December 31, 2010

December 30, 2010 09:12 AM Eastern Time

NASA Developed Bioreactor Could be Huge Boost for Company’s Celulas Genetica Subsidiary

HOUSTON--(BUSINESS WIRE)--Emerging Healthcare Solutions, Inc. (PinkSheets:EHSI) revealed today that their new License Agreement with Regenetech specifically allows the Company to use NASA’s Intrifuge Rotary Cell Culture System in The People’s Republic of China. EHSI has been granted a sub-license for the NASA Intrifuge Rotary Cell Culture System from Regenetech in the License Agreement. What differentiates the NASA technology is the addition of simulated weightlessness in the Rotary Cell Culture System or “bioreactor”. Cell cultures, including stem cells, grown inside the bioreactor look and function much closer to human cells grown within the body than cell cultures grown in Petri dishes. EHSI has also purchased an Intrifuge Rotary Cell Culture System.

This new license is essential to new stem cell research planned by Celulas Genetica, EHSI’s biotech division, including its current endeavor to develop a revolutionary new cure for liver disease known as the Rutherford Procedure. Celulas Genetica is currently planning to test this new procedure in China.

The Rutherford Procedure is a groundbreaking organ regeneration treatment that utilizes proton-beam technology to destroy diseased organ tissue for regeneration using adult stem cells. During the procedure, proton therapy will be used to destroy scar-tissue cells in the liver using high-energy proton beams, a non-invasive treatment proven to minimize damage to healthy tissues and to eliminate the side effects (including nausea) of traditional radiation therapy. As the scar tissue is systematically destroyed by the proton therapy, a catheter will deliver the patient’s own cultured stem cells directly to the patient’s liver through the bloodstream. As more and more diseased tissue is destroyed, these cultured stem cells could help regenerate the patient’s damaged, cirrhotic liver into a healthy, functioning organ once more.

Celulas Genetica purchased a license to develop and market the Rutherford Procedure earlier this month, a day before EHSI announced the company’s acquisition. Celulas Genetica is only the latest outpost in Emerging Healthcare Solutions’ global footprint. In addition to its Houston headquarters, the company also maintains business offices in Frankfurt, Germany and Warsaw, Poland.

See more about Celulas Genetica at: http://www.thestemcellgroup.com/

EHSI invests in technology developed to compete in the medical research industry alongside Amyris Inc. (NASDAQ:AMRS), Quest Diagnostics Inc. (NYSE:DGX), Laboratory Corporation of America (NYSE:LH) and Amgen (NASDAQ:AMGN).

About Emerging Healthcare Solutions, Inc.

Emerging Healthcare Solutions, Inc. invests in and participates in the profits of emerging breakthrough medical technologies. The Company believes the secret of leveraging future value for its shareholders is the proper timing of its investment in promising new medical technologies. EHSI aims to capture future profits of promising new medical technologies by investing in these technologies at the inflection point of product development. We believe this model will deliver long-term positive results for our investors.

For more information about EHSI, please visit http://www.emerginghealthcaresolutionsinc.com/.

Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This news release contains forward-looking information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements that include the words "believes," "expects," "anticipate" or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of the company to differ materially from those expressed or implied by such forward-looking statements. In addition, description of anyone's past success, either financial or strategic, is no guarantee of future success. This news release speaks as of the date first set forth above and the company assumes no responsibility to update the information included herein for events occurring after the date hereof.

Contacts
Emerging Healthcare Solutions, Inc.
Cindy Morrissey, 713-821-1486
President and CEO

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Published on: 2010-12-31

Hepatocellular carcinoma (HCC) is the fifth most common cancer and advanced hepatic fibrosis is a major risk factor for HCC. Hepatic fibrosis including liver cirrhosis and HCC are mainly induced by persistent hepatitis B or C virus infection, with approximately 500 million people infected with hepatitis B or C virus worldwide.

Furthermore, the number of patients with non-alcoholic fatty liver disease (NAFLD) has recently increased and NAFLD can progress to cirrhosis and HCC. These chronic liver diseases are major causes of morbidity and mortality, and the identification of non-invasive biomarkers is important for early diagnosis.

Recent advancements in quantitative and large-scale proteomic methods could be used to optimize the clinical application of biomarkers. Early diagnosis of HCC and assessment of the stage of hepatic fibrosis or NAFLD can also contribute to more effective therapeutic interventions and an improve prognosis.

Furthermore, advancements of proteomic techniques contribute not only to the discovery of clinically useful biomarkers, but also in clarifying the molecular mechanisms of disease pathogenesis by using body fluids, such as serum, and tissue samples and cultured cells. In this review, we report recent advances in quantitative proteomics and several findings focused on liver diseases, including HCC, NAFLD, hepatic fibrosis and hepatitis B or C virus infections.

Author: Hirofumi UtoShuji KanmuraYoichiro TakamiHirohito Tsubouchi

Credits/Source: Proteome Science 2010, 8:70

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Annals of Internal Medicine
December 20, 2010

"Annual HIV screening and counseling leading to 50% behavior reduction in infected persons, along with 90% ART initiation in symptomatic patients, reduces new infections to fewer than 35 000 per year.....expanding HIV screening and treatment could prevent 200 000 to 300 000 infections over 20 years or approximately 17% to 24% of new infections, adding up to 6.8 million QALYs to the population. To prevent 24% of new infections, routine HIV screening would need to occur annually, with antiretroviral treatment available for essentially all symptomatic patients......Our third finding is that the net benefit of implementing both interventions is greater than the sum from implementing each program individually. A substantial increase in HIV screening or treatment could prevent 95 000 or 198 000 new infections, respectively, whereas a combination program could avert 300 000 infections (an increase of 7000 infections prevented or 2%).....Finally, we find that expanded utilization of ART (to 75% or 90% initiating ART at a CD4 cell count less than 0.350 x 109 cells/L) is very cost-effective, as is 1-time screening of low-risk groups and annual screening of high-risk groups. Combination strategies prevent more HIV infections and increase QALYs more than either individual strategy. As noted, our analysis specifically accounts for the effect of combination screening and treatment on population-wide HIV transmission, which is a strength of our modeling framework. As routine HIV screening for adults increases across health care settings due to recently revised CDC guidelines (3), it is important to ensure that ART utilization increases at a concomitant rate"

Abstract

Background: Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral therapy (ART) are limited, and all eligible persons are not currently receiving treatment.

Objective: To evaluate the effects on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to reduce risk behavior.

Design: Dynamic mathematical model of HIV transmission and disease progression and cost-effectiveness analysis.

Data Sources: Published literature.

Target Population: High-risk (injection drug users and men who have sex with men) and low-risk persons aged 15 to 64 years in the United States.

Time Horizon: Twenty years and lifetime (costs and quality-adjusted life-years [QALYs]).

Perspective: Societal.

Intervention: Expanded HIV screening and counseling, treatment with ART, or both.

Outcome Measures: New HIV infections, discounted costs and QALYs, and incremental cost-effectiveness ratios.

Results of Base-Case Analysis: One-time HIV screening of low-risk persons coupled with annual screening of high-risk persons could prevent 6.7% of a projected 1.23 million new infections and cost $22 382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART utilization to 75% of eligible persons prevents 10.3% of infections and costs $20 300 per QALY gained. A combination strategy prevents 17.3% of infections and costs $21 580 per QALY gained.

Results of Sensitivity Analysis: With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4 count is greater than 0.350 x 109 cells/L prevents 20% to 28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%.

Limitation: The model of disease progression and treatment was simplified, and acute HIV screening was excluded.

Conclusion: Expanding HIV screening and treatment simultaneously offers the greatest health benefit and is cost-effective. However, even substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U.S. HIV epidemic without substantial reductions in risk behavior.

Primary Funding Source: National Institute on Drug Abuse, National Institutes of Health, and Department of Veterans Affairs.

Approximately 56 000 persons in the United States acquire HIV annually. This number has not decreased in recent years and highlights the need for expanded HIV screening and treatment (1, 2). Routine HIV screening facilitates early identification of HIV infection, linking infected persons with access to life-saving treatments. If accompanied by an effective counseling program, HIV screening may reduce sexual activity and other risky behavior among participants (3-7). Once identified, persons infected with HIV who are eligible to receive antiretroviral therapy (ART) can benefit from substantially reduced mortality and improved quality of life. Moreover, suppressive ART may reduce overall HIV transmission in the population by reducing a recipient's blood plasma viral load and subsequent infectivity (8-14).

Discussion

We aimed to assess the population-wide effects of expanded HIV treatment and screening on the HIV epidemic in the United States. Although previous studies have addressed the effectiveness and cost-effectiveness of either expanded HIV screening (21, 22, 24, 26) or treatment (92-94), they were not designed to fully evaluate how such programs would influence HIV transmission in the overall population or the course of the epidemic. To our knowledge, our study is the first to evaluate the population-wide effects (new HIV infections and other health outcomes) and the cost-effectiveness of alternative combinations of HIV screening and treatment in the United States.

Our study has several key findings. First, we found that expanding HIV screening and treatment could prevent 200 000 to 300 000 infections over 20 years or approximately 17% to 24% of new infections, adding up to 6.8 million QALYs to the population. To prevent 24% of new infections, routine HIV screening would need to occur annually, with antiretroviral treatment available for essentially all symptomatic patients. Our analysis assumes that persons identified as HIV-infected reduce risk behaviors by 20%; even with modest reductions in risk behavior, expansion of screening and treatment would provide enormous health benefits. If persons with HIV reduce risk behavior further, as some studies suggest (7), the health benefit could be substantially higher than we have estimated. Annual HIV screening and counseling leading to 50% behavior reduction in infected persons, along with 90% ART initiation in symptomatic patients, reduces new infections to fewer than 35 000 per year. Even under such optimistic assumptions, the U.S. HIV epidemic is unlikely to be completely eliminated without additional preventive measures.

Second, our analysis highlights the importance of emphasizing risk behavior reduction as HIV screening and treatment becomes increasingly available. For example, in addition to expanded screening and treatment, a 50% reduction in sexual risk behaviors among MSM and needle sharing among injection drug users could prevent 65% of new infections, reducing HIV incidence to approximately 20 000 cases per year. This suggests that programs to reduce risk behavior among high-risk persons will probably be a key component of a successful prevention program. If, however, uninfected persons increase risk behavior after screening, some of the benefits would be attenuated.

Our third finding is that the net benefit of implementing both interventions is greater than the sum from implementing each program individually. A substantial increase in HIV screening or treatment could prevent 95 000 or 198 000 new infections, respectively, whereas a combination program could avert 300 000 infections (an increase of 7000 infections prevented or 2%). Programs to expand screening and treatment will be most effective if they are implemented together, because each program complements the other. Essential to achieving these levels of infections averted is patient receipt of test results after diagnosis, as well as linkage to care, which has been shown to improve with nurse-initiated counseling (95) and health worker follow-up interviews with patients with new diagnoses (96).

The effectiveness of screening and counseling in reducing sexual activity will probably vary among health care settings because of the differences in risk behavior and the length, content, and intensity of counseling services. Even with no reduction in risk behavior, 1-time screening of low-risk groups and annual screening of high-risk groups could prevent nearly 4% of new infections by identifying infected persons and linking them to treatment programs. Augmenting this strategy with expanded ART prevents 16% of new infections. This suggests that preventing future infections through increased ART becomes increasingly important as the effectiveness of screening and counseling diminishes. In settings in which counseling is unavailable or ineffectual, increased utilization of ART can help ensure that expanded screening will lead to reductions in HIV transmission.

Finally, we find that expanded utilization of ART (to 75% or 90% initiating ART at a CD4 cell count less than 0.350 x 109 cells/L) is very cost-effective, as is 1-time screening of low-risk groups and annual screening of high-risk groups. Combination strategies prevent more HIV infections and increase QALYs more than either individual strategy. As noted, our analysis specifically accounts for the effect of combination screening and treatment on population-wide HIV transmission, which is a strength of our modeling framework. As routine HIV screening for adults increases across health care settings due to recently revised CDC guidelines (3), it is important to ensure that ART utilization increases at a concomitant rate. Further expanding HIV screening and counseling services, without expanding the proportion of infected persons receiving ART, does not realize the potential benefits of implementing these 2 complementary interventions.

Compared with other disease screening programs in the United States, 1-time HIV screening of low-risk persons and annual screening of high-risk persons is economically attractive, with a cost-effectiveness ratio less than $23 000 per QALY gained. This compares favorably with other accepted interventions, including screening for type 2 diabetes (97) and breast cancer mammography (98).

Our study has several limitations. First, we assumed proportional mixing among sexual partners and needle-sharing contacts, which simplifies the complex network structure of partnership formation and dissolution. Second, although we stratified the population according to sex and risk behavior, we did not include variations by race or ethnicity. To fully account for such granularity, we would need to accurately estimate sexual and needle-sharing behavior within and between races, which would be difficult to do. Moreover, significant disparities in treatment rates, background mortality, and comorbid conditions exist, and our model cannot account for these additional factors. A third limitation of our study is the omission of acute HIV screening, which would require a different model structure and specific assumptions about the benefits and costs associated with identification and treatment of acute HIV infection. The degree to which acute infection contributes to transmission is uncertain, and estimates vary (47, 99-103). Fourth, we used a simplified HIV treatment model that does not include the intricacies of individual HIV disease management; drug toxicities; CD4 cell count monitoring; or the presence of comorbid conditions, such as coronary heart disease, diabetes, and various types of cancer. Our results, however, are broadly consistent with those from more complicated models of HIV disease progression (21-24, 92, 104). Finally, we did not explicitly model development of resistance to ART, although we believe our assumptions about the benefits of ART are conservative given the introduction of new classes of ART, such as integrase inhibitors and entry inhibitors, and we evaluated scenarios that included resistance in sensitivity analyses.

Expanded HIV screening and counseling in the United States can prevent a substantial number of new HIV infections, adding millions of QALYs to the population. Programs that simultaneously expand ART utilization can prevent more HIV infections than expanding either intervention alone. Our analysis indicates that over the next 2 decades, HIV incidence in the United States could be reduced by 24% with a comprehensive expansion of screening and treatment. If these programs are accompanied by additional interventions that halve risky sexual and needle-sharing behavior, the epidemic could be reduced by 65%, suggesting the need for a comprehensive portfolio of HIV prevention, screening, and treatment.

Source
By Thomas Goldsmith
thomas.goldsmith@newsobserver.com
Posted: Sunday, Dec. 26, 2010

RALEIGH This year's deadly outbreak of Hepatitis B in an N.C. assisted-living home unfolded like a singular nightmare, but state and national experts predict such events will only grow more common in years to come.

State public health officials say poorly trained staff - who weren't required to have high school diplomas - and unsafe diabetes care led to six fatal cases of the disease at Glen Care Mount Olive, a Wayne County assisted-living center, between June and late November. By the time the presence of Hepatitis B brought state investigators to the facility in October, the transmission of infection via re-use of glucometers and other devices had probably been going on for more than four months, their report said.

"What we saw were people who were not trained in fighting infection," said Julie Henry, spokeswoman for the state Division of Public Health. "It's not even sloppiness; it's really ignorance."

Glenn Kornegay, the facility's administrator, has denied the state's conclusions and says the infections could have originated elsewhere.

A Dec. 14 reinspection by state inspectors found no additional violations, but the facility faces fines of $20,000 or more for a Type A, or highest- level, violation found during a first round of investigation in October, said officials of the state Division of Health Service Regulation. Efforts to reach Kornegay this week were unsuccessful.

The deaths at Glen Care have fueled concerns about the training and supervision required of assisted-living staffers, the subject of a long-running debate in North Carolina.

Under state and federal law, only highly trained professionals such as registered and licensed practical nurses can administer insulin at nursing homes, designed for residents with higher levels of medical needs.

But the state-overseen assisted-living centers, once known as rest homes, have much looser guidelines. At these facilities, "med techs," who are unlicensed and may get only one-on-one training from a nurse on diabetes care, are allowed to take blood glucose samples and inject insulin for people with diabetes.

"We see this over and over again, where a staff member is providing care to multiple residents," said Nicola Thompson, an epidemiologist at the federal Centers for Disease Control in Atlanta. "We know that the majority of staff in assisted living are paraprofessionals that don't have a degree in health care.

"With more people with diabetes and more people in long-term care, the situation is unlikely to get any better."

State and national public health experts say they have tried for years to change this seeming contradiction in standards.

"There is a disconnect there," said Polly Johnson, former executive director of the state Board of Nursing and now CEO of the nonprofit Foundation for Nursing Excellence.

"Part of that disconnect is related to the way assisted living was set up - not as a health-focused system."

Assisted-living centers are an industry that grew out of county rest homes. They are cheaper than nursing homes, in part, because health care is supposedly incidental to simply helping residents with activities such as bathing and eating.

"The reality is that there are more people in assisted living with major health care needs," Johnson said.

Thompson said 29 million people, most older than 65, will have diabetes by 2050. In North Carolina today, about 1in 5 people older than 65 has diabetes.

The average age of the victims in the Glen Care outbreak of Hepatitis B was about 70. Their caregivers had not taken a state-approved infection control course, and there was no staff member named to coordinate infection control, investigators from the state Division of Public Health said.

Violations often found

Outbreaks of Hepatitis B have been identified as a public health problem for at least 20 years, Thompson said. With the first examples seen in hospitals, a notable shift followed in which the outbreaks occurred in nursing homes, and beginning in 2004, more often in assisted-living centers.

In North Carolina, state investigators often find violations of safe practice involving diabetes care; between November 2006 and this year, the state Division of Health Service Regulation fined 42 adult care homes a total of more than $238,000 for infractions involving insulin.

"Diabetes is an epidemic in this country," said Bob Konrad a member of the policy committee at the advocacy group Friends of Residents in Long Term Care.

"This is probably going to happen again and again and again as we have all these challenges in assisted living."

Dr. John Buse, a UNC Chapel Hill physician and former president of the American Diabetes Association, points out that many people with diabetes test their own blood sugar and administer insulin daily.

However, Buse also noted that insulin is a powerful drug that has to be administered with care.

"It is the drug that is most commonly associated with serious medical errors in medical facilities," Buse said. "Hopefully the people that own these facilities, that run these facilities, understand that insulin is a drug where the margin for error is very small."

Source

Is chronic hepatitis B being undertreated in the United States?

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Jnl of Viral Hepatitis
Article first published online: 8 DEC 2010

C. Cohen1, S. D. Holmberg2, B. J. McMahon3, J. M. Block1, C. L. Brosgart4, R. G. Gish5, W. T. London1,6, T. M. Block1 1Hepatitis B Foundation, Doylestown, PA; 2Centers for Disease Control and Prevention, Epidemiology and Surveillance Branch, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Atlanta, GA; 3Alaska Native Medical Center, Liver Disease and Hepatitis, Anchorage, AK; 4Children's Hospital and Research Center, Oakland; 5California Pacific Medical Center, Liver Transplant Program, San Francisco, CA; and 6Fox Chase Cancer Center, Philadelphia, PA, USA

Summary

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of end-stage liver disease, including cirrhosis, liver failure and primary liver cancer. There are now seven antiviral agents approved by the United States Food and Drug Administration (FDA) for the management of chronic HBV infection. Despite the fact that there are between 1.4 and 2 million chronic HBV infections in the United States, fewer than 50 000 people per year receive prescriptions for HBV antiviral medications. This report discusses possible explanations for the disparity between the number of people who are chronically infected and the number of people who receive treatment. Explanations for this incongruence include the potentially large number of infected persons who are unscreened and thus remain undiagnosed, and lack of access, including insurance, education and referral to appropriate medical care, particularly for disproportionately infected populations.

CONCLUSION:

In summary, the data indicate that probably 4-5% of chronic HBV patients are screened, get into care, receive treatment and then are 'successfully' treated or remain in treatment (Fig. 1). Even using the most conservative estimates, it appears that there are more than 300 000, and possibly 500 000, people in the United States with chronic HBV infections who may fall within the treatment guidelines. With only 50 000 people treated, however, the largest barriers to care are most likely at the level of patient awareness, diagnosis and access to care. These appear to be the 'slow' steps in the process; once a patient is diagnosed and able to access caregivers, they appear to have a fairly good chance of receiving appropriate treatment. The gaps between diagnosis and treatment can be explained by a number of existing barriers, including lack of patient awareness of their risk factors (e.g. belong to a high-risk ethnic group), lack of provider knowledge of which groups to screen and treat, lack of insurance or under-insured and high costs of ongoing treatment, fear of long-term medication and side-effects, reluctance to take long-term medication when a patient feels healthy and lack of knowledge among physicians about when to prescribe medication and whom to treat [28,37] (Cohen et al., unpublished data).

Although some ambiguities remain regarding the precise fraction of those infected who receive care, it seems clear that the percentage of chronic hepatitis B patients in the United States that have been diagnosed and receive antiviral therapy is in the single digits. Unfortunately, there is a lack of published data regarding screening, referral and treatment rates for chronic HBV infection in the United States. Thus, while our proposed estimates rely upon limited data and assumptions, the overwhelming body of evidence suggests that only a minority of chronic HBV-infected patients in the United States are being diagnosed and receiving appropriate treatment. As chronic HBV infection and primary liver cancer rates in the United States continue to rise, research and intervention efforts that explore and reduce barriers to care and improve rates of diagnosis, management and treatment are necessary to reduce the morbidity and mortality associated with this serious liver infection in the United States.

INTRODUCTION

Worldwide, hepatitis B is a major aetiology of primary cancer of the liver, or hepatocellular carcinoma (HCC) [1,2]. People who are chronically infected with the hepatitis B virus (HBV) carry a lifetime risk of death from end-stage liver disease or HCC of between 15% and 25% [3,4]. With more than 350 million people chronically infected worldwide, lives lost to HBV eventually could exceed 100 million.

In the United States, rates of acute HBV infection have dropped dramatically in the past decade, primarily related to universal vaccination of newborns and children [5,6]. However, high rates of chronic HBV infection still exist, particularly among high-risk adult populations [7,8]. Moreover, rates of HCC in the United States, the second deadliest cancer in terms of survival time, are one of the fastest growing cancers in incidence [9,10].

There is growing evidence that medical interventions that reduce HBV viremia by inhibiting viral replication, or that immunologically enhance the host through the action of interferons, can decrease the risk of developing HCC and end-stage liver disease and consequently improve long-term patient outcomes [11-13].

Current professional practice guidelines recommend intervention for only a subset of chronically infected individuals [13]. We note, however, that many HBV carriers whose clinical profile at the time of evaluation does not meet the current professional society guidelines for recommendation of therapy may still remain at significant lifetime risk for liver disease [14-16]. Some of these persons may later fulfil criteria for treatment. The question as to who should be treated is an ongoing question and will likely change over time as more studies identify additional risk factors and biologic markers that are associated with the subsequent development of HCC and cirrhosis. Unfortunately, we do not know at any given time, what proportion of persons in the global HBV-infected population need to be treated because of the paucity of population-based studies. Currently, treatment is limited to the sub-population of HBV carriers whose current clinical profile places them within the current guidelines, which are generally characterized as those who present with biochemical and histological features of moderate or severe liver disease. It is possible that a large number of HBV-infected people in the United States, perhaps as many as 500 000 (25% of the higher estimate), currently fall or will fall during their lifetimes within these guidelines but are not being treated.

Based upon US Food and Drug Administration (FDA)-approved prescription information provided by Gilead Sciences, the number of people currently receiving prescription treatment for HBV in the United States is approximately 50 000, as illustrated in Fig. 1 (prescription estimates: courtesy Gilead Sciences). This means that fewer than 2.5-5% of the total chronically infected population, and, overall, possibly <10% of those who meet medical eligibility for HBV treatment in the United States, actually receive medication. There are several likely reasons as to why there is such a disparity between the number of individuals who are chronically infected with HBV and the number of people who are being treated. We will consider the possible explanations in this paper.

RESULTS

Undiagnosed chronic HBV infection

The number of people that have been diagnosed with chronic HBV and are also 'aware' of their disease status is unclear. Estimates vary widely as to the percentages of those who are infected and who are aware of their disease. For example, it has been estimated that as few as 8%, and as many as 60%, of the infected population in the United States are aware of their hepatitis B status [5,17-23] (Cohen et al. unpublished data). One explanation for the uncertain and low diagnosis rates for chronic HBV infections in the United States is the natural history of the disease. Because most chronic HBV infections are not apparent, those infected may be unaware of their infection status, for example as many as 60% of those chronically infected report having no symptoms [5]. The absence of routine screening of high-risk populations also contributes to under-diagnosis of chronic HBV infections.

Self-awareness of infection status may vary greatly with risk group and even with ethnic group. Most large surveys of East Asians and others from regions of high HBV endemicity indicate that self-awareness of chronic HBV infection status prior to testing for HBV is closer to 30-40% among Asian and Pacific Islander (API) Americans [5,17-22]. Surveys in urban foreign-born API communities have indicated screening rates as low as 8% [21].

There is also little information about self-awareness of HBV status among gay men [23] and injection drug users (IDUs) [24], two other major risk groups for HBV infection. Most studies have focused on improving HBV vaccination rates rather than diagnosing infected persons. However, it appears that most HBV-infected gay men are also either unaware of their HBV status or consider themselves not at risk [23,25]. Only 2000 cases of acute HBV in IDUs are reported to the Centers for Disease Control and Prevention (CDC) each year [26], and most of these will not develop into chronic infection; this suggests that the vast majority of the estimated HBV-infected IDUs (at least 15% of the total US chronic HBV infections) are untested and unaware of their infection.

Taking these data together, a diagnosis rate of <40% and probably closer to 20-30%, rather than 60%, seems the most likely scenario in the United States. Using a compromise estimate of 30% means that of the 1.4-2 million HBV-infected individuals [5,8], an estimated 420 000-600 000 are currently aware of their infection, leaving an education, treatment and surveillance gap that could affect up to 1.4 million Americans (Fig. 1).

Diagnosed, but not in care

Of those who know their status, how many are referred to and access health care, at least initially, for HBV? It appears that many, if not most, people who are aware of their infection status do not or cannot obtain appropriate follow-up care (as defined by professional practice guidelines). Research indicates that only a minority of those diagnosed as chronically infected are able to access care [27,28]. When persons are screened in hospital or as part of a targeted screening and intervention effort, up to 66% of those found to be infected are evaluated and referred to appropriate care [29,30]. However, it is estimated that only 40% of those screened in community clinics and medical offices are referred and linked to appropriate care [29,31].

Thus, probably fewer than half of all who are diagnosed to be chronically infected with HBV are referred for appropriate care. Taking our above estimate that between 420 000 and 600 000 individuals in the United States have been diagnosed, we can estimate that approximately 200 000-300 000 have subsequently entered into care, as illustrated in Fig. 1.

Diagnosed and in care, but not receiving treatment

End-stage liver disease or HCC because of HBV does not occur in everyone with chronic HBV infection [3,4]. In most, but by no means all, chronically infected individuals, cirrhosis and HCC, when it occurs, do not appear until decades after initial infection [5]. Thus, people chronically infected with HBV are heterogeneous with respect to clinical status. Leading professional societies have suggested that only subsets of the infected population be treated, based upon disease activity, risk of disease progression and likelihood of intervention effectiveness.

For example, the American Association for the Study of Liver Disease (AASLD) practice guidelines are largely limited to those with elevated HBV DNA (viral load), elevated serum alanine aminotransferase (ALT) levels and evidence of moderate to severe inflammation or fibrosis on liver biopsy or surrogate testing, as well as those with the presence of decompensated cirrhosis [13]. Persons with a family history of HCC who have any active liver disease or an elevated HBV DNA level, and are over 40 years of age, are considered for treatment [13]. Persons co-infected with human immune-deficiency virus (HIV) should receive two antiviral drugs that cover HBV as part of their HIV treatment cocktail [13]. Finally, persons co-infected with the hepatitis C virus (HCV) who meet the same criteria for HBV treatment should be treated for both infections [13]. In addition, the prevalence of hepatitis delta virus (HDV) infection is poorly described in the United States; the HBV-HDV co-infection is associated with a high risk of developing cirrhosis and an increased rate of HCC, according to most studies [4,8,13]. Importantly, the primary treatment is interferon.

There is limited information about the proportion of chronic HBV-infected individuals who actually fall within the criteria for treatment. Community-based studies vary in their estimates of the percentages of those chronically infected who are hepatitis B e-antigen (HBeAg) positive, HBV DNA positive and have greater than normal ALT levels. The estimates of those with HBV who would fall within the professional treatment guidelines range from 25% to 50%, depending on the populations studied [15,16,32,33]. However, in many community settings, it is clear that fewer than 25% of those found to be chronically infected who are in the health care system receive any of the therapeutic drugs now approved for HBV [31,34]. This low treatment rate is supported by recent data from the CDC-sponsored Chronic Hepatitis Cohort Study (CHeCS) in which data from a cross-sectional analysis showed that only 15% (or 63 of 423) HMO-sponsored patients in 2008 received antiviral drugs for HBV (S. Holmberg, unpublished data).

Thus, as illustrated in Fig. 1, the total number of treatment-eligible individuals in the United States could be between 350 000 and 500 000, which represents 25% of the low (1.4 million) and high (2 million) US prevalence estimates. With only 50 000 current prescriptions for HBV in the United States, we have a situation where only 10-15% of potentially eligible individuals are receiving treatment. However, taking our above estimate that between 200 000 and 300 000 infected individuals enter into care, 50 000 written prescriptions indicate that once a person with HBV enters care in the United States, there is a fairly high likelihood that they will receive treatment as per the guidelines. Thus, the most important limiting step appears to be screening and identifying chronically infected individuals; the biggest barrier to treatment is proper identification of those at risk.

Diagnosed and previously treated

Another possible explanation for the current low level of HBV treatment is that a large number of the 1.4-2 million chronically infected individuals might have already been treated, resulting in either benefit or lack of efficacy. However, this is unlikely because preliminary findings from a study conducted by the Hepatitis B Foundation suggest that no more than 80 000 people in the United States have been treated with FDA-approved medications over the past 10 years (T. Block et al., work in progress). Thus, prior treatment can account for only a small proportion of the current putative undertreatment, or treatment disparity, as only a very small percentage of people in the United States have received treatment in the past for chronic HBV infection.

DISCUSSION

There is a clear disparity between the number of people in the United States who have chronic hepatitis B infection and the number who receive treatment. This disparity remains largely unexplored, and the ideas expressed in this report, while speculative and based on limited information, point to the need for universal screening of populations at high risk for HBV infection, identified by CDC guidelines, as well as further research and interventions targeted at developing effective methods of ensuring that chronically infected individuals receive regular monitoring of their infection and be treated if and when appropriate.

As stated in the recent US National Academies of Sciences Institute of Medicine (IOM) report on Hepatitis and Liver Cancer [35], chronic HBV infection remains an under-diagnosed disease in the United States. To improve diagnosis rates in high-risk groups, the CDC issued expanded HBV screening guidelines in September 2008 [5]. However, it is not known how well these guidelines have been translated into practice by physicians. There are also a number of personal and environmental barriers that contribute to low screening rates, especially in foreign-born and first generation API populations. Personal barriers can include lack of information or misinformation about the disease; cultural beliefs regarding physician usage when not feeling ill; and fear of stigmatization and discrimination by family, friends and community members [19,28,36]. HBV knowledge deficits have been reported in API communities, regarding transmission, prevention, diagnosis and treatment outcomes of HBV [20,21,28,37]. Personal factors are a primary contributory barrier to screening and diagnosis, which can be overcome: studies have shown that people in at-risk populations who have more accurate knowledge about HBV are the most likely to be screened for their HBV status [20,21].

Environmental barriers to HBV diagnosis, particularly in high-risk ethnic immigrant populations, include lack of access to routine, ongoing medical care because of lack of insurance or being under-insured and difficulty navigating the US health care system [27,29,35]. Data indicate that some groups of foreign-born APIs have high rates of noninsurance, resulting in postponement of seeking care and difficulty obtaining care [38,39]. APIs also report lower use of most health care services including cancer screenings and are less likely to have a source of ongoing health care, representing barriers that are exacerbated by limited English proficiency [39,40]. With up to 70% of chronic HBV infections occurring in foreign-born individuals [5], one can estimate that up to 500 000 chronically infected individuals in the United States have no health insurance (e.g. 400 000 foreign-born and 100 000 US-born), which can be a reason for lack of diagnosis, as well as lack of treatment. Equally important are provider-related barriers: providers are often unaware of the risk groups that should be screened for HBV, or there is a communication breakdown with high-risk individuals that stems from language and cultural barriers, especially with foreign-born persons from endemic regions [37,41-43].

Personal and environmental barriers can help to explain why over 1 million chronically HBV-infected individuals in the United States remain undiagnosed, and why many of those who have been diagnosed still do not receive care and treatment. Research to reduce barriers and improve access to diagnosis and care for infected individuals in the United States is necessary if the gaps are to be overcome. Public education and awareness campaigns need to play an important role in promoting HBV screening and vaccination to high-risk communities. There are a number of culturally and linguistically appropriate programs that have had some success in improving HBV-related knowledge, as well as screening rates [27,44-46]. With more recent public attention paid to viral hepatitis, as well as the 2010 IOM report [35], it is hoped that additional funding will be made available to support a national, comprehensive educational campaign that will reduce HBV-associated stigma and significantly improve rates of screening and linkage to care. It is also important to note that continued efforts to educate providers must coincide with any public awareness campaign to help overcome provider-related barriers to HBV screening, including lack of knowledge [41,47,48].

While those with inactive disease still are at risk for HCC, albeit at a much lower rate, better methods and markers not only identifying those who are at risk for developing HCC or reactivating back to the immune active phase and markers for diagnosing HCC early are needed. There is a need for future research to focus on the development of new classifications of medicines to be used alone or in combination with the nucleoside analogues that will offer more potent suppression of HBV DNA and decrease the risk of resistance.

While advocating for increased screening and linkage to care, we must think about the ability of the health care system to effectively manage up to 1.4 million newly diagnosed chronically infected individuals. While increasing HBV screening rates and providing long-term medical management for those found to be infected might appear to be burdensome to the health care system, research and experience show that early identification and appropriate disease management of HBV are cost-effective when compared to the financial and quality of life costs of treating end-stage liver disease [49-56]. This has been shown many times over for both screening and management of other chronic illnesses, such as diabetes, hypertension and HIV infection [57-59]. Screening and medical management of chronic HBV infection affords significant health benefits to infected individuals and can be accomplished in a cost-effective manner. In 2007, Hutton et al. [49] showed that active screening and linkage to care efforts for API populations had an incremental cost-effectiveness ratio of $36 088 per QALY gained compared with voluntary screening practices. In 2008, Spackman and Veenstra [50] showed that treatment with currently approved therapies resulted in clinical benefit for HBeAg+ patients and was cost-effective compared with no treatment. Their findings were consistent with previous studies, as well [51,53,55]. Most recently, Armbruster and Brandeau [56] developed a model leveraging disease prevalence with screening and contact tracing rates to optimize cost-effective strategies for controlling HBV. This model can be used as a template for future large-scale HBV screening and linkage to care efforts in the United States.

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Seafood safety concerns for those with liver disease

Posted: 12/29/2010 10:44:26 PM PST

Last week (hallelujah!), there was progress in Washington, D.C. After a Senate vote in November edged us one step closer to better food safety in the U.S., the House of Representatives also approved the bill. The reform is long overdue.

Remember, if you will, recent nationwide outbreaks from eggs, peanuts, and spinach. These cataclysms killed more than a dozen people and sickened thousands more.

In the future, new laws enabling the FDA to recall tainted food should help contain outbreaks; more money for inspection here and abroad will nip others in the bud.

Nonetheless, reducing food-borne illness to the lowest possible levels also requires consumer education and collaboration. Above all, consumers with underlying disease need to go the extra mile to protect themselves. Why? Statistically and biologically, they are the ones with the worst outcomes from food-borne blights.

A poignant case from the 1990s illustrates my point.

The patient was a 41-year-old Central American with long-standing liver disease due to hepatitis C. The good news? She was well-insured, had excellent physicians, and followed medical advice to a T. The bad news? She did not realize her risk of illness from eating raw or undercooked seafood.

And so, on a warm afternoon in early fall, a relative went to a local fish store and purchased oysters. Within an hour or two, the entire family shared in the feast.

One day later - although no one else was sick - the patient started running a fever. Then her eyes turned yellow and her blood pressure plunged.

But it was her skin that ultimately showed telltale signs of a unique and deadly invader. By the time the patient reached the hospital in shock, large hemorrhagic blisters covered both of her legs. This distinctive finding - along with cultures of blood and skin fluid - clinched her diagnosis. She had a widespread infection due to vibrio vulnificus, a marine bacteria.

So the oysters she ate were spoiled, you may be thinking about now. Well, yes - and no. Since they often live in oyster beds and do not come from human or animal waste, vibrios aren't contaminants of the usual sort; moreover, they do not cause altered appearance, taste or smell of affected seafood.

To a marine microbiologist, they are closer to normal seawater "flora" that thrive in warm-ish temperatures, thus accounting for the time-honored adage: "Only eat oysters harvested in months containing an "R." (Translated: "Brrr" months.)

Agents within the vibrio tribe that cause human disease include cholera - a toxin-bearing pathogen currently plaguing Haiti. Of the non-cholera species, V. vulnificus is the worst. Even in healthy people, quick dips in ocean water containing V. vulnificus can lead to dangerous skin infections if the bacteria breach minor cuts and scrapes.

In people with damaged livers, V. vulnificus is even scarier. Within 36 hours of ingestion, it not only invades their bloodstream, it often spreads like wildfire to their skin, producing deep, necrotic ulcers resembling third-degree burns. In this scenario, despite excellent care and antibiotics, fatality rates often top 50 percent.

Now for a special twist. During the same two-year period in which the patient described above suffered (and thankfully survived) V. vulnificus infection, 10 of 11 cases reported in Los Angeles County occurred in Spanish-speaking residents with chronic liver disease. As a result, even though California was already the first state (as of 1991) to require English and Spanish-language signs regarding the potential health risk of eating oysters from subtropical waters, the campaign was stepped up.

Today, if you walk into a seafood restaurant or store and do NOT see a sign that opens by stating, in English and Spanish: "Eating raw oysters may cause severe illness and even death in persons who have liver disease (for example, alcoholic cirrhosis), cancer or other chronic illnesses that weaken the immune system. ... " you should not hesitate to mention the lapse to a manager.

Of course, another hazard of shellfish and mollusks (in other words, oysters, clams and mussels) is hepatitis A, the most serious viral infection associated with seafood consumption. Contamination is most likely when human sewage pollutes an aquaculture site. The largest outbreak to date (affecting almost 300,000 people) occurred in China in 1988. The victims all ate clams from a sewage-sullied growing area.

Since hepatitis A virus targets the liver, it is a special threat to people with pre-existing liver disease. Fortunately, they can be well-protected by a safe and effective vaccine.

Dr. Claire Panosian Dunavan is an infectious disease specialist and a professor of medicine at the David Geffen School of Medicine at UCLA and a resident of Pasadena. She can be reached at drclaire@earthlink.net.

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What's Next for Achillion Pharma?

by: Jason Chew December 30, 2010

Achillion stock (ACHN) has been flat all year, underperforming the biotech indices as well as its peers in the Hepatitis C drug development community. The stock began to leap a couple days after the company announced that data from ongoing clinical studies of ACH-1625 has been accepted for presentation at the 21st Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL 2011) to be held February 17-21, 2011. It has since climbed from $2.73 to close at $4.00 Wednesday, a 47% increase since the December 6th announcement.

So why all the excitement? Achillion had been making headlines all year; it promoted two new drugs into the clinic, began Phase II trials for lead candidate ACH-1625, presented at multiple industry conferences, and raised a total of $71.4 million in stock offerings.

The reason, I believe, is a key phrasing in the press release, “data from ongoing clinical studies of ACH-1625” was to be presented at the conference. There is only one ongoing study: A 144 patient Phase IIa randomized, double blinded trial of ACH-1625 in combination with ribavirin and peg-interferon alpha. The trial begins with a dose-ranging 28 day phase that will be evaluated to determine the optimal dose for the final 12 week treatment phase.

The company had initially targeted March 2011 for release of the first set of results. Having the ability to move the release date up to February speaks well for trial enrollment. This data will provide the first look at how Achillion’s lead candidate performs in a larger setting and importantly, in combination with current standard of care. ACH-1625 has already been shown to significantly reduce viral loads in patients by 3 to 4.25 log10 and maintain a sustained viral response even after therapy has stopped. It has also been shown to be safe up to 2000mg/day, a level far above the highest dose tested in this Phase IIa.

Pre-clinical studies show ACH-1625 to be additive-synergistic to ribavirin and peg-interferon alpha; this study will be a first look at how well those studies translate in the clinic. Although 28 days is still short, the multiple active drug doses as well as a placebo control will allow investigators to gauge in detail the effectiveness of ACH-1625 in this combination. In any case, a full profile of the compound and its potential as part of this three-drug regimen will be in known by the end of 2011. There’s a lot riding on this study.

Aside from its lead compound, Achillion also has a lineup of several other HCV antivirals in development. The once promising ACH-1095, an inhibitor of the NS4A protease is in Phase I. It was originally developed in collaboration with Gilead (GILD), but its rights have since been handed back to the company- though Gilead still retains the ability to opt in at a later stage in the compound’s development.

Early this year in January, a second NS3 protease inhibitor, ACH-2684, was nominated to enter clinical development. It's interesting that Achillion is developing additional NS3 inhibitors considering there are so many out there. This one is being positioned as more potent and effective against commonly seen viral mutants. It will enter Phase I trials in 2011.

The NS5A inhibitor, ACH-2928, was nominated in mid-year. It is also set to initiate Phase I testing in 2011. ACH-2928 is one of the few NS5A inhibitors currently in development. The most prominent competitor compound is BMS-790052 from Bristol Myers Squibb (BMY), currently in Phase II and looking pretty good. Both of these compounds have similarly high potencies in vitro.

Achillion also has some work in antibiotics and HBV, but they are not a major focus. The goal now is to push forward with its HCV pipeline. 2011 will be pivotal for the company as data comes in from its lead project. Funds raised during the year will allow it to complete both portions of the Phase II trial and at the same time initiate two separate Phase I studies. It will be interesting to see how the company chooses to proceed from there.

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New year, new science

Published online 31 December 2010
Nature doi:10.1038/469012a

Nature looks at key findings and events that could emerge from the research world in 2011.

Richard Van Noorden , Heidi Ledford & Adam Mann

The Eemian revealed The North Greenland Eemian Ice Drilling (NEEM) project reached bedrock in July 2010, at a depth of more than 2,500 metres. The fruits of that effort should soon be seen, now that researchers are analysing gas and particles trapped inside the ice core to reveal details of the climate of the Eemian interglacial period (130,000–115,000 years ago), when the average global temperature was about 5°C warmer than today.

GWAS prove their worth Genome-wide association studies (GWAS) have uncovered plenty of links between diseases and particular regions of the genome, but frustratingly haven't revealed much about the biochemistry behind these associations. In 2011, expect to see real mechanistic insights explaining how genes, and non-coding regions, affect the medical conditions they have been linked with. Metabolism, obesity and diabetes are among the hottest targets.

Stem cells: ready for study Researchers have learned how to reprogram people's cells into induced pluripotent stem (iPS) cells, and on from that into other cell types: skin cells can be turned into nerve cells, for example. Patient-derived iPS cells will increasingly be used as models for studying medical conditions — particularly those, such as psychiatric disorders, for which there are no good animal models, and little understanding of what is happening inside cells. They will also be used to screen potential drugs, and to probe why existing drugs help some patients but not others.

Genome-sequencing explosion This year should surely see the price of human-genome sequencing dropping to US$1,000 per genome. As next-generation sequencing machines reach the market, the number of fully sequenced human genomes will skyrocket.

That damned elusive Higgs Although it is unlikely that the Higgs boson will be spotted this year by the Large Hadron Collider near Geneva, Switzerland, there's a good chance the collider will turn up something, such as evidence for supersymmetry — the theory that every known fundamental particle has an undiscovered, superheavy partner. Meanwhile, Fermilab's Tevatron in Batavia, Illinois, is pushing for an extension beyond its September 2011 shutdown, and still hopes to hit the Higgs jackpot.

Dark matter's moment of truth A number of underground experiments, such as XENON100 at Italy's Gran Sasso National Laboratory near L'Aquila, and the Cryogenic Dark Matter Search (CDMSII) in northern Minnesota's Soudan Mine, are hunting for dark matter particles and expect to release results in 2011.

Hepatitis C treatment Eagerly anticipated drug approvals in 2011 include a decision by the US Food and Drug Administration on telaprevir, which could provide relief for the 3% of the world's population infected with the hepatitis C virus. The drug was developed by Vertex Pharmaceuticals in Cambridge, Massachusetts.

Another Earth Planet-hunters anticipate that NASA's Kepler telescope will reveal an Earth-like planet orbiting a Sun-like star. It has already spotted hundreds of planets outside the Solar System, although full data have not yet been released.

Synthetic biology: think multicellular No longer will scientists have to cram compli­cated synthetic biology into a single cell. Last year, researchers engineered an entire colony of bacteria to periodically fluoresce in unison, and we can expect many more papers exploring the behaviour of collections of cells. The goal is to exploit this teamwork to give bacteria useful functions such as producing medicinal drugs.

Last of the shuttles The final flight of NASA's space-shuttle fleet is scheduled for April, when it will deliver the Alpha Magnetic Spectrometer (AMS) to the International Space Station to search for antimatter and dark matter. However, the US Congress may authorize another shuttle outing in November. If the second test launch of Dragon, the craft developed by commercial spaceflight firm SpaceX in Hawthorne, California, proves successful, the launch of a private spacecraft with crew or cargo is not out of the question.

Solar-system explorers In March, NASA's Messenger mission is due to become the first craft ever to orbit Mercury, and the agency's Dawn probe will orbit one of the biggest members of the asteroid belt, Vesta, in August. Other planned space launches include Juno, which will orbit Jupiter's poles; the GRAIL mission, twin spacecraft due to measure the Moon's gravitational field; and the Mars Science Laboratory, a car-sized rover that will explore the red planet.

Superlaser flirts with fusion California's National Ignition Facility (pictured), the world's most power­ful laser, is inching its way to triggering ignition, when fusion reactions in a target of hydrogen isotopes should produce more energy than the laser delivers. Experts give even odds that the laser, at the Lawrence Livermore National Laboratory, will succeed this year.

Probing home GOCE, a NASA satellite designed to measure Earth's gravity field in unprecedented detail, will publish results next year that will be used to help monitor sea level rise. Meanwhile, the Aquarius satellite will launch to measure ocean salinity, and Glory will monitor solar irradiance and aerosols.

How good were Nature's predictions for 2010? See: go.nature.com/8e4y1m

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Contamination Prompts Recall of Liver Protectant

By John Gever, Senior Editor, MedPage Today
Published: December 30, 2010

Six lots of injectable acetylcysteine (Acetadote) manufactured by Cumberland Pharmaceuticals have been recalled because of particulate matter found in some vials, the company said.

The drug is used to prevent acute liver injury in patients taking potentially toxic amounts of acetaminophen.

Cumberland said it was not aware of any adverse events but was recalling the products as "a precautionary measure."

The company believes the particles originated in the product's glass containers, which were produced by a former supplier. Cumberland said it switched to a different source of vials in August 2009.

The exact product being recalled is Acetadote (acetylcysteine) Injection, 20% solution (200mg/mL) in 30 mL single dose glass vials, NDC 66220-107-30.

Affected lot numbers, with expiration dates, include 090304 and 090331 (February 2011), 090401 (March 2011), 090511 (April 2011), and 090602 and 090616 (May 2011).

The product was distributed to U.S. wholesalers and distributors nationwide.

Cumberland's announcement did not include specific instructions to hospitals or other providers who may have the product in stock. The company, based in Nashville, can be contacted at (877) 484-2700.

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