650032

From CCO;EASL 2011
Expert Analysis
BMS-790052 Plus BMS-650032 With or Without Peginterferon alfa-2a/Ribavirin in Previous Null Responders With Genotype 1 HCV Infection
AJ is a genotype 1 HCV–infected patient who experienced a null response with previous peginterferon/ribavirin therapy. He is hesitant to start treatment with telaprevir or boceprevir once approved, as he does not feel that that the chances of SVR are worth the adverse effects he experienced with peginterferon previously. He is curious to know whether any data thus far have shown SVR among patients treated with an interferon-free regimen.

How can you advise this patient?

To View Capsule Summary Free Registration Is Required

Stefan Zeuzem, MD: In another study investigating the efficacy of combining DAA agents, Lok and colleagues[35] combined the HCV NS5A replication complex inhibitor, BMS-790052, with the HCV NS3 protease inhibitor, BMS-650032, with or without peginterferon alfa-2a/ribavirin in patients infected with genotype 1 HCV who experienced previous null response to peginterferon/ribavirin therapy (Capsule Summary). In this open-label phase IIa trial, 21 patients were randomized to dual therapy with BMS-790052 60 mg once daily plus BMS-650032 600 mg twice daily or to quadruple therapy with the same doses of BMS-790052 and BMS-650032 plus peginterferon alfa-2a/ribavirin. Treatment was for 24 weeks, and patients with virologic breakthrough were eligible to add peginterferon/ribavirin therapy for up to 48 additional weeks. The primary endpoint was SVR12.

Although the patient numbers are small, all 10 patients receiving quadruple therapy for 24 weeks achieved SVR12. By contrast, only 4 out of 11 patients receiving dual therapy achieved SVR12. Patients were stratified by genotype 1 HCV subtype and no more than 2 patients with genotype 1b HCV were allowed in each treatment arm. The investigators did not state why there was a limit to the number of patients with genotype 1b HCV; however, in the dual therapy arm, both patients with genotype 1b infection achieved SVR12. The high SVR12 rate among patients with genotype 1b infection receiving dual therapy would be more convincing if there would have been more than 2 patients infected with this HCV subtype enrolled.

Graham R. Foster, FRCP, PhD: Virologic response differences according to genotype 1 subtype have been demonstrated in clinical studies with protease inhibitors as discussed previously, but there are few data as yet on the impact of HCV subtype on clinical response to NS5A inhibitors.
In an ascending dose study of another NS5A inhibitor, AZD7295, HCV RNA levels exhibited dose-dependent reductions among patients with genotype 1b HCV, but not among patients with genotype 1a or 3 infection.[36]

Stefan Zeuzem, MD: An analysis of in vitro culture systems demonstrated a lower EC50 of BMS-790052 for genotype 1b vs 1a; however, the values for both subtypes are in the subnanomolar range and the dose administered in this trial should have been effective for both subtypes.[37] Therefore, it remains an open question and further studies are needed.
In the current BMS-790052/BMS-650032 combination study, 6 out of 11 patients treated with dual therapy did not achieve undetectable HCV RNA at the end of therapy (Week 24) and experienced virologic breakthrough at various time points. A seventh patient experienced viral relapse, resulting in 4 patients (36%) with SVR12, including both patients with genotype 1b infection and 2 patients with genotype 1a infection. On the other hand, patients receiving quadruple therapy achieved an impressive 100% rate of undetectable HCV RNA at the end of treatment, and this outcome was maintained at 12 weeks after stopping therapy as mentioned previously.
At posttreatment Week 24, 1 patient in the quadruple therapy arm appeared to have detectable but not quantifiable HCV RNA; however, a retest 35 days later showed that the patient once again had undetectable HCV RNA. Therefore, the SVR rate at posttreatment Week 24 in this arm was formally 90%. The fact that all patients who received just 24 weeks of quadruple therapy were cured is a very impressive result considering that all of the patients enrolled in this trial experienced a previous null response, defined as a < 2 log10 IU/mL decline in HCV RNA after 12 weeks of peginterferon/ribavirin therapy.

Graham R. Foster, FRCP, PhD: This study represents an exciting step forward, suggesting that combining 2 potent drugs with peginterferon and ribavirin may be highly effective in some of the most challenging patients. More data are needed to clarify whether peginterferon/ribavirin are a necessary component for this patient population or whether interferon-free regimens may be possible.

Stefan Zeuzem, MD: This study and previous studies of alisporivir monotherapy in treatment-naive patients are the only public data we have suggesting that SVR can be possible with interferon-sparing regimens. Three patients with genotype 3 HCV and 1 with genotype 1 HCV have been cured and were cured with alisporivir monotherapy according to data presented to date.[38] The fact that 4 previous null responders achieved SVR with BMS-790052/BMS-650032 dual therapy provides some support for the contention that indeed interferon-sparing regimens are possible.

Paul Y. Kwo, MD: This study provides a glimpse into the future of treatment for null responders. A particularly important issue regarding these findings is that some of the most difficult to treat patients, including some null responders, are people who cannot tolerate peginterferon and ribavirin; these data lend great hope to that substantial population.
Stefan Zeuzem, MD: As yet there are no data regarding predictors of SVR to these regimens for previous null responders. The only predictor that may be assumed at this time is HCV subtype 1b; however, even this assumption is too preliminary. More data from larger trials will be needed before we can determine which patients might be appropriate candidates for an interferon-sparing regimen or whether quadruple therapy would be recommended.

Graham R. Foster, FRCP, PhD: This study provides an exciting start, but it is important to emphasize that these data are very preliminary and involve a very small number of patients. Patients may see these data and expect that 2-drug regimens will be available in the near future; however, even if these data can be confirmed in larger studies, it will be quite some time before such regimens are available. Therefore, patients with cirrhosis certainly cannot afford to wait until that time. Nonetheless, even clinicians with a strong belief in the value of interferon are beginning to consider that interferon may have a more limited future.

March 31, 2011 Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained Virologic Response in Phase II Dose-Ranging Study of Treatment-Naive Hepatitis C Patients

EASL 2011-
HCV Cured With out Peginterferon/ribavirin with 2 oral HCV drugs BMS790052+BMS650032: Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: "HCV infection can be cured without interferon & ribavirin: 2 orals BMS790052+BMS650032" - (04/02/11)

Liver Cancer

Two Liver Cancer Discoveries May Impact Hepatitis Patients
Researchers in different countries make two liver cancer discoveries, progress that could have a positive impact on people with advanced chronic Hepatitis B or Hepatitis C.
by Nicole Cutler, L.Ac.
Millions of Americans are currently living with chronic Hepatitis B or Hepatitis C, viral illnesses that can cause significant damage to the liver. Unfortunately, chronic viral hepatitis is the most prominent risk factor for developing hepatocellular carcinoma (HCC), a primary liver cancer. Extraordinarily hard to treat, hepatocellular carcinoma is one of the most perilous types of cancer possible. However, two newly released studies that examined liver cancer on molecular levels could lead to improved treatments - a potential relief to many people with advanced Hepatitis B or Hepatitis C.

Deferoxamine Shows Promise for Liver Cancer in People with Advanced Disease
Deferoxamine, a cancer drug that has an anti-proliferative effect on tumor cells, led to improvement of hepatocellular carcinoma (HCC) in 2 out of 10 patients with moderate-to-severe liver disease, according to a letter in the August 11, 2011, New England Journal of Medicine.

Hepatocellular Carcinoma After Diagnosis of Hepatitis B or C Infection
New Non-Invasive Technology Shows Promise in Shrinking Liver Tumors
Peginterferon Maintenance Therapy in Patients with Advanced Hepatitis C to Prevent Hepatocellular Carcinoma: The Plot Thickens
Watch; RF ablation alternative to surgery in early liver cancer
Metabolic syndrome increases risk of both major types of primary liver cancer


Generic Drug Makers May Soon Pay for Overseas Plant Inspections - ABC News
By (@kimcarollo)
Aug. 16, 2011

VIDEO: One of the world's largest generic drug makers is calling on its fellow manufacturers to help foot the bill for the U.S. Food and Drug Administration to conduct inspections of overseas pharmaceutical plants.

Up to 40 percent of the drugs Americans use are imported, and around 80 percent of the active ingredients in those drugs are made in foreign facilities.
The FDA only inspected 11 percent of the more than 3,700 foreign manufacturing sites in 2009, according to data from the U.S.Government Accountability Office. All manufacturing facilities in the United States, however, are subject to FDA inspection every two years.

Healthy You

The mysteries of belly fat
Health professionals are concerned about belly fat because it can trigger: heart disease, stroke, high blood pressure, diabetes, fatty liver, liver cancer, stress, depression and Alzheimer's. Scientists believe that it is the fat below the surface, called visceral fat, that really does the damage by producing hormones and chemicals that can cause heart disease and more. Also, evidence shows that deep-seated fat near an important vein that leads to the liver can transport fatty acids to the organ.

The result: high blood lipid readings. How do you know when the size of your stomach is putting you in peril? A general guideline is that woman with a waist of more than 35 inches, and a man over 40 inches, could be at more risk. As we age, most people struggle with weight. This is because metabolism slows down causing lean muscle mass to be lost, therefore burning fewer calories.

But there's more: Menopause Typically, women face the menopause phase of their lives sometime between the ages of 45 and 55. It is a profound change where a women's body produces less estrogen and progesterone. One of the results of this can be weight gain, which tends to be around the middle rather than the hips. This shift can begin even before, in the period called perimenopause....Continue reading....

Nearly Everyone Needs a Routine Vitamin D Supplement
By: MITCHEL L. ZOLER, Internal Medicine News Digital Network
NEW YORK – The vast majority of children and adults should receive a routine, daily vitamin D supplement, and this recommendation applies from age 1 year all the way up to age 70 years, Dr. Henry W. Lim said at the meeting.
The only exception is a select group of people at high risk for vitamin D inadequacy who warrant initial testing to be sure they don’t need an even higher starting dosage of the vitamin, said Dr. Lim, professor and chairman of dermatology at Henry Ford Hospital in Detroit.

Only people at risk for vitamin D inadequacy, such as breastfed infants or people with limited sun exposure, should be tested for serum vitamin D level, according to Dr. Henry W. Lim.
Dr. Lim based his recommendations on the revised dietary reference intakes for vitamin D issued by the Institute of Medicine last November, which set a recommended dietary allowance (RDA) of 600 IU/day for ages 1-70 years.
"In my opinion, testing [of serum vitamin D level] should only be done for people at high risk for vitamin D inadequacy," he said. In the group to consider for testing are breastfed infants, older adults with reduced skin synthesis of vitamin D, or people with limited sun exposure, dark skin, fat malabsorption (because vitamin D is fat soluble), or obesity.
"For the average individual [not in a high-risk group] my suggestion is to take 600 IU per day starting at age 1," Dr. Lim said in an interview. At that level, the supplement is relatively innocuous, inexpensive, and addresses the widespread vitamin D inadequacy. He did not rule out routine vitamin D supplements for children younger than 1 year, but noted that the RDA is lower.

Testing a person’s vitamin D level costs about $100, using ICD-9 code 268.9 for unspecified vitamin D deficiency. Doing that for everyone would incur a "tremendous" cost, he said. He also echoed the recent position taken by the American Academy of Dermatology that most vitamin D should come from diet and supplements, and not from sun exposure. "It is inappropriate to recommend intentional exposure to natural or artificial UV [light] for achieving an adequate vitamin D level," he said.

People at high risk for a low vitamin D level need testing to check whether their level falls as low as 10 ng/mL or even 5 ng/mL. With this degree of deficiency, the person might need a single 10,000-IU or even 20,000-IU dose to raise their level quickly. Daily supplements should not exceed 1,000-3,000 IU in children aged 8 years or younger and should not exceed 4,000 IU daily for those aged 9-70 years, Dr. Lim said.

Two types of vitamin D are available in supplement form, D2 and D3 (ergocalciferol and cholecalciferol, respectively). The vitamin D3 form is preferable because it is more effective at raising serum levels, it attaches better to vitamin D–binding protein, and it has a longer shelf life, Dr. Lim said.

He also reviewed the evidence documenting benefit from adequate vitamin D levels. He concurred with the IOM that the best evidence by far to support maintaining a minimum serum vitamin D level involves the vitamin’s effect on skeletal health. For other outcomes, the evidence is "inconsistent, inconclusive, and insufficient to inform nutritional requirements," Dr. Lim said.
Dr. Lim said that he has been a consultant to La Roche-Posay L’Oreal, Clinuvel, and Procter & Gamble and has been an investigator for Clinuvel.

World's Healthiest Foods
Food of the Week: Cucumbers
Sun, 14 Aug 2011 18:39:26


Exercising with Diabetes Complications
Mon, 15 Aug 2011 10:22:49
If you have had diabetes for a long time and have developed complications, you may have questions about whether you should be engaging in physical activity—and if so, what kind of physical activity is best for your condition.

According to Jacqueline Shahar, MEd, RCEP, CDE, a clinical exercise physiologist and manager of Exercise Services in the Joslin Clinic at Joslin Diabetes Center, patients with diabetes complications should definitely continue to find appropriate opportunties for physical activity. In the Joslin’s Easy Start program many patients have significant diabetes complications and are able to exercise regularly and safely as part of their diabetes self-management plan.
There is always some type of exercise people with complications can do. Not remaining activity can lead to developing additional complications and loss of functional capacity (the ability to do the activities of daily living).

Here are some of the more common diabetes complications and recommendations for exercise for each;

Peripheral Neuropathy
Peripheral neuropathy is nerve damage in the extremities, causing tingling, pain or loss of sensation in your toes, feet and fingers. Peripheral neuropathy increases the risk of loss of balance—and subsequently the increased risk of falling. In addition, the pain and burning can make it difficult to walk.
Exercise prescription:
Incorporate balance exercises and avoid weight-bearing activities such as walking or jogging. Good choices are the stationary bike and swimming.

Charcot Foot
Charcot Foot is a specific type of peripheral neuropathy in which there is destruction of the nerves on the bottom of the foot. The foot eventually becomes deformed and loses sensation. It is important to stay off your feet as much as possible.
Exercise prescription:
Use a stationary or arm bike, or do chair exercises using free weights in a seated position.

Proliferative Retinopathy
Proliferative retinopathy is advanced diabetic eye disease in which new, fragile cells develop on the optic disc. These new cells are prone to leakage or hemorrhage into the eye resulting in loss of vision. You may also be at risk for retinal detachment.
Any exercises that increase blood pressure should be avoided. You need to avoid lifting heavy objects and any vigorous exercise. In addition, do not perform any exercise that requires forward bending such as yoga or the valsalva maneuver [The Valsalva maneuver or Valsalva manoeuvre is performed by moderately forceful attempted exhalation against a closed airway, usually done by closing one's mouth and pinching one's nose shut. Variations of the maneuver can be used either in medical examination as a test of cardiac function and autonomic nervous control of the heart, or to "clear" the ears and sinuses (that is, to equalize pressure between them) when ambient pressure changes, as in diving, hyperbaric oxygen therapy, or aviation].
Exercise prescription:
Stick to non weight bearing exercise such as moderate intensity biking or walking in the pool. Or try slow, steady hiking, ballroom dancing or elliptical machines at low to moderate intensity.

Nephropathy is damaged to the kidneys, which eventually leads to complete kidney shutdown and the need for dialysis. With nephropathy, exercise capacity is decreased because of the buildup of waste products in the body.
Exercise prescription:
Light to moderate exercise is encouraged.

Other Issues to Consider When Exercising with Complications
Autonomic (central) neuropathyAutonomic (central) neuropathy can cause significant cardiac changes.The usual heart rate guidelines for exercise don’t apply. Instead use the talk test to determine if you are exercising at an acceptable level. In addition, if you have autonomic neuropathy, you may no longer experience the symptoms of low blood glucose and need to check your blood glucose more frequently.
Foot ulcer or foot deformity—non weight-bearing exercises are preferred as well as keeping the feet clean dry. You should avoid swimming,
The Talk Test
Light intensity exercise—you can sing or whistle while exercising
Moderate intensity exercise—you can talk while exercising
High intensity exercise—you can’t talk
3 Things to Remember When You Exercise with Diabetes!
It is important to check with your health care provider before starting any exercise program.
Always check your blood glucose before and after any exercise routine.
Making an appointment with an exercise physiologist can be very helpful if you have any complications of diabetes.


Hot Weather Takes Toll on Medication
Mon, 15 Aug 2011 21:49:30
The recent heat wave may have taken a toll on your medication. That’s what reporter Walecia Konrad learned after her son’s allergy medication stopped working after being exposed to high temperatures on a family vacation at the lake.
No drug should be exposed to temperatures higher than 86 degrees. Some days the bathroom at our vacation house and certainly the trunk of the car were well above that mark….