The Hospitalist

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

SYDNEY - Australia declared on Monday the AIDS epidemic is no longer a public health issue there, a month after the United Nations adopted an ambitious target to eliminate the threat globally by 2030.

The government-backed Australian Federation of AIDS Organisations (AFAO) and top scientists said the number of people being diagnosed with AIDS in Australia was now so small it was no longer reported.

AIDS cases in Australia peaked in 1994, at 953 cases, according to the Kirby Institute for infection and immunity in society.

Since then, following the introduction of antiretroviral treatment, that prevent AIDS developing in people who are infected with the HIV virus, and awareness campaigns, AIDS diagnoses have declined sharply.

"Australia is incredibly fortunate to be in the position and its because of farsighted government policy," said Darryl O'Donnell, chief executive AFAO.

"We had community organizations of gay men, sex workers and drug users doing outreach campaigns that were extraordinarily effective," O'Donnell said.

A spokeswoman for the Federal Department of Health said while it was tremendous that AIDS was "not the automatic death sentence that it once was," approximately 1,100 cases of HIV are detected each year.

"We must not let down our guard."

Worldwide there are 36.7 million people living with HIV, according to the World Health Organisation, with 180,000 people dying from AIDS-related illness in the Asia-Pacific region last year.

The United Nations agreed a new declaration on ending the AIDS epidemic at a meeting in New York last month.

The UNAIDS Fast-Track approach to ending the AIDS epidemic has a set of time-bound targets, including reducing the number of people newly infected with HIV from 2.1 million in 2015 to fewer than 500,000 in 2020, reducing the number of people dying from AIDS-related illnesses from 1.1 million in 2015 to fewer than 500,000 in 2020 and eliminating HIV-related discrimination.

Andrew Grulich, head of the HIV Epidemiology and Prevention Program at the Kirby Institute, said other countries could learn from Australia.

"The thing that has characterized Australia is a partnership between all sectors involved," he said. "Community, research and the government - and having bipartisan political support."

SYDNEY - Australia declared on Monday the AIDS epidemic is no longer a public health issue there, a month after the United Nations adopted an ambitious target to eliminate the threat globally by 2030.

The government-backed Australian Federation of AIDS Organisations (AFAO) and top scientists said the number of people being diagnosed with AIDS in Australia was now so small it was no longer reported.

AIDS cases in Australia peaked in 1994, at 953 cases, according to the Kirby Institute for infection and immunity in society.

Since then, following the introduction of antiretroviral treatment, that prevent AIDS developing in people who are infected with the HIV virus, and awareness campaigns, AIDS diagnoses have declined sharply.

"Australia is incredibly fortunate to be in the position and its because of farsighted government policy," said Darryl O'Donnell, chief executive AFAO.

"We had community organizations of gay men, sex workers and drug users doing outreach campaigns that were extraordinarily effective," O'Donnell said.

A spokeswoman for the Federal Department of Health said while it was tremendous that AIDS was "not the automatic death sentence that it once was," approximately 1,100 cases of HIV are detected each year.

"We must not let down our guard."

Worldwide there are 36.7 million people living with HIV, according to the World Health Organisation, with 180,000 people dying from AIDS-related illness in the Asia-Pacific region last year.

The United Nations agreed a new declaration on ending the AIDS epidemic at a meeting in New York last month.

The UNAIDS Fast-Track approach to ending the AIDS epidemic has a set of time-bound targets, including reducing the number of people newly infected with HIV from 2.1 million in 2015 to fewer than 500,000 in 2020, reducing the number of people dying from AIDS-related illnesses from 1.1 million in 2015 to fewer than 500,000 in 2020 and eliminating HIV-related discrimination.

Andrew Grulich, head of the HIV Epidemiology and Prevention Program at the Kirby Institute, said other countries could learn from Australia.

"The thing that has characterized Australia is a partnership between all sectors involved," he said. "Community, research and the government - and having bipartisan political support."

SYDNEY - Australia declared on Monday the AIDS epidemic is no longer a public health issue there, a month after the United Nations adopted an ambitious target to eliminate the threat globally by 2030.

The government-backed Australian Federation of AIDS Organisations (AFAO) and top scientists said the number of people being diagnosed with AIDS in Australia was now so small it was no longer reported.

AIDS cases in Australia peaked in 1994, at 953 cases, according to the Kirby Institute for infection and immunity in society.

Since then, following the introduction of antiretroviral treatment, that prevent AIDS developing in people who are infected with the HIV virus, and awareness campaigns, AIDS diagnoses have declined sharply.

"Australia is incredibly fortunate to be in the position and its because of farsighted government policy," said Darryl O'Donnell, chief executive AFAO.

"We had community organizations of gay men, sex workers and drug users doing outreach campaigns that were extraordinarily effective," O'Donnell said.

A spokeswoman for the Federal Department of Health said while it was tremendous that AIDS was "not the automatic death sentence that it once was," approximately 1,100 cases of HIV are detected each year.

"We must not let down our guard."

Worldwide there are 36.7 million people living with HIV, according to the World Health Organisation, with 180,000 people dying from AIDS-related illness in the Asia-Pacific region last year.

The United Nations agreed a new declaration on ending the AIDS epidemic at a meeting in New York last month.

The UNAIDS Fast-Track approach to ending the AIDS epidemic has a set of time-bound targets, including reducing the number of people newly infected with HIV from 2.1 million in 2015 to fewer than 500,000 in 2020, reducing the number of people dying from AIDS-related illnesses from 1.1 million in 2015 to fewer than 500,000 in 2020 and eliminating HIV-related discrimination.

Andrew Grulich, head of the HIV Epidemiology and Prevention Program at the Kirby Institute, said other countries could learn from Australia.

"The thing that has characterized Australia is a partnership between all sectors involved," he said. "Community, research and the government - and having bipartisan political support."

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p<0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p<0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p<0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p<0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p<0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p<0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p<0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p<0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p<0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

Theranos Inc founder and CEO Elizabeth Holmes, once touted as the Steve Jobs of biotech for her company's innovative blood-testing technology, has been barred by a U.S. regulator from owning or operating a lab for at least two years.

Dealing the biggest blow yet to the privately held company, the Centers for Medicare & Medicaid Services revoked a key certificate for its California lab and terminated the facility's approval to receive government payments.

Medicare is the government's medical insurance program for the elderly, while Medicaid is for the poor.

The sanctions, which also include an unspecified monetary penalty, come six months after the regulator sent a scathing letter to the company, saying its practices were jeopardizing patient health and safety.

Theranos said late on Thursday that it would continue to service its customers through its Arizona lab.

The company, once valued at $9 billion, was founded by Holmes in 2003 to develop an innovative blood testing device that would give quicker results using just one drop of blood.

However, its fortunes waned after the Wall Street Journal published a series of articles starting in October last year that suggested the devices were flawed and inaccurate.

Forbes magazine said last month that the company's value had fallen to about $800 million, while Holmes' own net worth had shrunk to zero from about $4.5 billion - a figure the magazine had said had made her the richest self-made woman in America.

"Everyone wanted her to succeed," Steve Brozak, president of WBB Securities, told Reuters, noting that the basic blood diagnostics sector has not had a significant advance in technology in 90 years.

Walgreens Boots Alliance terminated its relationship with the company last month and closed operations at all 40 Theranos Wellness Centers at its drug stores in Arizona.

Theranos is also facing a class action lawsuit filed in May accusing it of endangering customer health through "massive failures" that misrepresented test results.

The Palo Alto, California-based company is also being investigated by other federal and state agencies, including the U.S. Securities and Exchange Commission and the State Department of Health in Arizona.

Theranos Inc founder and CEO Elizabeth Holmes, once touted as the Steve Jobs of biotech for her company's innovative blood-testing technology, has been barred by a U.S. regulator from owning or operating a lab for at least two years.

Dealing the biggest blow yet to the privately held company, the Centers for Medicare & Medicaid Services revoked a key certificate for its California lab and terminated the facility's approval to receive government payments.

Medicare is the government's medical insurance program for the elderly, while Medicaid is for the poor.

The sanctions, which also include an unspecified monetary penalty, come six months after the regulator sent a scathing letter to the company, saying its practices were jeopardizing patient health and safety.

Theranos said late on Thursday that it would continue to service its customers through its Arizona lab.

The company, once valued at $9 billion, was founded by Holmes in 2003 to develop an innovative blood testing device that would give quicker results using just one drop of blood.

However, its fortunes waned after the Wall Street Journal published a series of articles starting in October last year that suggested the devices were flawed and inaccurate.

Forbes magazine said last month that the company's value had fallen to about $800 million, while Holmes' own net worth had shrunk to zero from about $4.5 billion - a figure the magazine had said had made her the richest self-made woman in America.

"Everyone wanted her to succeed," Steve Brozak, president of WBB Securities, told Reuters, noting that the basic blood diagnostics sector has not had a significant advance in technology in 90 years.

Walgreens Boots Alliance terminated its relationship with the company last month and closed operations at all 40 Theranos Wellness Centers at its drug stores in Arizona.

Theranos is also facing a class action lawsuit filed in May accusing it of endangering customer health through "massive failures" that misrepresented test results.

The Palo Alto, California-based company is also being investigated by other federal and state agencies, including the U.S. Securities and Exchange Commission and the State Department of Health in Arizona.

Theranos Inc founder and CEO Elizabeth Holmes, once touted as the Steve Jobs of biotech for her company's innovative blood-testing technology, has been barred by a U.S. regulator from owning or operating a lab for at least two years.

Dealing the biggest blow yet to the privately held company, the Centers for Medicare & Medicaid Services revoked a key certificate for its California lab and terminated the facility's approval to receive government payments.

Medicare is the government's medical insurance program for the elderly, while Medicaid is for the poor.

The sanctions, which also include an unspecified monetary penalty, come six months after the regulator sent a scathing letter to the company, saying its practices were jeopardizing patient health and safety.

Theranos said late on Thursday that it would continue to service its customers through its Arizona lab.

The company, once valued at $9 billion, was founded by Holmes in 2003 to develop an innovative blood testing device that would give quicker results using just one drop of blood.

However, its fortunes waned after the Wall Street Journal published a series of articles starting in October last year that suggested the devices were flawed and inaccurate.

Forbes magazine said last month that the company's value had fallen to about $800 million, while Holmes' own net worth had shrunk to zero from about $4.5 billion - a figure the magazine had said had made her the richest self-made woman in America.

"Everyone wanted her to succeed," Steve Brozak, president of WBB Securities, told Reuters, noting that the basic blood diagnostics sector has not had a significant advance in technology in 90 years.

Walgreens Boots Alliance terminated its relationship with the company last month and closed operations at all 40 Theranos Wellness Centers at its drug stores in Arizona.

Theranos is also facing a class action lawsuit filed in May accusing it of endangering customer health through "massive failures" that misrepresented test results.

The Palo Alto, California-based company is also being investigated by other federal and state agencies, including the U.S. Securities and Exchange Commission and the State Department of Health in Arizona.

NEW YORK - About a third of heart failure patients have anemia and most also have iron deficiency, according to UK researchers.

This observational analysis, Dr. John G.F. Cleland told Reuters Health by email, "shows that iron deficiency is very common in patients with heart failure and often leads to anemia and that the prevalence of both iron deficiency and anemia are both highly sensitive to the criteria used to define them."

In a June 29 online paper in JAMA Cardiology, Dr. Cleland, of the University of Hull, and colleagues report that they came to this conclusion after studying data on more than 4,400 patients seen at a local clinic over a 10-year period. All were referred because of suspected heart failure, and their median age was 73 years.

Data collected included hemoglobin, serum iron, transferrin saturation, and serum ferritin concentrations.

Overall, 1,237 patients (27.8%) had anemia, with a higher prevalence (33.3%) in patients who met the criteria for heart failure with or without left ventricular systolic dysfunction (LVSD).

Depending on the definition used, iron deficiency was present in 270 (43.2%) to 425 (68.0%) patients with anemia. This was the case in 260 (14.7%) to 624 (35.3%) of those without anemia.

Lower concentrations of hemoglobin (hazard ratio 0.92) and serum iron (HR 0.98) were independently associated with higher all-cause and cardiovascular mortality in multivariable analyses.

Moreover, said Dr. Cleland, "Serum iron and transferrin saturation were highly correlated (raising the question of the need to measure both) and both were strongly related to anemia. In contrast, serum ferritin, the most widely (supposed) measure of iron deficiency, was more strongly related to measures of inflammation than anemia."

"Lower concentrations of hemoglobin and serum iron and lower transferrin saturation," he stressed, "were associated with a higher mortality. In contrast, lower serum ferritin was associated with a better prognosis, probably because it is more a measure of inflammation than of iron deficiency."

Dr. Cleland concluded, "Serum ferritin is a poor measure of iron deficiency in patients with heart failure. Many patients with normal serum ferritin (defined by many as greater than 100 ng/mL) have iron deficiency. Clinical trials of intravenous iron for patients with heart failure should be aware of this issue to ensure they enroll appropriate patients."

The National Heart Service, Vifor Pharma, and Amgen supported this research. Dr. Cleland reported research support from Vifor and Amgen.

SOURCE: http://bit.ly/29ukoX4

JAMA Cardiol 2016.

NEW YORK - About a third of heart failure patients have anemia and most also have iron deficiency, according to UK researchers.

This observational analysis, Dr. John G.F. Cleland told Reuters Health by email, "shows that iron deficiency is very common in patients with heart failure and often leads to anemia and that the prevalence of both iron deficiency and anemia are both highly sensitive to the criteria used to define them."

In a June 29 online paper in JAMA Cardiology, Dr. Cleland, of the University of Hull, and colleagues report that they came to this conclusion after studying data on more than 4,400 patients seen at a local clinic over a 10-year period. All were referred because of suspected heart failure, and their median age was 73 years.

Data collected included hemoglobin, serum iron, transferrin saturation, and serum ferritin concentrations.

Overall, 1,237 patients (27.8%) had anemia, with a higher prevalence (33.3%) in patients who met the criteria for heart failure with or without left ventricular systolic dysfunction (LVSD).

Depending on the definition used, iron deficiency was present in 270 (43.2%) to 425 (68.0%) patients with anemia. This was the case in 260 (14.7%) to 624 (35.3%) of those without anemia.

Lower concentrations of hemoglobin (hazard ratio 0.92) and serum iron (HR 0.98) were independently associated with higher all-cause and cardiovascular mortality in multivariable analyses.

Moreover, said Dr. Cleland, "Serum iron and transferrin saturation were highly correlated (raising the question of the need to measure both) and both were strongly related to anemia. In contrast, serum ferritin, the most widely (supposed) measure of iron deficiency, was more strongly related to measures of inflammation than anemia."

"Lower concentrations of hemoglobin and serum iron and lower transferrin saturation," he stressed, "were associated with a higher mortality. In contrast, lower serum ferritin was associated with a better prognosis, probably because it is more a measure of inflammation than of iron deficiency."

Dr. Cleland concluded, "Serum ferritin is a poor measure of iron deficiency in patients with heart failure. Many patients with normal serum ferritin (defined by many as greater than 100 ng/mL) have iron deficiency. Clinical trials of intravenous iron for patients with heart failure should be aware of this issue to ensure they enroll appropriate patients."

The National Heart Service, Vifor Pharma, and Amgen supported this research. Dr. Cleland reported research support from Vifor and Amgen.

SOURCE: http://bit.ly/29ukoX4

JAMA Cardiol 2016.

NEW YORK - About a third of heart failure patients have anemia and most also have iron deficiency, according to UK researchers.

This observational analysis, Dr. John G.F. Cleland told Reuters Health by email, "shows that iron deficiency is very common in patients with heart failure and often leads to anemia and that the prevalence of both iron deficiency and anemia are both highly sensitive to the criteria used to define them."

In a June 29 online paper in JAMA Cardiology, Dr. Cleland, of the University of Hull, and colleagues report that they came to this conclusion after studying data on more than 4,400 patients seen at a local clinic over a 10-year period. All were referred because of suspected heart failure, and their median age was 73 years.

Data collected included hemoglobin, serum iron, transferrin saturation, and serum ferritin concentrations.

Overall, 1,237 patients (27.8%) had anemia, with a higher prevalence (33.3%) in patients who met the criteria for heart failure with or without left ventricular systolic dysfunction (LVSD).

Depending on the definition used, iron deficiency was present in 270 (43.2%) to 425 (68.0%) patients with anemia. This was the case in 260 (14.7%) to 624 (35.3%) of those without anemia.

Lower concentrations of hemoglobin (hazard ratio 0.92) and serum iron (HR 0.98) were independently associated with higher all-cause and cardiovascular mortality in multivariable analyses.

Moreover, said Dr. Cleland, "Serum iron and transferrin saturation were highly correlated (raising the question of the need to measure both) and both were strongly related to anemia. In contrast, serum ferritin, the most widely (supposed) measure of iron deficiency, was more strongly related to measures of inflammation than anemia."

"Lower concentrations of hemoglobin and serum iron and lower transferrin saturation," he stressed, "were associated with a higher mortality. In contrast, lower serum ferritin was associated with a better prognosis, probably because it is more a measure of inflammation than of iron deficiency."

Dr. Cleland concluded, "Serum ferritin is a poor measure of iron deficiency in patients with heart failure. Many patients with normal serum ferritin (defined by many as greater than 100 ng/mL) have iron deficiency. Clinical trials of intravenous iron for patients with heart failure should be aware of this issue to ensure they enroll appropriate patients."

The National Heart Service, Vifor Pharma, and Amgen supported this research. Dr. Cleland reported research support from Vifor and Amgen.

SOURCE: http://bit.ly/29ukoX4

JAMA Cardiol 2016.

NEW YORK - Long-term use of the bisphosphonate alendronate substantially lowers the risk of hip fracture without increasing the risk of atypical fractures of the subtrochanteric femur or femoral shaft, according to a Danish study.

"These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use," the authors conclude in the BMJ online June 28.

Placebo-controlled trials have shown a reduction in hip fracture risk with alendronate treatment for three years in older women with osteoporosis, but observational studies have suggested that atypical femur fractures are more common in long-term users of bisphosphonates.

To investigate further, researchers analyzed data from Danish practice registries on nearly 62,000 alendronate users. A total of 1,428 people sustained a fracture of the subtrochanteric femur or femoral shaft (ST/FS), an incidence rate of 3.4 per 1,000 person years, and 6,784 sustained a hip fracture (incidence rate 16.2 per 1,000 person years).

"Long-term adherent use of alendronate in excess of 10 dose years was associated with an adjusted 30% lower risk of hip fracture and no increase in the risk of fractures of the subtrochanteric femur or femoral shaft," the investigators report in their paper.

"In addition, we have shown that even in the worst case scenario (assuming 100% of subtrochanteric and femoral shaft fractures are atypical and secondary to bisphosphonate use and making no allowance for the higher prevalence of comorbid conditions in these patients) the number of atypical femur fractures remains too low to offset the benefits on hip fracture in patients with long-term alendronate use up to 10 years," they say.

"Safety concerns have probably limited the adherence to anti-osteoporosis therapies," Dr. Daniel Preto-Alhambra, University of Oxford, Nuffield Orthopaedics Centre in the United Kingdom, who worked on the study, told Reuters Health by email.

"Our findings support a good risk-benefit for this treatment in terms of femur fracture risk reduction, even when prescribed for 10 years and over. These data should reassure physicians and patients on the bone-related risk-benefits of alendronate therapy," he added.

The study had no commercial funding. Several authors made disclosure statements.

SOURCE: http://bit.ly/29y33NQ

BMJ 2016.

NEW YORK - Long-term use of the bisphosphonate alendronate substantially lowers the risk of hip fracture without increasing the risk of atypical fractures of the subtrochanteric femur or femoral shaft, according to a Danish study.

"These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use," the authors conclude in the BMJ online June 28.

Placebo-controlled trials have shown a reduction in hip fracture risk with alendronate treatment for three years in older women with osteoporosis, but observational studies have suggested that atypical femur fractures are more common in long-term users of bisphosphonates.

To investigate further, researchers analyzed data from Danish practice registries on nearly 62,000 alendronate users. A total of 1,428 people sustained a fracture of the subtrochanteric femur or femoral shaft (ST/FS), an incidence rate of 3.4 per 1,000 person years, and 6,784 sustained a hip fracture (incidence rate 16.2 per 1,000 person years).

"Long-term adherent use of alendronate in excess of 10 dose years was associated with an adjusted 30% lower risk of hip fracture and no increase in the risk of fractures of the subtrochanteric femur or femoral shaft," the investigators report in their paper.

"In addition, we have shown that even in the worst case scenario (assuming 100% of subtrochanteric and femoral shaft fractures are atypical and secondary to bisphosphonate use and making no allowance for the higher prevalence of comorbid conditions in these patients) the number of atypical femur fractures remains too low to offset the benefits on hip fracture in patients with long-term alendronate use up to 10 years," they say.

"Safety concerns have probably limited the adherence to anti-osteoporosis therapies," Dr. Daniel Preto-Alhambra, University of Oxford, Nuffield Orthopaedics Centre in the United Kingdom, who worked on the study, told Reuters Health by email.

"Our findings support a good risk-benefit for this treatment in terms of femur fracture risk reduction, even when prescribed for 10 years and over. These data should reassure physicians and patients on the bone-related risk-benefits of alendronate therapy," he added.

The study had no commercial funding. Several authors made disclosure statements.

SOURCE: http://bit.ly/29y33NQ

BMJ 2016.

NEW YORK - Long-term use of the bisphosphonate alendronate substantially lowers the risk of hip fracture without increasing the risk of atypical fractures of the subtrochanteric femur or femoral shaft, according to a Danish study.

"These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use," the authors conclude in the BMJ online June 28.

Placebo-controlled trials have shown a reduction in hip fracture risk with alendronate treatment for three years in older women with osteoporosis, but observational studies have suggested that atypical femur fractures are more common in long-term users of bisphosphonates.

To investigate further, researchers analyzed data from Danish practice registries on nearly 62,000 alendronate users. A total of 1,428 people sustained a fracture of the subtrochanteric femur or femoral shaft (ST/FS), an incidence rate of 3.4 per 1,000 person years, and 6,784 sustained a hip fracture (incidence rate 16.2 per 1,000 person years).

"Long-term adherent use of alendronate in excess of 10 dose years was associated with an adjusted 30% lower risk of hip fracture and no increase in the risk of fractures of the subtrochanteric femur or femoral shaft," the investigators report in their paper.

"In addition, we have shown that even in the worst case scenario (assuming 100% of subtrochanteric and femoral shaft fractures are atypical and secondary to bisphosphonate use and making no allowance for the higher prevalence of comorbid conditions in these patients) the number of atypical femur fractures remains too low to offset the benefits on hip fracture in patients with long-term alendronate use up to 10 years," they say.

"Safety concerns have probably limited the adherence to anti-osteoporosis therapies," Dr. Daniel Preto-Alhambra, University of Oxford, Nuffield Orthopaedics Centre in the United Kingdom, who worked on the study, told Reuters Health by email.

"Our findings support a good risk-benefit for this treatment in terms of femur fracture risk reduction, even when prescribed for 10 years and over. These data should reassure physicians and patients on the bone-related risk-benefits of alendronate therapy," he added.

The study had no commercial funding. Several authors made disclosure statements.

SOURCE: http://bit.ly/29y33NQ

BMJ 2016.

CHICAGO - Medicare enrollees are moving in greater numbers than ever to the program's managed care option as a way to save money. But the tradeoff is much less ability to use their preferred doctors and hospitals.

Seniors can choose between traditional fee-for-service Medicare - which is accepted by most healthcare providers - or a Medicare Advantage plan. The latter encompasses health maintenance organizations (HMOs) or preferred provider organizations (PPOs), which control costs by creating healthcare provider networks that enrollees must use.

In theory, prospective Advantage enrollees can review lists of in-network providers before opting into a plan. But a new study by the Kaiser Family Foundation (KFF) finds that provider data often is very difficult to review, can be out of date and frequently contain inaccurate information.

KFF's review also found shortcomings in the quality of providers in some Medicare Advantage provider networks. One out of every five plans did not include a regional academic medical center - institutions which usually offer the highest quality care and top specialists. And only 40 percent of Advantage provider networks included top-quality cancer centers, as indicated by membership in the National Cancer Institute's network.

NCI-designated cancer centers offer cutting-edge treatments and tend to have greater access to clinical trials. They are especially important for patients with rare and advanced cancers, or other complicating conditions, said Gretchen Jacobson, KFF's associate director of the program on Medicare policy and co-author of the study.

The upshot: Medicare Advantage may be just fine if you are healthy, but problems may crop up if your healthcare needs become more complex and you have very specific healthcare provider preferences.

This year, 31 percent of Medicare enrollees are in Advantage plans, up from 11 percent in 2010. That number is expected to hit 41 percent by 2026, according to a forecast by the Congressional Budget Office.

When you sign up for Advantage, your Part B premium goes to the insurance company providing the plan. The largest providers are UnitedHealthcare, Humana Inc and Blue Cross Blue Shield.

One often hears critics claim that healthcare providers are bailing out of traditional Medicare in large numbers - but that is not actually the case. Last year, 14 percent of Medicare enrollees who were seeking a new primary care doctor reported major problems in finding a physician who would treat them, according to survey data from the Medicare Payment Advisory Commission, an independent congressional agency. Among those seeking a new specialist, 6 percent reported major problems. In both cases, that represents 1 percent of the total Medicare population.

ADVANTAGES, PITFALLS

Advantage plans often offer extra benefits, such as health club memberships, vision care and some limited dental care. Cost-sharing is often lower, and many plans provide prescription drug coverage with no extra premium. "It can be very attractive to many seniors who are living on a fixed budget," Jacobson said.

The trade-off is limited provider networks - and the challenges prospective enrollees face in determining who they are allowed to see for healthcare, and who is off-limits. KFF reviewed 409 Advantage plans, including 307 HMOs and 102 PPOs. Researchers found provider directories often were riddled with errors, omissions and outdated information.

"There's no reason in this era of technology why this needs to be as difficult as it is," Jacobson said. "People should be able to simply tell the system who their doctors are, the illnesses they have, and get a recommendation for a plan that will work for them."

KFF also found that Advantage provider network quality differs significantly. For example, Los Angeles has three NCI-designated cancer centers. Most of the Advantage plans there do not include any of them, but one plan includes all three.

A report last year by the U.S. Government Accountability Office found that the Centers for Medicare & Medicaid Services (CMS), which runs Medicare, needs to improve its oversight of Advantage plans to assure that provider networks are robust. The report also criticized CMS for doing too little to assess the accuracy of Advantage plan provider lists.

Even when Advantage enrollees are able to confirm participation by their healthcare providers, there is no guarantee that will continue. Advantage plans are free to add or drop health providers during the course of an enrollment season.

That became an especially hot issue in 2014 when UnitedHealthcare dropped providers who covered thousands of the insurer's patients, including the prominent Yale-New Haven Hospital system.

Democrats in Congress have proposed legislation that would prohibit Advantage plans from dropping providers without cause during the middle of an enrollment year.

Under current rules, plans must provide 30 days' notice to enrollees when providers are dropped. Enrollees who lose access to a provider can make a midyear plan change only under very limited circumstances. "You can do it only if you are receiving ongoing care from a provider that is terminated," Jacobson said. "Otherwise you need to wait until the next open enrollment period."

The annual enrollment period for Advantage and Part D prescription drug plans are held from Oct. 15 to Dec. 7 each year. At that point, a beneficiary could switch to a different Advantage plan, or shift back to traditional Medicare. But a serious diagnosis in January would leave you hamstrung until the following year.

Said Jacobson: "It can be a roll of the dice."

(The opinions expressed here are those of the author, a columnist for Reuters.)

CHICAGO - Medicare enrollees are moving in greater numbers than ever to the program's managed care option as a way to save money. But the tradeoff is much less ability to use their preferred doctors and hospitals.

Seniors can choose between traditional fee-for-service Medicare - which is accepted by most healthcare providers - or a Medicare Advantage plan. The latter encompasses health maintenance organizations (HMOs) or preferred provider organizations (PPOs), which control costs by creating healthcare provider networks that enrollees must use.

In theory, prospective Advantage enrollees can review lists of in-network providers before opting into a plan. But a new study by the Kaiser Family Foundation (KFF) finds that provider data often is very difficult to review, can be out of date and frequently contain inaccurate information.

KFF's review also found shortcomings in the quality of providers in some Medicare Advantage provider networks. One out of every five plans did not include a regional academic medical center - institutions which usually offer the highest quality care and top specialists. And only 40 percent of Advantage provider networks included top-quality cancer centers, as indicated by membership in the National Cancer Institute's network.

NCI-designated cancer centers offer cutting-edge treatments and tend to have greater access to clinical trials. They are especially important for patients with rare and advanced cancers, or other complicating conditions, said Gretchen Jacobson, KFF's associate director of the program on Medicare policy and co-author of the study.

The upshot: Medicare Advantage may be just fine if you are healthy, but problems may crop up if your healthcare needs become more complex and you have very specific healthcare provider preferences.

This year, 31 percent of Medicare enrollees are in Advantage plans, up from 11 percent in 2010. That number is expected to hit 41 percent by 2026, according to a forecast by the Congressional Budget Office.

When you sign up for Advantage, your Part B premium goes to the insurance company providing the plan. The largest providers are UnitedHealthcare, Humana Inc and Blue Cross Blue Shield.

One often hears critics claim that healthcare providers are bailing out of traditional Medicare in large numbers - but that is not actually the case. Last year, 14 percent of Medicare enrollees who were seeking a new primary care doctor reported major problems in finding a physician who would treat them, according to survey data from the Medicare Payment Advisory Commission, an independent congressional agency. Among those seeking a new specialist, 6 percent reported major problems. In both cases, that represents 1 percent of the total Medicare population.

ADVANTAGES, PITFALLS

Advantage plans often offer extra benefits, such as health club memberships, vision care and some limited dental care. Cost-sharing is often lower, and many plans provide prescription drug coverage with no extra premium. "It can be very attractive to many seniors who are living on a fixed budget," Jacobson said.

The trade-off is limited provider networks - and the challenges prospective enrollees face in determining who they are allowed to see for healthcare, and who is off-limits. KFF reviewed 409 Advantage plans, including 307 HMOs and 102 PPOs. Researchers found provider directories often were riddled with errors, omissions and outdated information.

"There's no reason in this era of technology why this needs to be as difficult as it is," Jacobson said. "People should be able to simply tell the system who their doctors are, the illnesses they have, and get a recommendation for a plan that will work for them."

KFF also found that Advantage provider network quality differs significantly. For example, Los Angeles has three NCI-designated cancer centers. Most of the Advantage plans there do not include any of them, but one plan includes all three.

A report last year by the U.S. Government Accountability Office found that the Centers for Medicare & Medicaid Services (CMS), which runs Medicare, needs to improve its oversight of Advantage plans to assure that provider networks are robust. The report also criticized CMS for doing too little to assess the accuracy of Advantage plan provider lists.

Even when Advantage enrollees are able to confirm participation by their healthcare providers, there is no guarantee that will continue. Advantage plans are free to add or drop health providers during the course of an enrollment season.

That became an especially hot issue in 2014 when UnitedHealthcare dropped providers who covered thousands of the insurer's patients, including the prominent Yale-New Haven Hospital system.

Democrats in Congress have proposed legislation that would prohibit Advantage plans from dropping providers without cause during the middle of an enrollment year.

Under current rules, plans must provide 30 days' notice to enrollees when providers are dropped. Enrollees who lose access to a provider can make a midyear plan change only under very limited circumstances. "You can do it only if you are receiving ongoing care from a provider that is terminated," Jacobson said. "Otherwise you need to wait until the next open enrollment period."

The annual enrollment period for Advantage and Part D prescription drug plans are held from Oct. 15 to Dec. 7 each year. At that point, a beneficiary could switch to a different Advantage plan, or shift back to traditional Medicare. But a serious diagnosis in January would leave you hamstrung until the following year.

Said Jacobson: "It can be a roll of the dice."

(The opinions expressed here are those of the author, a columnist for Reuters.)

CHICAGO - Medicare enrollees are moving in greater numbers than ever to the program's managed care option as a way to save money. But the tradeoff is much less ability to use their preferred doctors and hospitals.

Seniors can choose between traditional fee-for-service Medicare - which is accepted by most healthcare providers - or a Medicare Advantage plan. The latter encompasses health maintenance organizations (HMOs) or preferred provider organizations (PPOs), which control costs by creating healthcare provider networks that enrollees must use.

In theory, prospective Advantage enrollees can review lists of in-network providers before opting into a plan. But a new study by the Kaiser Family Foundation (KFF) finds that provider data often is very difficult to review, can be out of date and frequently contain inaccurate information.

KFF's review also found shortcomings in the quality of providers in some Medicare Advantage provider networks. One out of every five plans did not include a regional academic medical center - institutions which usually offer the highest quality care and top specialists. And only 40 percent of Advantage provider networks included top-quality cancer centers, as indicated by membership in the National Cancer Institute's network.

NCI-designated cancer centers offer cutting-edge treatments and tend to have greater access to clinical trials. They are especially important for patients with rare and advanced cancers, or other complicating conditions, said Gretchen Jacobson, KFF's associate director of the program on Medicare policy and co-author of the study.

The upshot: Medicare Advantage may be just fine if you are healthy, but problems may crop up if your healthcare needs become more complex and you have very specific healthcare provider preferences.

This year, 31 percent of Medicare enrollees are in Advantage plans, up from 11 percent in 2010. That number is expected to hit 41 percent by 2026, according to a forecast by the Congressional Budget Office.

When you sign up for Advantage, your Part B premium goes to the insurance company providing the plan. The largest providers are UnitedHealthcare, Humana Inc and Blue Cross Blue Shield.

One often hears critics claim that healthcare providers are bailing out of traditional Medicare in large numbers - but that is not actually the case. Last year, 14 percent of Medicare enrollees who were seeking a new primary care doctor reported major problems in finding a physician who would treat them, according to survey data from the Medicare Payment Advisory Commission, an independent congressional agency. Among those seeking a new specialist, 6 percent reported major problems. In both cases, that represents 1 percent of the total Medicare population.

ADVANTAGES, PITFALLS

Advantage plans often offer extra benefits, such as health club memberships, vision care and some limited dental care. Cost-sharing is often lower, and many plans provide prescription drug coverage with no extra premium. "It can be very attractive to many seniors who are living on a fixed budget," Jacobson said.

The trade-off is limited provider networks - and the challenges prospective enrollees face in determining who they are allowed to see for healthcare, and who is off-limits. KFF reviewed 409 Advantage plans, including 307 HMOs and 102 PPOs. Researchers found provider directories often were riddled with errors, omissions and outdated information.

"There's no reason in this era of technology why this needs to be as difficult as it is," Jacobson said. "People should be able to simply tell the system who their doctors are, the illnesses they have, and get a recommendation for a plan that will work for them."

KFF also found that Advantage provider network quality differs significantly. For example, Los Angeles has three NCI-designated cancer centers. Most of the Advantage plans there do not include any of them, but one plan includes all three.

A report last year by the U.S. Government Accountability Office found that the Centers for Medicare & Medicaid Services (CMS), which runs Medicare, needs to improve its oversight of Advantage plans to assure that provider networks are robust. The report also criticized CMS for doing too little to assess the accuracy of Advantage plan provider lists.

Even when Advantage enrollees are able to confirm participation by their healthcare providers, there is no guarantee that will continue. Advantage plans are free to add or drop health providers during the course of an enrollment season.

That became an especially hot issue in 2014 when UnitedHealthcare dropped providers who covered thousands of the insurer's patients, including the prominent Yale-New Haven Hospital system.

Democrats in Congress have proposed legislation that would prohibit Advantage plans from dropping providers without cause during the middle of an enrollment year.

Under current rules, plans must provide 30 days' notice to enrollees when providers are dropped. Enrollees who lose access to a provider can make a midyear plan change only under very limited circumstances. "You can do it only if you are receiving ongoing care from a provider that is terminated," Jacobson said. "Otherwise you need to wait until the next open enrollment period."

The annual enrollment period for Advantage and Part D prescription drug plans are held from Oct. 15 to Dec. 7 each year. At that point, a beneficiary could switch to a different Advantage plan, or shift back to traditional Medicare. But a serious diagnosis in January would leave you hamstrung until the following year.

Said Jacobson: "It can be a roll of the dice."

(The opinions expressed here are those of the author, a columnist for Reuters.)

WASHINGTON - The White House announced on Wednesday measures aimed at advancing President Barack Obama's precision medicine initiative, including plans to speed the development of tests used to identify genetic mutations and guide medical treatment.

The U.S. Food and Drug Administration said it planned to issue a proposal to create performance standards to guide development of next generation sequencing (NGS) tests. These tests scan a person's DNA and identify genetic differences that could be responsible for a patient's symptoms.

The standards would be designed to assess how accurately a test identifies a genetic variant. The developer would certify that it had met those standards. Currently the FDA itself determines the test's accuracy.

"We believe that the use of standards is the best way to allow regulation to keep pace with the evolution of NGS technology," Dr. Robert Califf told reporters on a conference call.

A second FDA proposal would allow test developers to use data from publicly accessible genetic databases, not just their own data, to demonstrate that the test accurately predicts disease. Califf said the approach could potentially get rid of the need for the FDA to review the tests before they reach the market.

"Taken together, these guidances will foster innovation, assure the quality and reliability of NGS-based tests and promote their adoption into clinical practice," he said.

The FDA's action is part of a broader government initiative to promote the development of individually tailored medicines. Obama introduced the initiative in his State of the Union address last year, saying he wanted the United States to lead a new era of medicine, "one that delivers the right treatment at the right time."

As part of the project, the National Institutes of Health will invest $55 million to build the infrastructure needed to collect genetic data from more than 1 million volunteers, its director, Dr. Francis Collins, said on the conference call.

Collins said it will take three to four years to assemble the desired amount of genetic material, which will then be available to researchers to help develop drugs for cancer and other disease. Anyone, he said, can participate.

"This is about all of us," he said. "Participants will be true partners, not subjects, not patients." Data sharing, he added, will be "swift."

WASHINGTON - The White House announced on Wednesday measures aimed at advancing President Barack Obama's precision medicine initiative, including plans to speed the development of tests used to identify genetic mutations and guide medical treatment.

The U.S. Food and Drug Administration said it planned to issue a proposal to create performance standards to guide development of next generation sequencing (NGS) tests. These tests scan a person's DNA and identify genetic differences that could be responsible for a patient's symptoms.

The standards would be designed to assess how accurately a test identifies a genetic variant. The developer would certify that it had met those standards. Currently the FDA itself determines the test's accuracy.

"We believe that the use of standards is the best way to allow regulation to keep pace with the evolution of NGS technology," Dr. Robert Califf told reporters on a conference call.

A second FDA proposal would allow test developers to use data from publicly accessible genetic databases, not just their own data, to demonstrate that the test accurately predicts disease. Califf said the approach could potentially get rid of the need for the FDA to review the tests before they reach the market.

"Taken together, these guidances will foster innovation, assure the quality and reliability of NGS-based tests and promote their adoption into clinical practice," he said.

The FDA's action is part of a broader government initiative to promote the development of individually tailored medicines. Obama introduced the initiative in his State of the Union address last year, saying he wanted the United States to lead a new era of medicine, "one that delivers the right treatment at the right time."

As part of the project, the National Institutes of Health will invest $55 million to build the infrastructure needed to collect genetic data from more than 1 million volunteers, its director, Dr. Francis Collins, said on the conference call.

Collins said it will take three to four years to assemble the desired amount of genetic material, which will then be available to researchers to help develop drugs for cancer and other disease. Anyone, he said, can participate.

"This is about all of us," he said. "Participants will be true partners, not subjects, not patients." Data sharing, he added, will be "swift."

WASHINGTON - The White House announced on Wednesday measures aimed at advancing President Barack Obama's precision medicine initiative, including plans to speed the development of tests used to identify genetic mutations and guide medical treatment.

The U.S. Food and Drug Administration said it planned to issue a proposal to create performance standards to guide development of next generation sequencing (NGS) tests. These tests scan a person's DNA and identify genetic differences that could be responsible for a patient's symptoms.

The standards would be designed to assess how accurately a test identifies a genetic variant. The developer would certify that it had met those standards. Currently the FDA itself determines the test's accuracy.

"We believe that the use of standards is the best way to allow regulation to keep pace with the evolution of NGS technology," Dr. Robert Califf told reporters on a conference call.

A second FDA proposal would allow test developers to use data from publicly accessible genetic databases, not just their own data, to demonstrate that the test accurately predicts disease. Califf said the approach could potentially get rid of the need for the FDA to review the tests before they reach the market.

"Taken together, these guidances will foster innovation, assure the quality and reliability of NGS-based tests and promote their adoption into clinical practice," he said.

The FDA's action is part of a broader government initiative to promote the development of individually tailored medicines. Obama introduced the initiative in his State of the Union address last year, saying he wanted the United States to lead a new era of medicine, "one that delivers the right treatment at the right time."

As part of the project, the National Institutes of Health will invest $55 million to build the infrastructure needed to collect genetic data from more than 1 million volunteers, its director, Dr. Francis Collins, said on the conference call.

Collins said it will take three to four years to assemble the desired amount of genetic material, which will then be available to researchers to help develop drugs for cancer and other disease. Anyone, he said, can participate.

"This is about all of us," he said. "Participants will be true partners, not subjects, not patients." Data sharing, he added, will be "swift."

Physicians wrote significantly fewer prescriptions for painkillers and other medications for elderly and disabled patients who had legal access to medical marijuana, a new study finds.

In fact, Medicare saved more than $165 million in 2013 on prescription drugs in the District of Columbia and 17 states that allowed cannabis to be used as medicine, researchers calculated. If every state in the nation legalized medical marijuana, the study forecast that the federal program would save more than $468 million a year on pharmaceuticals for disabled Americans and those 65 and older.

No health insurance, including Medicare, will reimburse for the cost of marijuana. Although medical cannabis is legal today in 25 states and the District of Columbia, federal law continues to prohibit its prescription in all circumstances.

The new study, published July 6 in Health Affairs, was the first to ask if there's any evidence that medical marijuana is being used as medicine, said senior author W. David Bradford in a phone interview. The answer is yes, said Bradford, a health economist and a professor at the University of Georgia in Athens.

"When states turned on medical marijuana laws, we did see a rather substantial turn away from FDA-approved medicine," he said.

Researchers analyzed Medicare data from 2010 through 2013 for drugs approved by the U.S. Food and Drug Administration (FDA) to treat nine ailments - from pain to depression and nausea - for which marijuana might be an alternative remedy.

They expected to see fewer prescriptions for FDA-approved drugs that might treat the same conditions as cannabis. Indeed, except for glaucoma, doctors wrote fewer prescriptions for all nine ailments after medical marijuana laws took effect, the study found.

The number of Medicare prescriptions significantly dropped for drugs that treat pain, depression, anxiety, nausea, psychoses, seizures and sleep disorders.

For pain, the annual number of daily doses prescribed per physician fell by more than 11 percent.

"The results show that marijuana might be beneficial with diverting people away from opioids," Bradford said.

A 2014 study found that opioid overdose death rates were on average nearly 25 percent lower in states where medical marijuana was legal compared to states where it remained illegal. Chronic or severe pain is considered a primary indicator for medical marijuana in most states where it is legal.

Nearly two million Americans either abused or were dependent on prescription opioids in 2014, according to the U.S. Centers for Disease Control and Prevention (CDC). Since 1999, more than 165,000 Americans have died from prescription opioid overdoses.

Addiction psychiatrist Dr. Kevin Hill questioned whether medical marijuana patients might in some cases be getting inferior or incorrect treatment, and if so, whether the resulting extra healthcare costs would overshadow the Medicare drug savings. Hill, a professor at Harvard Medical School in Boston, was not involved in the new study.

"Fewer opioid prescriptions in medical marijuana states might be a good thing, but I am concerned about the overall quality of care delivered in medical marijuana specialty clinics," he told Reuters Health in an email.

He criticized the implementation of medical marijuana laws in many states as often leading to "medical care that is of poor quality."

Part of the problem stems from a dearth of research into the efficacy of medical marijuana.

Although California became the first state to legalize medical marijuana in 1996, federal law enacted by Congress in 1970 continues to put cannabis in the same category as heroin, Schedule 1 of the Comprehensive Drug Abuse Prevention and Control Act, and finds it has no medicinal value. Consequently, research has been severely limited.

Sheigla Murphy, a medical sociologist who was not involved in the current study, praised it as a major contribution to the literature on the role of medical marijuana in older adults.

Murphy directs the Center for Substance Abuse Studies in San Francisco and has done prior research on marijuana and baby boomers. She said some older adults prefer marijuana to painkillers and sleeping pills.

"It fits with the problems of older age, problems with sleeping, depression, arthritis, worn-out body parts that begin to hurt. Marijuana can relieve these without the side effects of grogginess and worrying about addiction," she said.

"As we're trying to reduce the number of pain medications, I think marijuana would be a welcome addition to the pharmacopeia," she said. "The one thing we know is no one has ever died of it."

SOURCE: http://bit.ly/1lx2GBv

Health Affairs 2016.

Physicians wrote significantly fewer prescriptions for painkillers and other medications for elderly and disabled patients who had legal access to medical marijuana, a new study finds.

In fact, Medicare saved more than $165 million in 2013 on prescription drugs in the District of Columbia and 17 states that allowed cannabis to be used as medicine, researchers calculated. If every state in the nation legalized medical marijuana, the study forecast that the federal program would save more than $468 million a year on pharmaceuticals for disabled Americans and those 65 and older.

No health insurance, including Medicare, will reimburse for the cost of marijuana. Although medical cannabis is legal today in 25 states and the District of Columbia, federal law continues to prohibit its prescription in all circumstances.

The new study, published July 6 in Health Affairs, was the first to ask if there's any evidence that medical marijuana is being used as medicine, said senior author W. David Bradford in a phone interview. The answer is yes, said Bradford, a health economist and a professor at the University of Georgia in Athens.

"When states turned on medical marijuana laws, we did see a rather substantial turn away from FDA-approved medicine," he said.

Researchers analyzed Medicare data from 2010 through 2013 for drugs approved by the U.S. Food and Drug Administration (FDA) to treat nine ailments - from pain to depression and nausea - for which marijuana might be an alternative remedy.

They expected to see fewer prescriptions for FDA-approved drugs that might treat the same conditions as cannabis. Indeed, except for glaucoma, doctors wrote fewer prescriptions for all nine ailments after medical marijuana laws took effect, the study found.

The number of Medicare prescriptions significantly dropped for drugs that treat pain, depression, anxiety, nausea, psychoses, seizures and sleep disorders.

For pain, the annual number of daily doses prescribed per physician fell by more than 11 percent.

"The results show that marijuana might be beneficial with diverting people away from opioids," Bradford said.

A 2014 study found that opioid overdose death rates were on average nearly 25 percent lower in states where medical marijuana was legal compared to states where it remained illegal. Chronic or severe pain is considered a primary indicator for medical marijuana in most states where it is legal.

Nearly two million Americans either abused or were dependent on prescription opioids in 2014, according to the U.S. Centers for Disease Control and Prevention (CDC). Since 1999, more than 165,000 Americans have died from prescription opioid overdoses.

Addiction psychiatrist Dr. Kevin Hill questioned whether medical marijuana patients might in some cases be getting inferior or incorrect treatment, and if so, whether the resulting extra healthcare costs would overshadow the Medicare drug savings. Hill, a professor at Harvard Medical School in Boston, was not involved in the new study.

"Fewer opioid prescriptions in medical marijuana states might be a good thing, but I am concerned about the overall quality of care delivered in medical marijuana specialty clinics," he told Reuters Health in an email.

He criticized the implementation of medical marijuana laws in many states as often leading to "medical care that is of poor quality."

Part of the problem stems from a dearth of research into the efficacy of medical marijuana.

Although California became the first state to legalize medical marijuana in 1996, federal law enacted by Congress in 1970 continues to put cannabis in the same category as heroin, Schedule 1 of the Comprehensive Drug Abuse Prevention and Control Act, and finds it has no medicinal value. Consequently, research has been severely limited.

Sheigla Murphy, a medical sociologist who was not involved in the current study, praised it as a major contribution to the literature on the role of medical marijuana in older adults.

Murphy directs the Center for Substance Abuse Studies in San Francisco and has done prior research on marijuana and baby boomers. She said some older adults prefer marijuana to painkillers and sleeping pills.

"It fits with the problems of older age, problems with sleeping, depression, arthritis, worn-out body parts that begin to hurt. Marijuana can relieve these without the side effects of grogginess and worrying about addiction," she said.

"As we're trying to reduce the number of pain medications, I think marijuana would be a welcome addition to the pharmacopeia," she said. "The one thing we know is no one has ever died of it."

SOURCE: http://bit.ly/1lx2GBv

Health Affairs 2016.

Physicians wrote significantly fewer prescriptions for painkillers and other medications for elderly and disabled patients who had legal access to medical marijuana, a new study finds.

In fact, Medicare saved more than $165 million in 2013 on prescription drugs in the District of Columbia and 17 states that allowed cannabis to be used as medicine, researchers calculated. If every state in the nation legalized medical marijuana, the study forecast that the federal program would save more than $468 million a year on pharmaceuticals for disabled Americans and those 65 and older.

No health insurance, including Medicare, will reimburse for the cost of marijuana. Although medical cannabis is legal today in 25 states and the District of Columbia, federal law continues to prohibit its prescription in all circumstances.

The new study, published July 6 in Health Affairs, was the first to ask if there's any evidence that medical marijuana is being used as medicine, said senior author W. David Bradford in a phone interview. The answer is yes, said Bradford, a health economist and a professor at the University of Georgia in Athens.

"When states turned on medical marijuana laws, we did see a rather substantial turn away from FDA-approved medicine," he said.

Researchers analyzed Medicare data from 2010 through 2013 for drugs approved by the U.S. Food and Drug Administration (FDA) to treat nine ailments - from pain to depression and nausea - for which marijuana might be an alternative remedy.

They expected to see fewer prescriptions for FDA-approved drugs that might treat the same conditions as cannabis. Indeed, except for glaucoma, doctors wrote fewer prescriptions for all nine ailments after medical marijuana laws took effect, the study found.

The number of Medicare prescriptions significantly dropped for drugs that treat pain, depression, anxiety, nausea, psychoses, seizures and sleep disorders.

For pain, the annual number of daily doses prescribed per physician fell by more than 11 percent.

"The results show that marijuana might be beneficial with diverting people away from opioids," Bradford said.

A 2014 study found that opioid overdose death rates were on average nearly 25 percent lower in states where medical marijuana was legal compared to states where it remained illegal. Chronic or severe pain is considered a primary indicator for medical marijuana in most states where it is legal.

Nearly two million Americans either abused or were dependent on prescription opioids in 2014, according to the U.S. Centers for Disease Control and Prevention (CDC). Since 1999, more than 165,000 Americans have died from prescription opioid overdoses.

Addiction psychiatrist Dr. Kevin Hill questioned whether medical marijuana patients might in some cases be getting inferior or incorrect treatment, and if so, whether the resulting extra healthcare costs would overshadow the Medicare drug savings. Hill, a professor at Harvard Medical School in Boston, was not involved in the new study.

"Fewer opioid prescriptions in medical marijuana states might be a good thing, but I am concerned about the overall quality of care delivered in medical marijuana specialty clinics," he told Reuters Health in an email.

He criticized the implementation of medical marijuana laws in many states as often leading to "medical care that is of poor quality."

Part of the problem stems from a dearth of research into the efficacy of medical marijuana.

Although California became the first state to legalize medical marijuana in 1996, federal law enacted by Congress in 1970 continues to put cannabis in the same category as heroin, Schedule 1 of the Comprehensive Drug Abuse Prevention and Control Act, and finds it has no medicinal value. Consequently, research has been severely limited.

Sheigla Murphy, a medical sociologist who was not involved in the current study, praised it as a major contribution to the literature on the role of medical marijuana in older adults.

Murphy directs the Center for Substance Abuse Studies in San Francisco and has done prior research on marijuana and baby boomers. She said some older adults prefer marijuana to painkillers and sleeping pills.

"It fits with the problems of older age, problems with sleeping, depression, arthritis, worn-out body parts that begin to hurt. Marijuana can relieve these without the side effects of grogginess and worrying about addiction," she said.

"As we're trying to reduce the number of pain medications, I think marijuana would be a welcome addition to the pharmacopeia," she said. "The one thing we know is no one has ever died of it."

SOURCE: http://bit.ly/1lx2GBv

Health Affairs 2016.

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.

NEW YORK - After a decade of follow-up in the Prostate Cancer Research International Active Surveillance (PRIAS) study, researchers have confirmed that active surveillance is a safe treatment option for men with low-risk prostate cancer.

"However," they say, "some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance."

Dr. Leonard P. Bokhorst of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues analyzed data on more than 5,000 men in 18 countries followed in PRIAS, including 622 who were followed more than five years and 107 were followed more than 7.5 years.

The median age at diagnosis was 65.9 years.

Original inclusion criteria included Gleason score 3+3 or lower, stage cT2c or lower, and prostate-specific antigen (PSA) 10 ng/ml or lower. PSA tests were scheduled every three months and digital rectal examinations were scheduled every six months during the first two years of study, then less often later. Criteria to recommend starting active treatment include Gleason score higher than 3+3, more than two positive cores, and stage higher than cT2.

Median PSA for the study population was 5.7 ng/ml. Most men (69%) had one positive biopsy core, with Gleason score of 3+3 (99%) and a clinical stage of T1c (88%).

Almost 3,400 men received at least one repeat biopsy during follow-up and some received up to five biopsies.

Overall, 1,768 men discontinued active surveillance during follow-up, 1,102 due to protocol-based reclassification. Other reasons for discontinuations included anxiety, switch to watchful waiting, death, and loss to follow-up. Two-thirds (67%) of the men were treated with either radical prostatectomy or radiation therapy after discontinuation. Only 3% received hormonal therapy.

Almost half (48%) of the patients were still on active surveillance after five years and 27% were on active surveillance at 10 years, the researchers reported online June 19 in European Urology.

The team had pathology data on 360 men who had radical prostatectomy. Of the men who switched to treatment because of protocol-based reclassification, 82 (30%) had favorable pathological outcomes, 85 (34%) had intermediate outcomes, and 100 (36%) had unfavorable outcomes.

Mortality from prostate cancer was less than 1% during follow-up.

Because of the higher rate of unfavorable treatment outcomes, the researchers recommended a change in the PRIAS protocol.

"Instead of an immediate switch to active treatment if more than two cores are positive, men should receive further investigation to confirm higher risk disease," the researchers write. They recommend examination by magnetic resonance imaging because its negative predictive value for Gleason upgrading is near 100%.

They concluded, "Criteria used to recommend a switch to active treatment do not seem selective enough to avoid unnecessary switches to active treatment."

Dr. Bokhorst did not respond to a request for comment.

The Prostate Cancer Research Foundation, Rotterdam, supports the PRIAS study. The authors made no disclosures.

SOURCE: http://bit.ly/28Q5Cd3

Eur Urol 2016.