September 11, 2012

The White House

Office of the Press Secretary

For Immediate Release August 31, 2012

NATIONAL ALCOHOL AND DRUG ADDICTION RECOVERY MONTH, 2012

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

Every day, millions of Americans with substance use disorders commit to managing their health by maintaining their recovery from drug or alcohol addiction. People in recovery are not strangers: they are our family members, friends, colleagues, and neighbors. During National Alcohol and Drug Addiction Recovery Month, we recognize their strength and resilience. In partnership with Americans in recovery, let us rededicate ourselves to combatting prejudice surrounding addiction, removing barriers to recovery, and standing with all those seeking lives free from substance use.

My Administration is committed to advancing evidence based recovery solutions. Over the past 3 years, we have worked to strengthen substance abuse prevention and treatment programs, and to support Americans in recovery. We have taken steps to identify and remove laws, policies, and practices that impede recovery. And as part of our 2012 National Drug Control Strategy, we are promoting early intervention and taking action to break the cycle of drug abuse and incarceration.

Drug and alcohol abuse continue to take a tragic toll on millions of lives across our country. Yet, while more remains to be done, men and women across our country are making great strides. This month, let us encourage their progress, celebrate the transformative power of recovery, and thank the many Americans who, often strengthened by their own experiences, are working to improve the health and safety of our communities.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2012 as National Alcohol and Drug Addiction Recovery Month. I call upon the people of the United States to observe this month with appropriate programs, ceremonies, and activities.

IN WITNESS WHEREOF, I have hereunto set my hand this thirty first day of August, in the year of our Lord two thousand twelve, and of the Independence of the United States of America the two hundred and thirty-seventh.

BARACK OBAMA

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Vaccine Trial Reveals Weak Spots in HIV's Armor

vaccine-trial-reveals-weak-spots-hiv-armor_1

An AIDS vaccine has been a major goal of researchers for two decades. Image: Karen Kasmauski/Science Faction/Corbis

A new analysis identifies targets for an immune response that could improve AIDS vaccines

By Ewen Callaway and Nature magazine

From Nature magazine

HIV is finally revealing its weak spots to researchers, bringing an effective vaccine against AIDS closer to reality.

A paper published in Nature today1 sheds light on how a vaccine can turn the immune system against the invading virus and so offer protection from infection. The results are also being presented at the AIDS Vaccine 2012 conference in Boston, Massachusetts, this week.

The findings help to explain the results from a clinical trial of an AIDS vaccine that have puzzled researchers since they were published three years ago2. The trial, called RV144, was the first to score a success and see a reduction in HIV infections. But the vaccine’s relatively low response rate of 31% left researchers scratching their heads.

A clue emerged last year with the revelation that those who responded to the vaccine and fended off HIV tended to produce antibodies against a specific part of the virus's protein shell called the V1/V2 loop3. The study published today goes a stage further, showing that the people who were vaccinated yet still contracted HIV had been infected by viruses that had mutations in the the V2 portion.

“This is a really good paper,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. “It adds to the growing body of information indicating that an immune response against components of the V1/V2 loop is important in vaccine-induced protection against infection.”

The team behind the study was led by Morgane Rolland and Jerome Kim at the US Military HIV Research Program in Silver Spring, Maryland. They examined 936 HIV sequences collected from 44 trial participants who received the vaccine and became infected, and 66 people who got the placebo. The trial was randomized, so any systematic differences in the viral DNA sequences between the two groups will be due to selective pressure by the vaccine in favour of viruses that do not match the vaccine, Rolland says.

The team identified two mutations that seemed to be linked to vaccination success. Both were located in the V2 region of the V1/V2 loop. Rolland and Kim's team compared the rates of infection with viruses whose sequence varied at these two sites between people who received the vaccine and those who got a placebo. People who received the vaccine were 80% less likely to be infected by viruses with these mutations, compared to people who got a placebo. The implication is that the vaccine triggered an immune response that prevented certain viruses from infecting them, and only viruses with different sequences at those two sites had a good chance of creating an infection.

Another study, led by researchers at NIAID, to be presented at the vaccine conference this week analysed the molecular structure of antibodies from the blood of vaccinated people and found that some of their antibodies recognized the same amino acids in the V2 region.

The question facing vaccine developers now is how to improve the response against V2. A vaccine similar to that used in RV144 is set to be tested in South Africa and among men who have sex with men in Thailand in two trials that will begin around 2014. Scientists hope that giving a booster within a year of the first jab and a new adjuvant will lead to a stronger and longer-lasting response against HIV and its V2 region, says Kim who is helping to design the trials.

Mounting a response against V2 “isn’t the whole answer to vaccine protection”, says Fauci, but “you can be darn sure people are going to figure out how to rev it up”.

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[Date: 2012-09-11]

A team of scientists has used a new technology to uncover three genetic regions associated with primary biliary cirrhosis (PBC), a chronic and progressive disease of the liver.

The aim of the study was to survey more thoroughly regions of the genome known to underlie other autoimmune diseases, to discover if they also play a role in PBC susceptibility.

Scientists used a DNA microchip called Immunochip in their tests: the advantage of Immunochip over genome-wide technologies is that it focuses only on regions of the genome known to be associated with an autoimmune disease, and thus captures more of the genetic variation within these regions. Immunochip can therefore be used to more thoroughly test these key candidate genes for association to a whole-host of immune-related traits, and to identify low-frequency and rare genetic variants associated with disease that would likely be missed by a microarray covering a broader range of genetic regions.

Writing in the journal Nature Genetics, the researchers outline how they identified three genetic regions associated with PBC, increasing the number of known regions associated with the disorder to 25.

By combining the results from this survey with details of gene activity from a database called ENCODE, they were able to identify which cell types are most likely to play a role in PBC.

PBC affects approximately one in a thousand women over the age of 40. The condition is characterised by inflammation in the bile ducts that blocks the flow of bile, damaging the liver cells and causing further inflammation and scarring. In severe cases, this results in the need for a liver transplant.

As there is currently no cure for PBC, treatment is focused on slowing down the progression of the disease and treating any symptoms or complications that may occur. The biological pathways underlying primary biliary cirrhosis are poorly understood, although autoimmunity, where the body attacks its own cells, is known to play a significant role.

Co-senior author of the study Dr Carl Anderson from the Wellcome Trust Sanger Institute comments: 'Previous genetic screens have identified 22 regions of the genome underlying PBC risk, and many of these are known to play a role in other autoimmune diseases, such as multiple sclerosis and type I diabetes. Using the Immunochip we were able to perform a much more thorough screen of the genomic regions previously associated with other autoimmune diseases. This resulted in us identifying a further three regions involved in PBC risk and identifying additional independent signals within some of those we already knew about.'

The hope is that these results could lead to the development of a new therapeutic approach for the treatment of PBC.

For more information, please visit:
Wellcome Trust Sanger Institute:
http://www.sanger.ac.uk/

Category: Miscellaneous
Data Source Provider: Wellcome Trust Sanger Institute
Document Reference: Liu, J. Z. et al., Dense fine-mapping study identifies novel disease loci and implicates coding and non-coding variation in primary biliary cirrhosis risk, Nature Genetics, 2012. doi:10.1038/ng.2395
Subject Index: Medicine, Health; Life Sciences; Scientific Research

RCN: 35009

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BMS-logo

Company will share BMS-986094 data with other companies developing similar hepatitis C drugs to inform patient safety measures

Thursday, August 23, 2012 6:20 pm EDT

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) announced today that the Company has discontinued development of BMS-986094 (formerly known as INX-189), a nucleotide polymerase (NS5B) inhibitor that was in Phase II development for the treatment of hepatitis C. This decision was made in the interest of patient safety, based on a rapid, thorough and ongoing assessment of patients in a Phase II study that the Company voluntarily suspended on August 1, 2012. The U.S. Food and Drug Administration (FDA) subsequently placed the compound on clinical hold.

The initial case of heart failure, which was the basis for halting the study, subsequently resulted in death. The Company is working in close collaboration with the FDA and clinical study investigators to conduct ongoing, comprehensive assessments and close follow-up of all BMS-986094 study patients. To date, nine patients have been hospitalized, including the initial patient; two patients remain hospitalized. While the cause of these unexpected events, which involve heart and kidney toxicity, has not been definitively established, the Company has determined that it is in the best interest of patients to halt development of BMS-986094.

“The decision to halt development of BMS-986094 has been guided by our overriding interest in protecting patients,” said Elliott Sigal, M.D., Ph.D., Executive Vice President and Chief Scientific Officer, Bristol-Myers Squibb. “In the interest of all patients participating in hepatitis C clinical studies, and in cooperation with the FDA, we will make relevant information on BMS-986094 available to inform the development of other investigational compounds to treat hepatitis C. We will also work expeditiously to share the results of our further investigations more broadly in the medical and scientific community.”

Bristol-Myers Squibb is committed to investigating this safety issue further, including studies to evaluate the potential mechanism of this toxicity. The Company will continue close monitoring and follow-up of patients who have received BMS-986094 across all studies.

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 about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

 

Contact:

Bristol-Myers Squibb Company
Media:
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
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John Elicker, 609-252-4611
john.elicker@bms.com
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Timothy Power, 609-252-7509
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Discriminatory Donor Policies Substitute Stereotypes for Science

Blood Shortage

People rest on tables as they give blood for the Red Cross in Princeton, New Jersey. The lifetime deferral policy for MSM blood donors has been called into question for years because of its lack of a scientific basis and its failure to reflect the current technologies used by blood donation centers across the country. SOURCE: AP/Mel Evans

By Andrew Cray | September 11, 2012

Every day in the United States, 43,200 people—one every two seconds—need life-saving blood transfusions. In that same 24 hours, 18 people will die while waiting for a donor organ, with the gap between donated organs and those on the waitlist growing every year. Our country is in the midst of what could only be described as a critical shortage of the blood, tissue, and organ donations that sustain and improve the lives of patients across our country.

Yet the Department of Health and Human Services’ policies on donor eligibility prevent donation by gay men because of outdated assumptions that are decades out of step with medical science. These policies harm patients who would benefit from the department modernizing these standards, which amount to little more than discriminatory relics of the past. As noted by Rep. Mike Quigley (D-IL), “Equality for the LGBT community is closer than ever, but outdated and discriminatory policies … must evolve to match advancements in science and technology.”

Thirty years ago The New York Times ran an article describing “a matter of urgent public health and scientific importance.” The urgent matter was the appearance of a new disease, then known as gay-related immunodeficiency, or GRID, and now known as the human immunodeficiency virus, or HIV. That same year, several blood transfusion recipients who did not match the pattern for transmitting GRID were diagnosed with the disease, and researchers later began to understand the role that blood transfusion and other transfer of human tissues played in the spread of the disease.

These events culminated in the Department of Health and Human Services developing the first of several policies that would restrict gay men from donating life-saving blood, tissue, and organs. This initial policy on blood donor eligibility—requesting voluntary deferral by “sexually active homosexual and bisexual men with multiple partners”—was the most plain of the donation policies that would evolve over the next several decades in targeting donors for exclusion on the basis of their sexual orientation.

But these deferral policies reveal more than just a problematic reaction to the early stages of the HIV epidemic in the United States. They also offer a glimpse into the persistent discriminatory motivations that underlie current limitations on blood, tissue, and organ donation by men who have sex with men, or MSM. These policies, which have endured despite significant advances in testing, screening, and transmission prevention, are vestiges of antiquated bias and misinformation, and no longer align with the progress made in medical technology and public health policy.

Blood donation

The ban on MSM blood donation is the most well-known of the U.S. donation policies that discriminate against men who have sex with men. This policy, modified from the original voluntary deferral established in the 1980s, has grown to require permanent deferral by any man who has had sex with another male, even once, since 1977. By contrast, non-MSM donors who are also considered to be high risk are often permitted to donate with little or no deferral period at all. A person who has heterosexual sexual contact with a person who has used injection drugs, for example, is only prohibited from donating blood for 12 months.

The lifetime deferral policy for MSM blood donors has been called into question for years because of its lack of a scientific basis and its failure to reflect the current technologies used by blood donation centers across the country. The technological developments of the past decade have made blood testing so effective that the probability of HIV transmission through blood transfusion is only one in 1.5 million—less than half the risk posed in the mid-1990s.

The use of a more precise blood donor questionnaire could further reduce this risk by asking questions about sexual practices, including the use of barrier contraceptives and the sexual contact a potential donor has participated in. This would reflect the actual variation in transmission risk based on the type of sexual contact a potential donor has had, as well as the reduction in that risk through the use of condoms.

While the Department of Health and Human Services recently proposed a pilot study designed to explore alternative donation deferral policies for men who have sex with men—a move toward evidence-based donor screening practices—the blood donation ban remains in effect. This in turn aggravates an ongoing blood shortage, which could be drastically reduced or even eliminated by lifting the MSM donation ban, potentially saving an additional 650,000 lives each year.

Tissue and tissue product donation

The same arm of the Food and Drug Administration that regulates blood donation—the Center for Biologics Evaluation and Research—also sets eligibility standards for donors of tissue and tissue products. Examples of the types of tissue that the center regulates include bone, skin, heart valves, tendons, and sperm.

The conversation about tissue donation policies—specifically sperm donation—has been reignited over the last month with a slew of bloggers, doctors, and even television shows criticizing the FDA’s policy. But even though the last month has seen increased talk about tissue donor standards, industry guidance put in place by the Center for Biologics Evaluation and Research on tissue donation by gay men and other men who have sex with men has been in place for five years.

The restrictions on tissue donor eligibility for men who have sex with men, however, are less restrictive than those on blood donor eligibility. Rather than a lifetime prohibition on donation, men who have had sex with another man in the preceding five years are ineligible to donate, effectively imposing a five-year abstinence requirement for potential gay donors.

Though less restrictive, tissue donor standards still discriminate against men who have sex with men by limiting their eligibility more tightly than other prospective donors who are considered to be high risk. As with blood donation, for example, a person who has heterosexual sexual contact with an injection drug user is only prohibited from donating blood for 12 months.

Tissue donor eligibility standards propagate the same outdated stigmatizing message about gay men as the blood donation ban, and still without scientifically valid rationale. Furthermore, tissue donation standards applying to sperm donors adversely affect lesbian, gay, bisexual, and transgender families. Some gay women prefer to receive sperm from gay donors, and prohibiting donation for a significant number of these men puts additional barriers in place to creating families, at the cost of the autonomy and the preferences of parents.

Organ donation

The last and probably least well-known discriminatory MSM donation policy relates to organ donor eligibility. Organ donation standards are set by a different branch of the Department of Health and Human Services than blood and tissue policies—the Health Resources Services Administration, which sets criteria for donors of vascularized human organ transplants, including the kidney, liver, heart, lungs, and pancreas.

Organ donor eligibility standards represent the current best balance, though not ideal, between maintaining a safe supply of donor organs while treating men who have sex with men fairly when compared with other potential donors. Currently, organ procurement organizations are required to obtain a medical history for potential donors to identify factors associated with increased risk for disease transmission, including HIV transmission. If a potential donor meets criteria set forth in the current Public Health Service guidance, the organ procurement organization must communicate that information to transplant programs receiving organs from the donor. The guidance classifies men who have had sex with another man in the preceding five years as high risk.

A second policy requires that transplant programs obtain informed consent prior to transplantation of an organ when, in that transplant program’s medical judgment, the donor has a recognized increased risk for disease transmission. As a result of these two policies, sexually active MSM organ donors are not subject to any deferral requirement or donation ban, but the transplant programs receiving the organs, and possibly the organ transplant recipient, must be informed of the purported increased risk factors of the donor.

Of course, policies based on the presumption that men who have sex with men pose increased risk miss the mark by failing to recognize the variation in risk between kinds of sexual contact, both for MSM and non-MSM potential donors. And similar to practices in blood donor screening, MSM organ donors are not asked about use of condoms, once again failing to acknowledge the drastically reduced risk of disease transmission associated with safer sex practices.

Unique to the context of organ donation is the treatment of HIV-positive donors and transplant recipients. Individuals at high risk for HIV, as well as individuals who are HIV positive, can receive organ transplants. But a recent study suggests that approximately 500 HIV-positive people in need of replacement livers and kidneys could receive them each year if organ donations by HIV-positive donors were also permitted. This change could potentially provide transplanted organs to every HIV-positive transplant candidate on the waiting list.

For HIV-positive potential donors, however, legislative roadblocks prevent the donation of potentially life-saving organs. Regulations implementing the National Organ Transplant Act of 1984, passed at the height of antigay rhetoric surrounding HIV/AIDS, require the adoption of standards for preventing the acquisition of organs from individuals known to be infected with HIV. The act thus prohibits the acquisition of organs from HIV-positive donors, while hundreds of HIV-positive people in need of donated organs languish on long transplant waitlists.

The discriminatory roots of this ban are underscored by the fact that HIV transmission policies are significantly more restrictive than policies addressing other infections that can also be transmitted during the transplantation process. Individuals who test positive for Hepatitis C, for example, are permitted to donate organs to patients who also have Hepatitis C.

Donation policies need to be based in science, not in discriminatory bias

Balancing the safety and adequacy of the nation’s donated blood, tissue, and organs is undoubtedly a pressing health policy challenge. But the use of policies that discriminate against gay men, resting on presumptions that are decades behind science, do not reflect the best solution. Instead, the donation limitations for men who have sex with men promote homophobic attitudes and inaccurate assumptions about gay men that drive the HIV epidemic and prevent progress in the development of evidence-based policies and standards.

Ensuring improved public health and safety will require full use of advances in medical technology, the development of donor screening standards that accurately measure risk equally among all potential donors, and dedication to public policy that progresses beyond outdated biases.

Andrew Cray is a Research Associate for LGBT Progress at the Center for American Progress.

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Print: Katie Peters (economy, education, and health care)
202.741.6285 or kpeters1@americanprogress.org

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Source

Allison RD. J Infect Dis. 2012;206:654-661.

September 6, 2012

The study, which began enrollment in August 1990, included 738 volunteer blood donors who tested positive for hepatitis C antibodies. Confirmation testing was done using third-generation recombinant immunoblot assays (RIBA). The donors were interviewed by a physician about their histories, including illicit drug use. Liver biopsy specimens were taken from 185 patients with RIBA-confirmed hepatitis C.

Among the 738 volunteers, 469 had hepatitis C confirmed using RIBA. On multivariate analysis, the most significant risk factor was injection drug use, with an OR of 35 (95% CI, 10.4-218), followed by receiving a blood transfusion before 1991, with an OR of 9.9 (95% CI, 5.6-18.3). Intranasal cocaine use was also a significant risk factor, with an OR of 6.4 (95% CI, 3.8-11.2). In a subset of intranasal cocaine users who denied injection drug use and blood transfusion, the OR was 8.5 (95% CI, 4.9-15.1).

Among those who were confirmed with RIBA, 384 had hepatitis C virus RNA. From these patients, 33% of liver biopsy specimens showed no fibrosis, 52% had mild fibrosis, 12% had bridging fibrosis and 2% had cirrhosis.

“Identification of silent HCV carriers and access to treatment remain major public health hurdles, but among treated subjects, the number who will not achieve a sustained virologic response has been reduced dramatically with the recent licensure of protease inhibitors,” the researchers wrote. “Since the majority of HCV-infected individuals will not be treated in the near term, continued long-term follow-up is critically needed to provide better estimates of clinical and histologic outcomes after 3 or more decades of HCV infection."

Disclosure: The researchers report no relevant financial disclosures.

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Challenges remain in reaching 100% cure rate in HCV

September 10, 2012

SAN FRANCISCO — More than 20 years after hepatitis C was first discovered, its incidence has increased significantly, but there have also been significant advances in its treatment, according to a keynote lecture by Charles M. Rice, PhD, at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Rice, the Maurice R. and Corinne P. Greenberg Professor in Virology at The Rockefeller University, discussed how far we’ve come in identifying and treating hepatitis C, but also emphasized that challenges remain to reach the 100% cure rate goal.

“The treatment for hepatitis C is going to get more complicated before it gets simple,” Rice said. “The good news is that the field is changing on a daily basis.”

Burden of HCV

Hepatitis C is a global problem, affecting more than 130 million people worldwide. Although its incidence in the United States has declined since 2007, the mortality associated with hepatitis C has surpassed that of HIV and it is expected to continue to rise. In fact, it is not expected to peak until about 2020, Rice said.

According to Rice, one of the reasons that hepatitis C has taken a back seat to other infectious diseases is that it is initially asymptomatic. There is a slow progression to symptomatic disease, so most people do not know that they are infected.

“We are unable to predict which patients are going to go on to develop liver cancer or cirrhosis, or which people are going to live 50+ years and ultimately succumb to another illness,” Rice said. “This is a frustrating aspect of hepatitis C, for both patients and clinicians.”

Since its discovery in 1989, there have been several goals related to hepatitis C. One, cleaning up the blood supply, has been successfully reached in the United States. An ongoing goal is educating high-risk people and another goal, treatment success, is dependent on identifying people who are infected.

“Many people don’t know of their infection until they already have severe liver damage,” Rice said. “Less than 50% of people with hepatitis C know that they have it.”

As for research of hepatitis C, there are challenges. The first is that the virus is difficult to replicate in cell cultures. The ideal model for research is the chimpanzee model, which is the most important model for all hepatitis viruses. The problem is that it is very difficult and expensive to work with. There is not yet a small animal model that is ideal for researching the virus.

Despite these challenges, the good news is that successful treatment does represent a cure in most cases, Rice said. Sustained virologic response is defined as having undetectable virus at 6 months after treatment. In 95% of the cases that achieve that, the response is durable.

Treatment response

Treatment for hepatitis C has also improved since interferon alfa was approved by the FDA for treatment. The addition of ribavirin to interferon significantly improved the rate sustained virologic response, though alone, ribavirin had no effect. Later, the introduction of pegylated interferon also demonstrated a benefit.

Within the past year, the most significant addition to the treatment armamentarium has been protease inhibitors, boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex).

However, although we are approaching a 75% cure rate with the protease inhibitors, they are associated with adverse effects. Patients who are receiving these therapies, along with pegylated interferon and ribavirin, are often hospitalized, Rice said. The drugs are also expensive.

“We’re at a stage where we have good proof of concept that these antivirals can improve therapy, but we still have a long way to go,” Rice said.

Eventually, the goal is to find treatment regimens that do not include pegylated interferon, and if possible, regimens that include neither pegylated interferon or ribavirin, Rice said. One promising option is the combination of daclatasvir (Bristol-Myers Squibb) and GS-7977 (Gilead), which resulted in a cure rate of 100% just 4 weeks after going off treatment, according to a study presented at the European Association for the Study of Liver Disease this year.

“This is very exciting,” Rice said. “We’ve gone from the mystery virus discovered in the mid-80s, to having diagnostics in place in the early 90s, and now approaching a 75% cure. The question is how do we get to a 100% cure? This is the ultimate goal.”

For more information:

Rice C. Emerging New Issues in the Management of Hepatitis C Infection. Presented at: 52nd ICAAC; Sept. 9-12, 2012; San Francisco.

Disclosure: Dr. Rice reports financial relationships with Apath, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, iTherX, Merck, Novartis and Vertex Pharmaceuticals.

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Warning over sirolimus in HCV-positive liver transplantation

By Kirsty Oswald, medwireNews Reporter

10 September 2012

Liver Transpl 2012; 18: 1029–1036

medwireNews: Sirolimus, whether given at the time of liver transplantation (LT) or after, is associated with poorer outcomes in patients with hepatitis C virus (HCV) infection compared with those who do not take the immunosuppressant, shows a US study.

The findings help provide important information on the controversial use of mammalian target of rapamycin (mTOR) inhibitors as primary immunosuppressants after LT.

"The results of this analysis suggest that mTOR inhibitors should be used with great caution in LT recipients with HCV infections," write Michael Charlton (Mayo Clinic and Foundation, Rochester, Minnesota, USA) and colleagues in Liver Transplantation.

The study included 26,414 transplant patients, included in the Scientific Registry of Transplant Recipients. Overall, 12,589 had an underlying HCV infection and sirolimus was prescribed at discharge in 1685 patients. Patients were followed up at 6 months and annually thereafter.

Multivariate analysis showed that patients with HCV were 26% more likely to die within 3 years if they were given sirolimus at discharge compared with those who were not. However, in HCV-negative patients, there was no significant association between sirolimus and risk for mortality.

In comparison, the calcineurin inhibitor, tacrolimus was associated with a 26% reduction in the risk of 3-year mortality in HCV-positive patients and a 44% reduction in HCV-negative patients.

To minimize the likelihood that their findings were due to sirolimus being prescribed in the most high-risk patients, the authors conducted a propensity analysis, controlling for factors known to affect posttransplant survival. However, the influence of sirolimus on 3-year mortality persisted.

The authors also found that patients taking sirolimus for longer than a year and those that began treatment more than a year after surgery had reduced survival compared with those who took the immunosuppressant immediately after surgery but for less than a year.

In an accompanying editorial, Parul Agarwal and Michael Lucey (University of Wisconsin, Madison, USA) say that the study "sounds an important note of warning regarding the use of mTOR inhibitors in HCV-infected LT recipients."

However, they caution that the study has significant limitations and say that further research is needed.

"A greater understanding of the relative impact of available immunosuppressive agents on key posttransplant outcomes is one of the most pressing needs of the LT community," the authors concur.

medwireNews (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

Free abstract

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Acupuncture Does Help for Chronic Pain

34673

By Nancy Walsh, Staff Writer, MedPage Today

Published: September 10, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Acupuncture provides more relief from various types of chronic pain than does usual care and should be considered a valid therapeutic option, the authors of a meta-analysis concluded.

For back and neck pain, osteoarthritis, and chronic headache, pain scores among patients treated with acupuncture were 0.23 (95% CI 0.13 to 0.33), 0.16 (95% CI 0.07 to 0.25) and 0.15 (95% CI 0.07 to 0.24) standard deviations below the scores for patients receiving sham acupuncture (P<0.001 for all), according to Andrew J. Vickers, DPhil, of Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.

But effect sizes were even larger when acupuncture was compared with no acupuncture, with scores of 0.55 (95% CI 0.51 to 0.58), 0.57 (95% CI 0.50 to 0.64), and 0.42 (95% CI 0.37 to 0.46) standard deviations lower (P<0.001 for all), the researchers reported online in Archives of Internal Medicine.

Acupuncture is recognized as having certain physiologic effects that can contribute to pain relief, but no plausible mechanism has been identified that could lead to long-term benefits for chronic pain, with the result that the treatment remains "highly controversial," according to the researchers.

Many controlled studies of acupuncture for pain have been published, but quality has been inconsistent and reliability has been questioned.

To provide more clarity about the effects of acupuncture on pain, Vickers and colleagues conducted an individual patient data meta-analysis based exclusively on high quality randomized trials.

Included trials required pain of at least a month's duration, with the primary endpoint being assessed at least a month after acupuncture treatment began.

The researchers were able to acquire the original raw data for 29 studies that included 17,922 patients.

To explain the clinical significance of the effect sizes found in the meta-analyses, they noted that a typical pain score in a clinical trial might be 60 on a 100-point scale.

If the standard deviation was assumed to be 25, scores after treatment could be 30 for true acupuncture, 35 for sham acupuncture, and 43 for no acupuncture, they estimated.

Another way of looking at this would be that if response was categorized as a decrease in pain of 50%, response rates would be 50% for true acupuncture compared with 42.5% and 30% for sham acupuncture and no acupuncture, respectively.

"The average effect, as expressed in the meta-analytic estimate of approximately 0.5 [standard deviations], is of clear clinical relevance whether considered either as a standardized difference or when converted back to a pain scale," Vickers and colleagues stated.

They noted that there was significant heterogeneity in a number of the analyses, particularly in the control groups of the various studies.

In some trials, for example, patients in the usual-care control groups were permitted to have rescue analgesics only, while in other studies there were exercise and physical therapy programs.

Moreover, in the sham acupuncture trials, different approaches were permitted, such as using nonpenetrating needles and using non-needle methods such as inactive electrical stimulation.

Other limitations of the meta-analysis included the possibility of bias when acupuncture was compared with no acupuncture and the use of different endpoints in some trials.

Nonetheless, the authors stated that their findings should be considered "both clinically and scientifically important."

They noted that many clinicians would be unwilling to refer a patient for acupuncture if the effects derived only from the nonspecific belief on the part of the patient that the treatment would help.

But the finding that true acupuncture had significantly greater effects than the sham procedure indicates that the effects of the procedure do extend beyond placebo, they observed.

This is "of major importance for clinical practice," meaning that acupuncture should be considered "a reasonable referral option for patients with chronic pain," they stated.

In an invited commentary accompanying the meta-analysis, Andrew L. Avins, MD, of Kaiser-Permanente in Oakland, Calif., argued that the benefits indeed were primarily those associated with the placebo effect, because the pain relief was so much greater when acupuncture was compared with usual care than when compared with the sham procedure.

But whether that should mean acupuncture has no value for patients, largely because of uncertainty as to its mechanisms of action, is a crucial concern, he pointed out.

"The ultimate question is: does this intervention work (or, more completely, do its benefits outweigh its risks and justify its cost)?" Avins wrote.

For acupuncture, the current meta-analysis offers "some robust evidence" that acupuncture does provide greater chronic pain relief than usual care, mechanisms of effect aside.

"Perhaps a more productive strategy at this point would be to provide whatever benefits we can for our patients, while we continue to explore more carefully all mechanisms of healing," Avins concluded.

Funding for this work was provided by the National Center for Complementary and Alternative Medicine, the Samueli Institute, and the U.K. National Institute for Health Research.

Authors and editorialist all reported no financial disclosures.

Primary source: Archives of Internal Medicine
Source reference:
Vickers A, et al "Acupuncture for chronic pain: individual patient data meta-analysis" Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.3654.

Additional source: Archives of Internal Medicine
Source reference:
Avins A "Needling the status quo" Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.4198.

Source