Michele G. Sullivan

LOS ANGELES – As the economy worsens and the cost of drugs rises, more and more stroke survivors are forced to cut back on a critical health ally – prescription medications.

The rate of medication nonadherence due to cost in stroke survivors increased from 9% in 2002 to almost 12% by 2009, Dr. Deborah A. Levine reported Feb. 10 at the International Stroke Conference.

Medicare Part D – the program introduced in 2006 to address this problem – isn’t helping stroke survivors very much, said Dr. Levine, of the University of Michigan. In fact, her study found that cost-related medication nonadherence was actually twice as high in Medicare Part D enrollees than it was in those who did not have the prescription benefit.

The clinical implications can be severe, she said, from increasing the risk of recurrent stroke or heart attack to neglecting treatment of pre-existing conditions. "The crucial message for physicians is that we need to ask our patients [every time we see them] if they can afford their medications, and if they can’t we need to drastically modify their medication regimen. Patients are not able to effectively prioritize which medications [would] give the biggest bang for the buck, so I work with them to prioritize the regimen to the essential ones that will have the highest value and health benefit, such as antihypertensives," Dr. Levine said at the meeting, which was sponsored by the American Heart Association.

The average stroke survivor takes 11 medications, a number that includes those taken before the stroke and those prescribed to prevent another stroke or heart attack. "In my clinic, patients are typically on four additional drugs after their stroke for things including stroke complications like seizure, chronic pain, and depression and those to prevent another cardiovascular event. These are in addition to their previous drugs, which are typically for things like hypertension, lipids, and diabetes. And many require multiple drugs to control these conditions to the target levels."

Even though many of the medications have generic forms, not all generics are cheap, she pointed out. And with so many needed, the cost can rise alarmingly. "Even if the copay is only $5 or $10 for each medication, that can be more than some of our patients can afford."

Dr. Levine and her colleagues examined data from the National Health Interview Survey from the years 2006-2009. The survey interviews community-dwelling adults and then extrapolates the results to the entire U.S. population.

She compared these recent data to those obtained for a similar study that examined rates of nonadherence based on the survey conducted from 1998 to 2002 (Arch. Neurol. 2007; 64:37-42).

In both surveys, the question assessing cost-related nonadherence was "During the past 12 months, was there any time when you needed prescription medicines but didn’t get them because you couldn’t afford them?"

According to the 2006-2009 survey, there were 5.3 million stroke survivors aged 45 years or older. Of these, 3.6 million were Medicare beneficiaries, and of these, 1.5 million participated in Medicare Part D. The overall proportion of those who reported nonadherence due to cost was 12% – significantly higher than the 8.6% rate found in the 1998-2002 survey.

The results also varied significantly by age and insurance status. In the earlier study, 18% of patients aged 45-54 years reported cost-related nonadherence, compared with 30% in the later study – a significant increase. The differences were not statistically significant among other age groups up to 75 years and older.

Insurance status also significantly affected the situation. In the 1998-2002 survey, 39% of the uninsured reported the problem, compared with 60% of the uninsured in 2006-2009.

"We were very surprised to find that Medicare Part D enrollees had a significantly greater frequency of nonadherence due to cost than did Medicare Part D nonenrollees," Dr. Levine said. In the most recent survey, 12% of enrollees reported nonadherence, compared with 6% of those who did not participate in the program. "Despite this federal program, medication is still unaffordable for many stroke survivors and this prevents the translation of some remarkable research and public health advances to many of our stroke patients," she said.

Potential solutions might include physician screening for medication underuse in stroke patients, particularly the young, uninsured, and Medicare Part D participants, Dr. Levine suggested. "The proposed national affordable health insurance program would be expected to improve cost-related medication nonadherence, medication access, and provide free medicines to prevent recurrent strokes and heart attacks."

The cause of this problem, at least for Medicare Part D enrollees, appears to be the "doughnut hole problem," Dr. Levine said. "The Medicare Part D doughnut hole means that after the program covering $2,500 in medical expenditures, a beneficiary will incur the cost of medications up to $5,000, when catastrophic coverage kicks in, after which Medicare Part D picks up the cost. The new national new health reforms proposed to close that by 2020."

Studies have shown that stroke survivors have a very high risk of both entering and leaving that hole in coverage, she added; survivors spend an average of $800 per month on medications. Because of this high monthly cost, stroke survivors are at a two- to threefold increased risk of severe financial burden, compared with those with other chronic illnesses, such as diabetes or cardiovascular disease.

"For our patients, the important message is that they need to take their medications to prevent a recurrent stroke or cardiovascular event," she said. "If they can’t get the medications due to cost, patients need to tell their doctor and enter a dialogue in order to solve the problem."

Dr. Levine and her colleagues did not report any financial disclosures.

LOS ANGELES – As the economy worsens and the cost of drugs rises, more and more stroke survivors are forced to cut back on a critical health ally – prescription medications.

The rate of medication nonadherence due to cost in stroke survivors increased from 9% in 2002 to almost 12% by 2009, Dr. Deborah A. Levine reported Feb. 10 at the International Stroke Conference.

Medicare Part D – the program introduced in 2006 to address this problem – isn’t helping stroke survivors very much, said Dr. Levine, of the University of Michigan. In fact, her study found that cost-related medication nonadherence was actually twice as high in Medicare Part D enrollees than it was in those who did not have the prescription benefit.

The clinical implications can be severe, she said, from increasing the risk of recurrent stroke or heart attack to neglecting treatment of pre-existing conditions. "The crucial message for physicians is that we need to ask our patients [every time we see them] if they can afford their medications, and if they can’t we need to drastically modify their medication regimen. Patients are not able to effectively prioritize which medications [would] give the biggest bang for the buck, so I work with them to prioritize the regimen to the essential ones that will have the highest value and health benefit, such as antihypertensives," Dr. Levine said at the meeting, which was sponsored by the American Heart Association.

The average stroke survivor takes 11 medications, a number that includes those taken before the stroke and those prescribed to prevent another stroke or heart attack. "In my clinic, patients are typically on four additional drugs after their stroke for things including stroke complications like seizure, chronic pain, and depression and those to prevent another cardiovascular event. These are in addition to their previous drugs, which are typically for things like hypertension, lipids, and diabetes. And many require multiple drugs to control these conditions to the target levels."

Even though many of the medications have generic forms, not all generics are cheap, she pointed out. And with so many needed, the cost can rise alarmingly. "Even if the copay is only $5 or $10 for each medication, that can be more than some of our patients can afford."

Dr. Levine and her colleagues examined data from the National Health Interview Survey from the years 2006-2009. The survey interviews community-dwelling adults and then extrapolates the results to the entire U.S. population.

She compared these recent data to those obtained for a similar study that examined rates of nonadherence based on the survey conducted from 1998 to 2002 (Arch. Neurol. 2007; 64:37-42).

In both surveys, the question assessing cost-related nonadherence was "During the past 12 months, was there any time when you needed prescription medicines but didn’t get them because you couldn’t afford them?"

According to the 2006-2009 survey, there were 5.3 million stroke survivors aged 45 years or older. Of these, 3.6 million were Medicare beneficiaries, and of these, 1.5 million participated in Medicare Part D. The overall proportion of those who reported nonadherence due to cost was 12% – significantly higher than the 8.6% rate found in the 1998-2002 survey.

The results also varied significantly by age and insurance status. In the earlier study, 18% of patients aged 45-54 years reported cost-related nonadherence, compared with 30% in the later study – a significant increase. The differences were not statistically significant among other age groups up to 75 years and older.

Insurance status also significantly affected the situation. In the 1998-2002 survey, 39% of the uninsured reported the problem, compared with 60% of the uninsured in 2006-2009.

"We were very surprised to find that Medicare Part D enrollees had a significantly greater frequency of nonadherence due to cost than did Medicare Part D nonenrollees," Dr. Levine said. In the most recent survey, 12% of enrollees reported nonadherence, compared with 6% of those who did not participate in the program. "Despite this federal program, medication is still unaffordable for many stroke survivors and this prevents the translation of some remarkable research and public health advances to many of our stroke patients," she said.

Potential solutions might include physician screening for medication underuse in stroke patients, particularly the young, uninsured, and Medicare Part D participants, Dr. Levine suggested. "The proposed national affordable health insurance program would be expected to improve cost-related medication nonadherence, medication access, and provide free medicines to prevent recurrent strokes and heart attacks."

The cause of this problem, at least for Medicare Part D enrollees, appears to be the "doughnut hole problem," Dr. Levine said. "The Medicare Part D doughnut hole means that after the program covering $2,500 in medical expenditures, a beneficiary will incur the cost of medications up to $5,000, when catastrophic coverage kicks in, after which Medicare Part D picks up the cost. The new national new health reforms proposed to close that by 2020."

Studies have shown that stroke survivors have a very high risk of both entering and leaving that hole in coverage, she added; survivors spend an average of $800 per month on medications. Because of this high monthly cost, stroke survivors are at a two- to threefold increased risk of severe financial burden, compared with those with other chronic illnesses, such as diabetes or cardiovascular disease.

"For our patients, the important message is that they need to take their medications to prevent a recurrent stroke or cardiovascular event," she said. "If they can’t get the medications due to cost, patients need to tell their doctor and enter a dialogue in order to solve the problem."

Dr. Levine and her colleagues did not report any financial disclosures.

LOS ANGELES – As the economy worsens and the cost of drugs rises, more and more stroke survivors are forced to cut back on a critical health ally – prescription medications.

The rate of medication nonadherence due to cost in stroke survivors increased from 9% in 2002 to almost 12% by 2009, Dr. Deborah A. Levine reported Feb. 10 at the International Stroke Conference.

Medicare Part D – the program introduced in 2006 to address this problem – isn’t helping stroke survivors very much, said Dr. Levine, of the University of Michigan. In fact, her study found that cost-related medication nonadherence was actually twice as high in Medicare Part D enrollees than it was in those who did not have the prescription benefit.

The clinical implications can be severe, she said, from increasing the risk of recurrent stroke or heart attack to neglecting treatment of pre-existing conditions. "The crucial message for physicians is that we need to ask our patients [every time we see them] if they can afford their medications, and if they can’t we need to drastically modify their medication regimen. Patients are not able to effectively prioritize which medications [would] give the biggest bang for the buck, so I work with them to prioritize the regimen to the essential ones that will have the highest value and health benefit, such as antihypertensives," Dr. Levine said at the meeting, which was sponsored by the American Heart Association.

The average stroke survivor takes 11 medications, a number that includes those taken before the stroke and those prescribed to prevent another stroke or heart attack. "In my clinic, patients are typically on four additional drugs after their stroke for things including stroke complications like seizure, chronic pain, and depression and those to prevent another cardiovascular event. These are in addition to their previous drugs, which are typically for things like hypertension, lipids, and diabetes. And many require multiple drugs to control these conditions to the target levels."

Even though many of the medications have generic forms, not all generics are cheap, she pointed out. And with so many needed, the cost can rise alarmingly. "Even if the copay is only $5 or $10 for each medication, that can be more than some of our patients can afford."

Dr. Levine and her colleagues examined data from the National Health Interview Survey from the years 2006-2009. The survey interviews community-dwelling adults and then extrapolates the results to the entire U.S. population.

She compared these recent data to those obtained for a similar study that examined rates of nonadherence based on the survey conducted from 1998 to 2002 (Arch. Neurol. 2007; 64:37-42).

In both surveys, the question assessing cost-related nonadherence was "During the past 12 months, was there any time when you needed prescription medicines but didn’t get them because you couldn’t afford them?"

According to the 2006-2009 survey, there were 5.3 million stroke survivors aged 45 years or older. Of these, 3.6 million were Medicare beneficiaries, and of these, 1.5 million participated in Medicare Part D. The overall proportion of those who reported nonadherence due to cost was 12% – significantly higher than the 8.6% rate found in the 1998-2002 survey.

The results also varied significantly by age and insurance status. In the earlier study, 18% of patients aged 45-54 years reported cost-related nonadherence, compared with 30% in the later study – a significant increase. The differences were not statistically significant among other age groups up to 75 years and older.

Insurance status also significantly affected the situation. In the 1998-2002 survey, 39% of the uninsured reported the problem, compared with 60% of the uninsured in 2006-2009.

"We were very surprised to find that Medicare Part D enrollees had a significantly greater frequency of nonadherence due to cost than did Medicare Part D nonenrollees," Dr. Levine said. In the most recent survey, 12% of enrollees reported nonadherence, compared with 6% of those who did not participate in the program. "Despite this federal program, medication is still unaffordable for many stroke survivors and this prevents the translation of some remarkable research and public health advances to many of our stroke patients," she said.

Potential solutions might include physician screening for medication underuse in stroke patients, particularly the young, uninsured, and Medicare Part D participants, Dr. Levine suggested. "The proposed national affordable health insurance program would be expected to improve cost-related medication nonadherence, medication access, and provide free medicines to prevent recurrent strokes and heart attacks."

The cause of this problem, at least for Medicare Part D enrollees, appears to be the "doughnut hole problem," Dr. Levine said. "The Medicare Part D doughnut hole means that after the program covering $2,500 in medical expenditures, a beneficiary will incur the cost of medications up to $5,000, when catastrophic coverage kicks in, after which Medicare Part D picks up the cost. The new national new health reforms proposed to close that by 2020."

Studies have shown that stroke survivors have a very high risk of both entering and leaving that hole in coverage, she added; survivors spend an average of $800 per month on medications. Because of this high monthly cost, stroke survivors are at a two- to threefold increased risk of severe financial burden, compared with those with other chronic illnesses, such as diabetes or cardiovascular disease.

"For our patients, the important message is that they need to take their medications to prevent a recurrent stroke or cardiovascular event," she said. "If they can’t get the medications due to cost, patients need to tell their doctor and enter a dialogue in order to solve the problem."

Dr. Levine and her colleagues did not report any financial disclosures.

LOS ANGELES – The use of clot-busting drugs in patients with mild stroke could save thousands of them from long-term stroke-related disability, and about $200 million each year in stroke-related health care costs.

The decision to administer tissue plasminogen activator (tPA) to patients with mild stroke is a difficult one, balancing the possible benefits with the risk of further bleeding, Dr. Pooja Khatri said during a press briefing at the International Stroke Conference. But her epidemiologic study of 150 mild strokes – only four of which were treated with tPA – suggests that administering the drug could prevent the disability that affects up to one-third of these patients.

Her retrospective study drew its data from the Greater Cincinnati/Northern Kentucky Stroke Study. The database included 441 patients in that region who were treated for ischemic stroke during 2005. Of those, 56% (247) had strokes that were considered mild, with a baseline modified Rankin Scale score of 2-6. And, of those patients, 62% (150) were considered eligible for tPA treatment; however, only 1% (4) received the drug.

Dr. Khatri, director of acute stroke at the University of Cincinnati Academic Health Center, did not follow the patients to compare clinical outcomes over time. However, she said, based on two extant studies, about 30% of mild stroke patients do experience deficits that affect their lives. "These tend to be on the milder end of the spectrum, but it’s still disability," she said in an interview. "They might not able to drive, go back to work, or take care of themselves. They can still walk, but they are not the same person they used to be."

She extrapolated her findings to the entire U.S. population in 2010, estimating that mild strokes would have occurred in 27,203 patients without baseline disability. If all of the these patients had received an effective treatment, such as the current clot-busting drugs or a milder form that could be developed, up to 13% (3,761) could be saved from disabling stroke-related disability.

The estimated annual cost savings could be immense, she said. "We could see a savings of $200 million across the country," an estimate that includes the potential costs of adverse events associated with widening the treated population.

But her data don’t directly address the day-to-day decisions clinicians have to make when faced with a mild stroke patient. A tiny fraction of mild stroke patients receive tPA treatment, she said, because generally the potential gains are regarded as small, compared with the risk of aggravated brain hemorrhage. Most of the time, things go well when treating mild stroke patients, because the risk of bleeding lessens with stroke severity. "But sometimes we get burned," Dr. Khatri said. "That [untreated] patient may end up being paralyzed on one side or having cognitive problems that we didn’t recognize in the emergency department. On the other hand, we may treat and that patient can bleed and perhaps even die." The dilemma can be answered only by a large, randomized trial, she said – something she and her colleagues at the University of Cincinnati are trying to get started.

"Our group is planning such a study, to randomize those with mild stroke to tPA or placebo and then follow them, characterizing their hemorrhage rates as well as their disability outcomes."

Dr. Khatri’s study was sponsored by the National Institutes of Health; neither she nor any coauthors had any financial disclosures.

LOS ANGELES – The use of clot-busting drugs in patients with mild stroke could save thousands of them from long-term stroke-related disability, and about $200 million each year in stroke-related health care costs.

The decision to administer tissue plasminogen activator (tPA) to patients with mild stroke is a difficult one, balancing the possible benefits with the risk of further bleeding, Dr. Pooja Khatri said during a press briefing at the International Stroke Conference. But her epidemiologic study of 150 mild strokes – only four of which were treated with tPA – suggests that administering the drug could prevent the disability that affects up to one-third of these patients.

Her retrospective study drew its data from the Greater Cincinnati/Northern Kentucky Stroke Study. The database included 441 patients in that region who were treated for ischemic stroke during 2005. Of those, 56% (247) had strokes that were considered mild, with a baseline modified Rankin Scale score of 2-6. And, of those patients, 62% (150) were considered eligible for tPA treatment; however, only 1% (4) received the drug.

Dr. Khatri, director of acute stroke at the University of Cincinnati Academic Health Center, did not follow the patients to compare clinical outcomes over time. However, she said, based on two extant studies, about 30% of mild stroke patients do experience deficits that affect their lives. "These tend to be on the milder end of the spectrum, but it’s still disability," she said in an interview. "They might not able to drive, go back to work, or take care of themselves. They can still walk, but they are not the same person they used to be."

She extrapolated her findings to the entire U.S. population in 2010, estimating that mild strokes would have occurred in 27,203 patients without baseline disability. If all of the these patients had received an effective treatment, such as the current clot-busting drugs or a milder form that could be developed, up to 13% (3,761) could be saved from disabling stroke-related disability.

The estimated annual cost savings could be immense, she said. "We could see a savings of $200 million across the country," an estimate that includes the potential costs of adverse events associated with widening the treated population.

But her data don’t directly address the day-to-day decisions clinicians have to make when faced with a mild stroke patient. A tiny fraction of mild stroke patients receive tPA treatment, she said, because generally the potential gains are regarded as small, compared with the risk of aggravated brain hemorrhage. Most of the time, things go well when treating mild stroke patients, because the risk of bleeding lessens with stroke severity. "But sometimes we get burned," Dr. Khatri said. "That [untreated] patient may end up being paralyzed on one side or having cognitive problems that we didn’t recognize in the emergency department. On the other hand, we may treat and that patient can bleed and perhaps even die." The dilemma can be answered only by a large, randomized trial, she said – something she and her colleagues at the University of Cincinnati are trying to get started.

"Our group is planning such a study, to randomize those with mild stroke to tPA or placebo and then follow them, characterizing their hemorrhage rates as well as their disability outcomes."

Dr. Khatri’s study was sponsored by the National Institutes of Health; neither she nor any coauthors had any financial disclosures.

LOS ANGELES – The use of clot-busting drugs in patients with mild stroke could save thousands of them from long-term stroke-related disability, and about $200 million each year in stroke-related health care costs.

The decision to administer tissue plasminogen activator (tPA) to patients with mild stroke is a difficult one, balancing the possible benefits with the risk of further bleeding, Dr. Pooja Khatri said during a press briefing at the International Stroke Conference. But her epidemiologic study of 150 mild strokes – only four of which were treated with tPA – suggests that administering the drug could prevent the disability that affects up to one-third of these patients.

Her retrospective study drew its data from the Greater Cincinnati/Northern Kentucky Stroke Study. The database included 441 patients in that region who were treated for ischemic stroke during 2005. Of those, 56% (247) had strokes that were considered mild, with a baseline modified Rankin Scale score of 2-6. And, of those patients, 62% (150) were considered eligible for tPA treatment; however, only 1% (4) received the drug.

Dr. Khatri, director of acute stroke at the University of Cincinnati Academic Health Center, did not follow the patients to compare clinical outcomes over time. However, she said, based on two extant studies, about 30% of mild stroke patients do experience deficits that affect their lives. "These tend to be on the milder end of the spectrum, but it’s still disability," she said in an interview. "They might not able to drive, go back to work, or take care of themselves. They can still walk, but they are not the same person they used to be."

She extrapolated her findings to the entire U.S. population in 2010, estimating that mild strokes would have occurred in 27,203 patients without baseline disability. If all of the these patients had received an effective treatment, such as the current clot-busting drugs or a milder form that could be developed, up to 13% (3,761) could be saved from disabling stroke-related disability.

The estimated annual cost savings could be immense, she said. "We could see a savings of $200 million across the country," an estimate that includes the potential costs of adverse events associated with widening the treated population.

But her data don’t directly address the day-to-day decisions clinicians have to make when faced with a mild stroke patient. A tiny fraction of mild stroke patients receive tPA treatment, she said, because generally the potential gains are regarded as small, compared with the risk of aggravated brain hemorrhage. Most of the time, things go well when treating mild stroke patients, because the risk of bleeding lessens with stroke severity. "But sometimes we get burned," Dr. Khatri said. "That [untreated] patient may end up being paralyzed on one side or having cognitive problems that we didn’t recognize in the emergency department. On the other hand, we may treat and that patient can bleed and perhaps even die." The dilemma can be answered only by a large, randomized trial, she said – something she and her colleagues at the University of Cincinnati are trying to get started.

"Our group is planning such a study, to randomize those with mild stroke to tPA or placebo and then follow them, characterizing their hemorrhage rates as well as their disability outcomes."

Dr. Khatri’s study was sponsored by the National Institutes of Health; neither she nor any coauthors had any financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

SAN DIEGO – Aggressive skin cancers can recur, spread, and kill – and these lesions deserve special consideration after even an apparently successful Mohs procedure.

"Mohs is especially well suited to identify the rare patient who has a high-risk profile for local recurrence or metastasis," Dr. David Hodgens said at a meeting sponsored by the American Society for Mohs Surgery. "We can work together to develop radiotherapy techniques that treat both the primary site and the nodal basins to minimize toxicity and give the patient a better chance of a cure."

The Mohs surgeon is unlikely to see many patients who will need postoperative radiotherapy, said Dr. Hodgens, director of radiation oncology at Scripps Memorial Hospital, La Jolla, Calif. "Keep in mind the vast majority of patients will not need this – but be on the lookout for those who might."

Any skin cancer – squamous or basal cell carcinoma, Merkel cell tumor, melanoma or angiosarcoma – can be increasingly dangerous if certain risk factors are present, Dr. Hodgens said. Risk factors for local recurrence or metastatic spread include a lesion size greater than 2 cm; depth greater then 4 mm or a Clark level IV-V; location on the ear or lip, or within a scar; or perineural or periosteal invasion. Immunosuppressed patients are at particularly high risk, as are those with an already recurrent lesion. "A lesion that has recurred after prior treatment is one of the greatest risks of further recurrence or metastatic spread," he stressed.

Electron beam radiation is the best treatment for high-risk skin cancers. "Electrons are essential in treating the postoperative Mohs patient. If your radiation oncologist is not using electrons, find one who is," he said.

High-energy x-rays are also used, but mostly to cover a nodal basin where spread is suspected. But electrons have a unique property that allows a narrow beam to deliver 90% of its energy to a prespecified depth and then very rapidly decrease that energy as the beam goes deeper into the tissue. "Electrons provide penetration to a desired depth without the through transmission of x-rays," Dr. Hodgens said.

Post-Mohs radiation calls for a large treatment field that encompasses the entire surgical field and generous margins. "We try to get at least 2 cm around the surgical bed," he said. Patients typically receive daily treatments for 5-7 weeks, with 1.8-2 Gy/day to the primary site. The total radiation dose is usually around 50-60 Gy.

"We treat them as seriously as we do any of our patients with breast, lung, or brain tumors," Dr. Hodgens said. "They have the potential to die of their skin cancer. This is a long aggressive course of treatment designed to give the best chance of cure."

X-rays can be added to treat the associated nodal basin, if nodal spread is a concern. "The toxicity of adding nodal radiation is minimal," Dr. Hodgens said. "It’s very well tolerated, with mostly just mild erythema. It’s really an easy thing to do and very worthwhile."

There are few studies published on postoperative radiation for strict indications after well-performed Mohs surgery. Most recently, a Greek study of 315 patients found that post-Mohs radiation was associated with a 92% reduced risk of recurrence (Eur. J. Cancer 2010;46:1563-72).

Last year, an Australian study of 118 patients with cutaneous head or neck cancers found that surgery plus radiotherapy improved survival rates, even among those with perineural involvement – a very poor prognostic factor. The 5-year local control rates were 90% for those with histologically proven perineural involvement and 57% for those with symptoms of perineural involvement (Head Neck 2009;31:604-10)

Dr. Hodgens had no financial disclosures.

Major Finding: Among 36 pregnancies, 14 subjects needed no additional thyroxine to maintain adequate suppression; 22 needed dosage increases and, of those, 4 were still not adequately suppressed during the entire pregnancy.

Data Source: Prospective study of thyroid function testing at 4-6 weeks throughout 36 pregnancies in 28 women.

Disclosures: Dr. Besic had no relevant financial disclosures.

PARIS – Frequent thyroid function tests during pregnancy can ensure that thyroid-stimulating hormone levels are optimally suppressed in women with a history of thyroid cancer.

In a small prospective study, TSH was adequately suppressed without dose adjustments in 39% of 36 pregnancies in 28 women. In the other pregnancies, additional thyroxine was needed as pregnancy progressed. This variability suggests that women who have undergone a total thyroidectomy experience a wide range of changes in TSH concentration throughout pregnancy, and argues for frequent monitoring and thyroxine dosage adjustment, according to Dr. Nikola Besic.

“This is why we perform thyroid function tests every 4-6 weeks in these women,” said Dr. Besic of the Institute of Oncology, Ljubljana, Slovenia. “This gives us the opportunity to change doses quickly and prevent elevation of the TSH.”

All 28 women in the study had undergone a total thyroidectomy followed by radioiodine ablation, and all were on suppressive doses of levothyroxine.

Thyroid function tests were performed before pregnancy, every 6-8 weeks during pregnancy, and after pregnancy. Adequate suppression was considered to be a TSH of 0.01-0.29 mU/L and a free T3 in the normal range.

Before conception, the group's mean TSH level was 0.9 mU/L. With pregnancy, the mean level rose to 2.01 mU/L in the second trimester, 1.46 mU/L in the third, and fell to 0.05 mU/L after delivery.

Before conception, the mean levothyroxine dose was 139 mcg daily. TSH remained adequately suppressed on the woman's baseline dosage in 14 pregnancies (39%); these women were taking a mean daily dose of 139 mcg.

In the remaining 22 pregnancies (61%), thyroxine dose had to be increased over time. The mean dose was 141 mcg in the first trimester, 150 mcg in the second, and 171 mcg in the third. After delivery, the mean dose was 156 mcg daily. The mean dose change necessary to maintain adequate TSH suppression throughout pregnancy was 31 mcg.

Dosing changes did not ensure adequate suppression at all times; 23% of pregnancies were adequately suppressed at all times during gestation, Dr. Besic said. “In these 22 pregnancies, TSH concentration remained suppressed in 4 pregnancies, in the normal range in 13, and elevated in 5.”

During the discussion period, panel chairman Dr. Bryan McIver of the Mayo Clinic, Rochester, Minn., asked about the common practice of automatically giving a 25- to 30-mcg increase in levothyroxine dose after conception, rather than performing consecutive thyroid function tests throughout pregnancy in women with a history of thyroid cancer.

Dr Besic said that more than one-third of the patients in his study did not need an increase in their dosage to maintain suppression. “However, TSH should not be elevated at all during pregnancy, and in our patients, despite our attempt to increase the dosage, some still had elevated levels.”

Major Finding: Among 36 pregnancies, 14 subjects needed no additional thyroxine to maintain adequate suppression; 22 needed dosage increases and, of those, 4 were still not adequately suppressed during the entire pregnancy.

Data Source: Prospective study of thyroid function testing at 4-6 weeks throughout 36 pregnancies in 28 women.

Disclosures: Dr. Besic had no relevant financial disclosures.

PARIS – Frequent thyroid function tests during pregnancy can ensure that thyroid-stimulating hormone levels are optimally suppressed in women with a history of thyroid cancer.

In a small prospective study, TSH was adequately suppressed without dose adjustments in 39% of 36 pregnancies in 28 women. In the other pregnancies, additional thyroxine was needed as pregnancy progressed. This variability suggests that women who have undergone a total thyroidectomy experience a wide range of changes in TSH concentration throughout pregnancy, and argues for frequent monitoring and thyroxine dosage adjustment, according to Dr. Nikola Besic.

“This is why we perform thyroid function tests every 4-6 weeks in these women,” said Dr. Besic of the Institute of Oncology, Ljubljana, Slovenia. “This gives us the opportunity to change doses quickly and prevent elevation of the TSH.”

All 28 women in the study had undergone a total thyroidectomy followed by radioiodine ablation, and all were on suppressive doses of levothyroxine.

Thyroid function tests were performed before pregnancy, every 6-8 weeks during pregnancy, and after pregnancy. Adequate suppression was considered to be a TSH of 0.01-0.29 mU/L and a free T3 in the normal range.

Before conception, the group's mean TSH level was 0.9 mU/L. With pregnancy, the mean level rose to 2.01 mU/L in the second trimester, 1.46 mU/L in the third, and fell to 0.05 mU/L after delivery.

Before conception, the mean levothyroxine dose was 139 mcg daily. TSH remained adequately suppressed on the woman's baseline dosage in 14 pregnancies (39%); these women were taking a mean daily dose of 139 mcg.

In the remaining 22 pregnancies (61%), thyroxine dose had to be increased over time. The mean dose was 141 mcg in the first trimester, 150 mcg in the second, and 171 mcg in the third. After delivery, the mean dose was 156 mcg daily. The mean dose change necessary to maintain adequate TSH suppression throughout pregnancy was 31 mcg.

Dosing changes did not ensure adequate suppression at all times; 23% of pregnancies were adequately suppressed at all times during gestation, Dr. Besic said. “In these 22 pregnancies, TSH concentration remained suppressed in 4 pregnancies, in the normal range in 13, and elevated in 5.”

During the discussion period, panel chairman Dr. Bryan McIver of the Mayo Clinic, Rochester, Minn., asked about the common practice of automatically giving a 25- to 30-mcg increase in levothyroxine dose after conception, rather than performing consecutive thyroid function tests throughout pregnancy in women with a history of thyroid cancer.

Dr Besic said that more than one-third of the patients in his study did not need an increase in their dosage to maintain suppression. “However, TSH should not be elevated at all during pregnancy, and in our patients, despite our attempt to increase the dosage, some still had elevated levels.”

Major Finding: Among 36 pregnancies, 14 subjects needed no additional thyroxine to maintain adequate suppression; 22 needed dosage increases and, of those, 4 were still not adequately suppressed during the entire pregnancy.

Data Source: Prospective study of thyroid function testing at 4-6 weeks throughout 36 pregnancies in 28 women.

Disclosures: Dr. Besic had no relevant financial disclosures.

PARIS – Frequent thyroid function tests during pregnancy can ensure that thyroid-stimulating hormone levels are optimally suppressed in women with a history of thyroid cancer.

In a small prospective study, TSH was adequately suppressed without dose adjustments in 39% of 36 pregnancies in 28 women. In the other pregnancies, additional thyroxine was needed as pregnancy progressed. This variability suggests that women who have undergone a total thyroidectomy experience a wide range of changes in TSH concentration throughout pregnancy, and argues for frequent monitoring and thyroxine dosage adjustment, according to Dr. Nikola Besic.

“This is why we perform thyroid function tests every 4-6 weeks in these women,” said Dr. Besic of the Institute of Oncology, Ljubljana, Slovenia. “This gives us the opportunity to change doses quickly and prevent elevation of the TSH.”

All 28 women in the study had undergone a total thyroidectomy followed by radioiodine ablation, and all were on suppressive doses of levothyroxine.

Thyroid function tests were performed before pregnancy, every 6-8 weeks during pregnancy, and after pregnancy. Adequate suppression was considered to be a TSH of 0.01-0.29 mU/L and a free T3 in the normal range.

Before conception, the group's mean TSH level was 0.9 mU/L. With pregnancy, the mean level rose to 2.01 mU/L in the second trimester, 1.46 mU/L in the third, and fell to 0.05 mU/L after delivery.

Before conception, the mean levothyroxine dose was 139 mcg daily. TSH remained adequately suppressed on the woman's baseline dosage in 14 pregnancies (39%); these women were taking a mean daily dose of 139 mcg.

In the remaining 22 pregnancies (61%), thyroxine dose had to be increased over time. The mean dose was 141 mcg in the first trimester, 150 mcg in the second, and 171 mcg in the third. After delivery, the mean dose was 156 mcg daily. The mean dose change necessary to maintain adequate TSH suppression throughout pregnancy was 31 mcg.

Dosing changes did not ensure adequate suppression at all times; 23% of pregnancies were adequately suppressed at all times during gestation, Dr. Besic said. “In these 22 pregnancies, TSH concentration remained suppressed in 4 pregnancies, in the normal range in 13, and elevated in 5.”

During the discussion period, panel chairman Dr. Bryan McIver of the Mayo Clinic, Rochester, Minn., asked about the common practice of automatically giving a 25- to 30-mcg increase in levothyroxine dose after conception, rather than performing consecutive thyroid function tests throughout pregnancy in women with a history of thyroid cancer.

Dr Besic said that more than one-third of the patients in his study did not need an increase in their dosage to maintain suppression. “However, TSH should not be elevated at all during pregnancy, and in our patients, despite our attempt to increase the dosage, some still had elevated levels.”

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

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Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Positron-emission tomography in combination with the radiolabeled compound florbetapir F-18 detected beta-amyloid plaques with 93% sensitivity and 100% specificity in the brains of 35 elderly patients, most of whom had some form of dementia.

Lead investigator Dr. Christopher Clark and his colleagues wrote that florbetapir-PET imaging could be an important diagnostic tool for Alzheimer's disease – perhaps with the ability to detect brain plaques early in a prodromal stage of the disease – and to measure plaque changes in relation to therapeutic response in future drug studies, according to Dr. Clark, medical director of Avid Radiopharmaceuticals, the company testing the compound (JAMA 2011;305:275-83).

The study also represents the first time an amyloid imaging agent has been tested against autopsy results, said coinvestigator Dr. Marwan N. Sabbagh, founding director of the Cleo Roberts Center for Clinical Research in Sun City, Ariz.

“It's really exciting to be able to correlate imaging so strongly with autopsy findings,” Dr. Sabbagh said.

But Dr. Clark and his coinvestigators cautioned that the study does not make it clear what specific clinical applications the imaging procedure could have, be it the clinical diagnosis of Alzheimer's disease or the prediction of progression to dementia.

The Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee will meet on Jan. 20 to discuss the compound and the study's findings.

Like Pittsburgh imaging compound B (PiB), florbetapir binds to beta-amyloid plaques in the living brain.

PiB's use, however, has been limited by its short half-life of 20 minutes.

Florbetapir achieves maximum uptake at 30 minutes and remains unchanged for the next 60 minutes, “providing a wide time window to obtain a 10-minute image,” the authors noted.

The prospective study involved 35 patients in hospice or long-term care facilities who were expected to die within 6 months.

Six of the patients were used to validate the imaging procedure while the remaining 29 were used in the primary validation study.

Among the 29 in the validation analysis, the mean age was 80 years.

This group included 13 with a clinical diagnosis of Alzheimer's, 5 with other dementias, 9 with normal cognition, and the rest with mild cognitive impairment.

Their mean Mini-Mental State Examination (MMSE) score was 3.8.

The control group comprised 74 young, healthy subjects, 27 of whom were positive for the APOE e4 allele, which greatly increases the risk of developing Alzheimer's in later life.

The control subjects had a mean age of 27 years and a mean MMSE score of 29.7.

Florbetapir imaging was negative for all 74 subjects, including those with the APOE e4 allele.

Florbetapir-PET imaging in the 35 patients was significantly correlated with both immunohistochemistry and silver stain for beta-amyloid plaques in each of the six brain regions that the investigators examined (frontal, temporal, parietal, anterior and posterior cingulate, precuneus, and cerebellum).

At autopsy, 15 patients in the validation group met pathologic criteria for Alzheimer's disease.

Of these, 14 had positive florbetapir-PET scans, leading to a sensitivity of 93%.

The other 14 patients had low levels of beta-amyloid plaque on autopsy, and did not meet the diagnostic criteria for Alzheimer's.

All 14 also had negative florbetapir-PET scans, giving 100% specificity.

“The neuropathological diagnosis in the participants who did not meet pathological criteria for AD included dementia with Lewy bodies, hippocampal sclerosis, Parkinson's disease, subcortical microscopic infarct, mesial temporal lobe neurofibrillary tangles, neurofibrillary tangles with argyrophilic grains and glial tauopathy, and no neuropathology,” the authors wrote.

Of the 15 patients in the validation cohort who had a clinical diagnosis of dementia during life, 3 did not have the same diagnosis on autopsy.

One of these patients had a clinical diagnosis of probable Alzheimer's but did not have it on autopsy, whereas one with a clinical diagnosis of Parkinson's disease dementia and one with a clinical diagnosis of Lewy body dementia actually had Alzheimer's.

Florbetapir-PET correctly predicted the presence or absence of Alzheimer's disease in these patients.

The authors noted that the patient sample used in the study did not represent a typical clinical population, most of whom would be referred for initial signs of cognitive impairment.

Rather, the cohort was selected “for their unique ability to provide information about the ability of florbetapir-PET imaging to accurately identify and quantify beta-amyloid with the shortest interval between imaging and definitive pathological evaluation possible,” they said.

The study was funded primarily by Avid Radiopharmaceuticals. Dr. Clark and eight of the coauthors are stockholders and/or employees of the company. All of the other coauthors received research grants, and most are educators, paid investigators, or members of the speakers bureau for Avid or for Eli Lilly, which acquired the company last November.

Positron-emission tomography in combination with the radiolabeled compound florbetapir F-18 detected beta-amyloid plaques with 93% sensitivity and 100% specificity in the brains of 35 elderly patients, most of whom had some form of dementia.

Lead investigator Dr. Christopher Clark and his colleagues wrote that florbetapir-PET imaging could be an important diagnostic tool for Alzheimer's disease – perhaps with the ability to detect brain plaques early in a prodromal stage of the disease – and to measure plaque changes in relation to therapeutic response in future drug studies, according to Dr. Clark, medical director of Avid Radiopharmaceuticals, the company testing the compound (JAMA 2011;305:275-83).

The study also represents the first time an amyloid imaging agent has been tested against autopsy results, said coinvestigator Dr. Marwan N. Sabbagh, founding director of the Cleo Roberts Center for Clinical Research in Sun City, Ariz.

“It's really exciting to be able to correlate imaging so strongly with autopsy findings,” Dr. Sabbagh said.

But Dr. Clark and his coinvestigators cautioned that the study does not make it clear what specific clinical applications the imaging procedure could have, be it the clinical diagnosis of Alzheimer's disease or the prediction of progression to dementia.

The Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee will meet on Jan. 20 to discuss the compound and the study's findings.

Like Pittsburgh imaging compound B (PiB), florbetapir binds to beta-amyloid plaques in the living brain.

PiB's use, however, has been limited by its short half-life of 20 minutes.

Florbetapir achieves maximum uptake at 30 minutes and remains unchanged for the next 60 minutes, “providing a wide time window to obtain a 10-minute image,” the authors noted.

The prospective study involved 35 patients in hospice or long-term care facilities who were expected to die within 6 months.

Six of the patients were used to validate the imaging procedure while the remaining 29 were used in the primary validation study.

Among the 29 in the validation analysis, the mean age was 80 years.

This group included 13 with a clinical diagnosis of Alzheimer's, 5 with other dementias, 9 with normal cognition, and the rest with mild cognitive impairment.

Their mean Mini-Mental State Examination (MMSE) score was 3.8.

The control group comprised 74 young, healthy subjects, 27 of whom were positive for the APOE e4 allele, which greatly increases the risk of developing Alzheimer's in later life.

The control subjects had a mean age of 27 years and a mean MMSE score of 29.7.

Florbetapir imaging was negative for all 74 subjects, including those with the APOE e4 allele.

Florbetapir-PET imaging in the 35 patients was significantly correlated with both immunohistochemistry and silver stain for beta-amyloid plaques in each of the six brain regions that the investigators examined (frontal, temporal, parietal, anterior and posterior cingulate, precuneus, and cerebellum).

At autopsy, 15 patients in the validation group met pathologic criteria for Alzheimer's disease.

Of these, 14 had positive florbetapir-PET scans, leading to a sensitivity of 93%.

The other 14 patients had low levels of beta-amyloid plaque on autopsy, and did not meet the diagnostic criteria for Alzheimer's.

All 14 also had negative florbetapir-PET scans, giving 100% specificity.

“The neuropathological diagnosis in the participants who did not meet pathological criteria for AD included dementia with Lewy bodies, hippocampal sclerosis, Parkinson's disease, subcortical microscopic infarct, mesial temporal lobe neurofibrillary tangles, neurofibrillary tangles with argyrophilic grains and glial tauopathy, and no neuropathology,” the authors wrote.

Of the 15 patients in the validation cohort who had a clinical diagnosis of dementia during life, 3 did not have the same diagnosis on autopsy.

One of these patients had a clinical diagnosis of probable Alzheimer's but did not have it on autopsy, whereas one with a clinical diagnosis of Parkinson's disease dementia and one with a clinical diagnosis of Lewy body dementia actually had Alzheimer's.

Florbetapir-PET correctly predicted the presence or absence of Alzheimer's disease in these patients.

The authors noted that the patient sample used in the study did not represent a typical clinical population, most of whom would be referred for initial signs of cognitive impairment.

Rather, the cohort was selected “for their unique ability to provide information about the ability of florbetapir-PET imaging to accurately identify and quantify beta-amyloid with the shortest interval between imaging and definitive pathological evaluation possible,” they said.

The study was funded primarily by Avid Radiopharmaceuticals. Dr. Clark and eight of the coauthors are stockholders and/or employees of the company. All of the other coauthors received research grants, and most are educators, paid investigators, or members of the speakers bureau for Avid or for Eli Lilly, which acquired the company last November.

Positron-emission tomography in combination with the radiolabeled compound florbetapir F-18 detected beta-amyloid plaques with 93% sensitivity and 100% specificity in the brains of 35 elderly patients, most of whom had some form of dementia.

Lead investigator Dr. Christopher Clark and his colleagues wrote that florbetapir-PET imaging could be an important diagnostic tool for Alzheimer's disease – perhaps with the ability to detect brain plaques early in a prodromal stage of the disease – and to measure plaque changes in relation to therapeutic response in future drug studies, according to Dr. Clark, medical director of Avid Radiopharmaceuticals, the company testing the compound (JAMA 2011;305:275-83).

The study also represents the first time an amyloid imaging agent has been tested against autopsy results, said coinvestigator Dr. Marwan N. Sabbagh, founding director of the Cleo Roberts Center for Clinical Research in Sun City, Ariz.

“It's really exciting to be able to correlate imaging so strongly with autopsy findings,” Dr. Sabbagh said.

But Dr. Clark and his coinvestigators cautioned that the study does not make it clear what specific clinical applications the imaging procedure could have, be it the clinical diagnosis of Alzheimer's disease or the prediction of progression to dementia.

The Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee will meet on Jan. 20 to discuss the compound and the study's findings.

Like Pittsburgh imaging compound B (PiB), florbetapir binds to beta-amyloid plaques in the living brain.

PiB's use, however, has been limited by its short half-life of 20 minutes.

Florbetapir achieves maximum uptake at 30 minutes and remains unchanged for the next 60 minutes, “providing a wide time window to obtain a 10-minute image,” the authors noted.

The prospective study involved 35 patients in hospice or long-term care facilities who were expected to die within 6 months.

Six of the patients were used to validate the imaging procedure while the remaining 29 were used in the primary validation study.

Among the 29 in the validation analysis, the mean age was 80 years.

This group included 13 with a clinical diagnosis of Alzheimer's, 5 with other dementias, 9 with normal cognition, and the rest with mild cognitive impairment.

Their mean Mini-Mental State Examination (MMSE) score was 3.8.

The control group comprised 74 young, healthy subjects, 27 of whom were positive for the APOE e4 allele, which greatly increases the risk of developing Alzheimer's in later life.

The control subjects had a mean age of 27 years and a mean MMSE score of 29.7.

Florbetapir imaging was negative for all 74 subjects, including those with the APOE e4 allele.

Florbetapir-PET imaging in the 35 patients was significantly correlated with both immunohistochemistry and silver stain for beta-amyloid plaques in each of the six brain regions that the investigators examined (frontal, temporal, parietal, anterior and posterior cingulate, precuneus, and cerebellum).

At autopsy, 15 patients in the validation group met pathologic criteria for Alzheimer's disease.

Of these, 14 had positive florbetapir-PET scans, leading to a sensitivity of 93%.

The other 14 patients had low levels of beta-amyloid plaque on autopsy, and did not meet the diagnostic criteria for Alzheimer's.

All 14 also had negative florbetapir-PET scans, giving 100% specificity.

“The neuropathological diagnosis in the participants who did not meet pathological criteria for AD included dementia with Lewy bodies, hippocampal sclerosis, Parkinson's disease, subcortical microscopic infarct, mesial temporal lobe neurofibrillary tangles, neurofibrillary tangles with argyrophilic grains and glial tauopathy, and no neuropathology,” the authors wrote.

Of the 15 patients in the validation cohort who had a clinical diagnosis of dementia during life, 3 did not have the same diagnosis on autopsy.

One of these patients had a clinical diagnosis of probable Alzheimer's but did not have it on autopsy, whereas one with a clinical diagnosis of Parkinson's disease dementia and one with a clinical diagnosis of Lewy body dementia actually had Alzheimer's.

Florbetapir-PET correctly predicted the presence or absence of Alzheimer's disease in these patients.

The authors noted that the patient sample used in the study did not represent a typical clinical population, most of whom would be referred for initial signs of cognitive impairment.

Rather, the cohort was selected “for their unique ability to provide information about the ability of florbetapir-PET imaging to accurately identify and quantify beta-amyloid with the shortest interval between imaging and definitive pathological evaluation possible,” they said.

The study was funded primarily by Avid Radiopharmaceuticals. Dr. Clark and eight of the coauthors are stockholders and/or employees of the company. All of the other coauthors received research grants, and most are educators, paid investigators, or members of the speakers bureau for Avid or for Eli Lilly, which acquired the company last November.

Major Finding: Bariatric surgery normalized blood glucose and insulin in Hispanic and black patients over a 3-year period.

Data Source: A review of 1,603 patients found that the 47% with elevated blood glucose and insulin had complete resolution of those abnormalities by 1 year and normal levels over a 3-year follow-up.

Disclosures: Dr. Livingstone had no financial disclosures. Dr. Nestor F. De La Cruz-Munoz Jr., a coauthor, is a consultant and proctor for Ethicon.

PALM BEACH, FLA. – Bariatric surgery resulted in the complete remission of type 2 diabetes and prediabetes in a group of mostly Hispanic and black patients.

Within 1 year of surgery, 100% of the patients with those disorders experienced a normalization of fasting blood glucose and hemoglobin A_1c, and they lost a mean of 40 kg, Dr. Alan Livingstone said at the meeting.

By the end of the 3-year follow-up period, all patients still had normal levels of blood glucose and insulin.

“Uncontrolled type 2 diabetes is highly prevalent among ethnic minorities,” said Dr. Livingstone, the Lucille and DeWitt Daughtry Professor and Chairman of Surgery at the University of Miami Miller School of Medicine and chief of surgery at Jackson Memorial Hospital, Miami. “Bariatric surgery helps to effectively treat these diverse minority groups and is a safe and effective option for permanent weight loss and chronic disease risk improvement in this population.”

He reported on a cohort of 1,603 adult bariatric surgery patients, of whom 66% were Hispanic, 17% were black, and the rest were other ethnicities. They were prospectively entered into a research database and then retrospectively studied.

“Minorities are at a particularly high risk for type 2 diabetes and its associated complications,” Dr. Livingstone said. “While only 6% of whites have [the disorder], it's present in 10% of Hispanics and 12% of blacks – a huge burden of disease.”

The patients' mean age was 45 years; most (77%) were female. The mean preoperative weight was 130 kg; the mean body mass index, 47 kg/m

Most of the group already had some insulin abnormality; 377 had diagnosed type 2 diabetes, 107 had undiagnosed type 2 (fasting blood glucose of more than 126 mg/dL), and 276 had prediabetes (fasting blood glucose of 100-125 mg/dL). Among those with elevated blood glucose, the mean HbA_1c was 8%. The rest of the group had a normal insulin profile.

Most patients underwent gastric bypass (90%); the rest had gastric banding. “The amount of weight loss was profound in the first year, as expected,” Dr. Livingstone said.

There was no significant difference in weight loss between the diagnostic groups. Body mass index also fell quickly, correlating with weight loss. By the end of the first 6 months, the mean BMI had dropped to 35 kg/m

Fasting blood glucose and HbA_1c also improved rapidly and significantly in all those with preoperatively elevated levels. “It's important to note how quickly this happened,” Dr. Livingstone said. “Within the first year, all of these patients had normal fasting blood glucose and an HbA_1c of 6% or below.” Again, these values remained steady and in the normal range in the entire 3-year follow-up cohort. “This is a tremendous accomplishment,” he said.

However, Dr. Bruce Schirmer of the University of Virginia, Charlottesville, cautioned that a 3-year follow-up period may not be long enough to proclaim bariatric surgery as a cure for type 2 diabetes in any population.

“In mostly Caucasian populations, if you follow the patients for up to 5 years, you see that 15%-20%, at least, have some weight regain and with it, a return to diabetes. So to make this statement that there is no weight regain and no return to the disorder is a little premature,” Dr. Schirmer said.

Major Finding: Bariatric surgery normalized blood glucose and insulin in Hispanic and black patients over a 3-year period.

Data Source: A review of 1,603 patients found that the 47% with elevated blood glucose and insulin had complete resolution of those abnormalities by 1 year and normal levels over a 3-year follow-up.

Disclosures: Dr. Livingstone had no financial disclosures. Dr. Nestor F. De La Cruz-Munoz Jr., a coauthor, is a consultant and proctor for Ethicon.

PALM BEACH, FLA. – Bariatric surgery resulted in the complete remission of type 2 diabetes and prediabetes in a group of mostly Hispanic and black patients.

Within 1 year of surgery, 100% of the patients with those disorders experienced a normalization of fasting blood glucose and hemoglobin A_1c, and they lost a mean of 40 kg, Dr. Alan Livingstone said at the meeting.

By the end of the 3-year follow-up period, all patients still had normal levels of blood glucose and insulin.

“Uncontrolled type 2 diabetes is highly prevalent among ethnic minorities,” said Dr. Livingstone, the Lucille and DeWitt Daughtry Professor and Chairman of Surgery at the University of Miami Miller School of Medicine and chief of surgery at Jackson Memorial Hospital, Miami. “Bariatric surgery helps to effectively treat these diverse minority groups and is a safe and effective option for permanent weight loss and chronic disease risk improvement in this population.”

He reported on a cohort of 1,603 adult bariatric surgery patients, of whom 66% were Hispanic, 17% were black, and the rest were other ethnicities. They were prospectively entered into a research database and then retrospectively studied.

“Minorities are at a particularly high risk for type 2 diabetes and its associated complications,” Dr. Livingstone said. “While only 6% of whites have [the disorder], it's present in 10% of Hispanics and 12% of blacks – a huge burden of disease.”

The patients' mean age was 45 years; most (77%) were female. The mean preoperative weight was 130 kg; the mean body mass index, 47 kg/m

Most of the group already had some insulin abnormality; 377 had diagnosed type 2 diabetes, 107 had undiagnosed type 2 (fasting blood glucose of more than 126 mg/dL), and 276 had prediabetes (fasting blood glucose of 100-125 mg/dL). Among those with elevated blood glucose, the mean HbA_1c was 8%. The rest of the group had a normal insulin profile.

Most patients underwent gastric bypass (90%); the rest had gastric banding. “The amount of weight loss was profound in the first year, as expected,” Dr. Livingstone said.

There was no significant difference in weight loss between the diagnostic groups. Body mass index also fell quickly, correlating with weight loss. By the end of the first 6 months, the mean BMI had dropped to 35 kg/m

Fasting blood glucose and HbA_1c also improved rapidly and significantly in all those with preoperatively elevated levels. “It's important to note how quickly this happened,” Dr. Livingstone said. “Within the first year, all of these patients had normal fasting blood glucose and an HbA_1c of 6% or below.” Again, these values remained steady and in the normal range in the entire 3-year follow-up cohort. “This is a tremendous accomplishment,” he said.

However, Dr. Bruce Schirmer of the University of Virginia, Charlottesville, cautioned that a 3-year follow-up period may not be long enough to proclaim bariatric surgery as a cure for type 2 diabetes in any population.

“In mostly Caucasian populations, if you follow the patients for up to 5 years, you see that 15%-20%, at least, have some weight regain and with it, a return to diabetes. So to make this statement that there is no weight regain and no return to the disorder is a little premature,” Dr. Schirmer said.

Major Finding: Bariatric surgery normalized blood glucose and insulin in Hispanic and black patients over a 3-year period.

Data Source: A review of 1,603 patients found that the 47% with elevated blood glucose and insulin had complete resolution of those abnormalities by 1 year and normal levels over a 3-year follow-up.

Disclosures: Dr. Livingstone had no financial disclosures. Dr. Nestor F. De La Cruz-Munoz Jr., a coauthor, is a consultant and proctor for Ethicon.

PALM BEACH, FLA. – Bariatric surgery resulted in the complete remission of type 2 diabetes and prediabetes in a group of mostly Hispanic and black patients.

Within 1 year of surgery, 100% of the patients with those disorders experienced a normalization of fasting blood glucose and hemoglobin A_1c, and they lost a mean of 40 kg, Dr. Alan Livingstone said at the meeting.

By the end of the 3-year follow-up period, all patients still had normal levels of blood glucose and insulin.

“Uncontrolled type 2 diabetes is highly prevalent among ethnic minorities,” said Dr. Livingstone, the Lucille and DeWitt Daughtry Professor and Chairman of Surgery at the University of Miami Miller School of Medicine and chief of surgery at Jackson Memorial Hospital, Miami. “Bariatric surgery helps to effectively treat these diverse minority groups and is a safe and effective option for permanent weight loss and chronic disease risk improvement in this population.”

He reported on a cohort of 1,603 adult bariatric surgery patients, of whom 66% were Hispanic, 17% were black, and the rest were other ethnicities. They were prospectively entered into a research database and then retrospectively studied.

“Minorities are at a particularly high risk for type 2 diabetes and its associated complications,” Dr. Livingstone said. “While only 6% of whites have [the disorder], it's present in 10% of Hispanics and 12% of blacks – a huge burden of disease.”

The patients' mean age was 45 years; most (77%) were female. The mean preoperative weight was 130 kg; the mean body mass index, 47 kg/m

Most of the group already had some insulin abnormality; 377 had diagnosed type 2 diabetes, 107 had undiagnosed type 2 (fasting blood glucose of more than 126 mg/dL), and 276 had prediabetes (fasting blood glucose of 100-125 mg/dL). Among those with elevated blood glucose, the mean HbA_1c was 8%. The rest of the group had a normal insulin profile.

Most patients underwent gastric bypass (90%); the rest had gastric banding. “The amount of weight loss was profound in the first year, as expected,” Dr. Livingstone said.

There was no significant difference in weight loss between the diagnostic groups. Body mass index also fell quickly, correlating with weight loss. By the end of the first 6 months, the mean BMI had dropped to 35 kg/m

Fasting blood glucose and HbA_1c also improved rapidly and significantly in all those with preoperatively elevated levels. “It's important to note how quickly this happened,” Dr. Livingstone said. “Within the first year, all of these patients had normal fasting blood glucose and an HbA_1c of 6% or below.” Again, these values remained steady and in the normal range in the entire 3-year follow-up cohort. “This is a tremendous accomplishment,” he said.

However, Dr. Bruce Schirmer of the University of Virginia, Charlottesville, cautioned that a 3-year follow-up period may not be long enough to proclaim bariatric surgery as a cure for type 2 diabetes in any population.

“In mostly Caucasian populations, if you follow the patients for up to 5 years, you see that 15%-20%, at least, have some weight regain and with it, a return to diabetes. So to make this statement that there is no weight regain and no return to the disorder is a little premature,” Dr. Schirmer said.

Major Finding: In 41% of patients, rifaximin was associated with adequate relief of global IBS symptoms during the first 4 weeks after treatment ended, compared with 32% who took placebo (P less than .001), in two studies combined.

Data Source: Two phase III, double-blind placebo-controlled studies of a 2-week course of rifaximin at a dose of 550 mg three times daily; a total of 1,260 patients were randomized.

Disclosures: Salix Pharmaceuticals sponsored both studies. All of the paper's authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers' fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of the primary investigator, holds patents licensed by Salix Pharmaceuticals.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote (N. Eng. J. Med. 2011;364:22-32).

TARGET 1 found that 41% of patients who were taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, which is a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, “some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms.”

Both studies were funded by Salix Pharmaceuticals, the drug's manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients' average age was 46 years in each group. Overall, most of the patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with “yes” or “no.” Dr. Pimentel and his associates prospectively determined the threshold of “adequate relief” as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001), the investigators said.

For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, “more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies,” the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

Dr. Pimentel and his associates provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

“Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota,” they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin's effect and the relatively small difference between the active and placebo responses.

“The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant,” he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies' positive findings, including the favorable safety profile, he wrote that “clinicians should proceed with caution.”

Although “rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS,” he also wrote that, “taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account.”

Until researchers are able to identify a subgroup of patients that might respond well to the drug, “It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies,” he wrote.

Dr. Tack reported no financial relationship with Salix.

Major Finding: In 41% of patients, rifaximin was associated with adequate relief of global IBS symptoms during the first 4 weeks after treatment ended, compared with 32% who took placebo (P less than .001), in two studies combined.

Data Source: Two phase III, double-blind placebo-controlled studies of a 2-week course of rifaximin at a dose of 550 mg three times daily; a total of 1,260 patients were randomized.

Disclosures: Salix Pharmaceuticals sponsored both studies. All of the paper's authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers' fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of the primary investigator, holds patents licensed by Salix Pharmaceuticals.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote (N. Eng. J. Med. 2011;364:22-32).

TARGET 1 found that 41% of patients who were taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, which is a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, “some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms.”

Both studies were funded by Salix Pharmaceuticals, the drug's manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients' average age was 46 years in each group. Overall, most of the patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with “yes” or “no.” Dr. Pimentel and his associates prospectively determined the threshold of “adequate relief” as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001), the investigators said.

For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, “more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies,” the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

Dr. Pimentel and his associates provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

“Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota,” they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin's effect and the relatively small difference between the active and placebo responses.

“The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant,” he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies' positive findings, including the favorable safety profile, he wrote that “clinicians should proceed with caution.”

Although “rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS,” he also wrote that, “taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account.”

Until researchers are able to identify a subgroup of patients that might respond well to the drug, “It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies,” he wrote.

Dr. Tack reported no financial relationship with Salix.

Major Finding: In 41% of patients, rifaximin was associated with adequate relief of global IBS symptoms during the first 4 weeks after treatment ended, compared with 32% who took placebo (P less than .001), in two studies combined.

Data Source: Two phase III, double-blind placebo-controlled studies of a 2-week course of rifaximin at a dose of 550 mg three times daily; a total of 1,260 patients were randomized.

Disclosures: Salix Pharmaceuticals sponsored both studies. All of the paper's authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers' fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of the primary investigator, holds patents licensed by Salix Pharmaceuticals.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote (N. Eng. J. Med. 2011;364:22-32).

TARGET 1 found that 41% of patients who were taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, which is a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, “some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms.”

Both studies were funded by Salix Pharmaceuticals, the drug's manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients' average age was 46 years in each group. Overall, most of the patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with “yes” or “no.” Dr. Pimentel and his associates prospectively determined the threshold of “adequate relief” as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001), the investigators said.

For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, “more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies,” the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

Dr. Pimentel and his associates provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

“Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota,” they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin's effect and the relatively small difference between the active and placebo responses.

“The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant,” he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies' positive findings, including the favorable safety profile, he wrote that “clinicians should proceed with caution.”

Although “rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS,” he also wrote that, “taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account.”

Until researchers are able to identify a subgroup of patients that might respond well to the drug, “It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies,” he wrote.

Dr. Tack reported no financial relationship with Salix.

The Affordable Care Act, which became law this January, stipulates that clinicians must assess patients aged 65 years or older for cognitive impairment as part of their annual wellness visit.

But the U.S. Preventive Services Task Force has never endorsed a screening tool for cognitive decline, noting that no data consistently support one of the many existing tools over another.

So, what's a busy primary care physician to do? Some researchers – including Dr. James Galvin of Washington University, St. Louis – think a screening tool called the AD8 could be one answer.

Dr. Galvin created the screening tool along with colleagues at the university's Alzheimer's Disease Research Center. During a Webinar sponsored by the Alzheimer Research Forum, he presented data showing that AD8 is fast, easy, inexpensive, and very accurate in identifying patients who are beginning to show early signs of cognitive decline.

In an unselected population, the tool has a sensitivity of more than 84% and specificity of more than 80%, although both measures were much higher in the dementia clinic where it was piloted. Overall, the AD8 has proved more useful than the Mini Mental State Examination in picking out patients with the very earliest signs of cognitive impairment, Dr. Galvin said during the Webinar (Arch. Neurol. 2007;64:718-24).

The eight-question survey asks an informant whether the patient has experienced any changes in executive function or memory over the past few years.

“It's brief, inexpensive, easy to give and score, reliable, socially acceptable, and culturally sensitive,” Dr. Galvin said.

Because it provides a picture of change related to baseline, the AD8 avoids the problem of a “snapshot” test, which could, for example, falsely identify cognitive problems in someone who has never had a good memory. Because the AD8 does not test patients on acquired learning, it is not educationally biased. The test also is culturally neutral because it focuses on changes in basic activities in which everyone engages.

Most screening tests “share performance-based problems,” he said. “They might be insensitive to very early dementia, have a cultural or educational bias, or be heavily weighted toward memory impairment or another single cognitive domain. And unless they are done serially, you really have no idea where the patient was before [the test], and no sense of whether the findings interfere with their occupation or social function.”

The AD8 asks informants to answer yes, no, or don't know to whether the patient has changed in eight areas: problems with daily judgment and decision making; decreased interest in hobbies or activities; repeating things over and over; trouble learning how to use a new tool or appliance; forgetting the month or year; trouble with financial affairs; trouble recalling appointments; and daily problems with thinking and memory.

A score of two or more “yes” answers is a positive screen, indicating that cognitive impairment is likely. Positive screening results also strongly correlate with the new Alzheimer's disease biomarker diagnostic standards.

Patients with a positive AD8 are significantly more likely to have brain atrophy in the temporal lobe, hippocampus, and parahippocampal gyrus than are those with a negative screen. Patients with a positive screen also are more likely to have beta amyloid₄₂ brain plaques, to have decreased beta amyloid₄₂, increased tau, and abnormal beta amyloid/tau ratios in cerebrospinal fluid (Brain 2010;133:3290-300).

However, the test is not a method of diagnosing any particular cognitive disorder – even mild cognitive impairment, Dr. Galvin said. A positive AD8 will most likely mean additional tests for the patient, including brain imaging, biomarkers, neuropsychological testing, and other diagnostic activities.

Validation studies of the AD8 have confirmed that it can identify early changes in a plethora of dementias, including Alzheimer's disease and progressive aphasias, as well as Lewy body, frontotemporal, and vascular dementia. Therefore, early identification is its biggest advantage, he said.

“As new disease-modifying medications are developed, those at the earliest stages of their disease will probably get the biggest benefit,” Dr. Galvin said. An earlier diagnosis not only affords the opportunity to benefit from new drugs, when they become available, but also allows families and patients to work together to plan the future, while the patient is still able to make meaningful contributions.

AD8's future is by no means ensured. The tool is available online, free to any clinician who wants to download it. But whether primary care doctors will use it – and whether patients will want it – is another matter, said Dr. Galvin and Dr. Tracey Holsinger of Duke University and the Durham (N.C.) Veterans Affairs Medical Center.

Conflicting directives from the federal government and the USPSTF might make clinicians cringe when faced with the cognitive-screening mandate, Dr. Galvin said. “There is just no clear plan about how best to screen and what instrument to use. … Dementia screening simply has not been a routine part of primary care practice,” and certainly not for a nontargeted population that begins at a relatively low-risk age for age-related dementias. “Targeted screening makes a lot more sense, and it's my belief that large population screening will yield very few cases.” However, he said, this is the hand that politicians have dealt primary care, “unless the Task Force can be persuaded to review its recommendations and make new ones based on the current data.”

Even if physicians quail at the thought of having one more box to tick off in an annual exam, patients will probably like the security an annual cognitive screen can provide, Dr. Holsinger said. She and her colleagues recently conducted a survey of 345 primary care patients at the Durham VA Medical Center. After discussing the risks and benefits of a cognitive screen that could identify early dementia, the subjects were asked whether they would want to know of their probable diagnosis. “Eighty-one percent said they would want to know,” she said.

Factors associated with the desire for screening were acceptance of other screening tests (depression, breast, and prostate cancer; odds ratio 3.7), male gender (OR 3.2), and the belief that effective treatment for dementia exists (OR 2) (Int. J. Geriatr. Psych. 2010 [doi:10.1002/gps.2536]).

The AD8 sounds good on the surface, but how it will fit into a busy primary care day is still unclear, said Dr. Eric Tangalos, an internist at the Mayo Clinic, Rochester, Minn. Having an informant fill out the paper might throw some bias into the pot at the very beginning of the process, he said during the webinar. “In my practice, if a 65-year-old shows up for an annual wellness exam with a spouse, that sends my red flags flying. We need to be very cautious about applying an instrument [that was tested in dementia clinics] to a broad population that is not at a high-risk age.”

Primary care physicians already are ultracautious about entering the dementia arena, he said. “We already know primary care docs do not want to open Pandora's box, even when the disease is confronting them. We're saying 'Run toward that diagnosis, rather than run away from it.'”

Dr. Galvin agreed, but reminded the panel that the die has been cast. “There is not a lot of evidence that anyone needs to be seen annually for something like this – this is really a political approach to health care that is quite a bit different from anything the USPSTF policy has recommended. But even though we're not exactly sure how it will all play out, it's going to be up to the practices to get it done.”

None of the panel members expressed any financial conflicts related to the screening tool.

The Affordable Care Act, which became law this January, stipulates that clinicians must assess patients aged 65 years or older for cognitive impairment as part of their annual wellness visit.

But the U.S. Preventive Services Task Force has never endorsed a screening tool for cognitive decline, noting that no data consistently support one of the many existing tools over another.

So, what's a busy primary care physician to do? Some researchers – including Dr. James Galvin of Washington University, St. Louis – think a screening tool called the AD8 could be one answer.

Dr. Galvin created the screening tool along with colleagues at the university's Alzheimer's Disease Research Center. During a Webinar sponsored by the Alzheimer Research Forum, he presented data showing that AD8 is fast, easy, inexpensive, and very accurate in identifying patients who are beginning to show early signs of cognitive decline.

In an unselected population, the tool has a sensitivity of more than 84% and specificity of more than 80%, although both measures were much higher in the dementia clinic where it was piloted. Overall, the AD8 has proved more useful than the Mini Mental State Examination in picking out patients with the very earliest signs of cognitive impairment, Dr. Galvin said during the Webinar (Arch. Neurol. 2007;64:718-24).

The eight-question survey asks an informant whether the patient has experienced any changes in executive function or memory over the past few years.

“It's brief, inexpensive, easy to give and score, reliable, socially acceptable, and culturally sensitive,” Dr. Galvin said.

Because it provides a picture of change related to baseline, the AD8 avoids the problem of a “snapshot” test, which could, for example, falsely identify cognitive problems in someone who has never had a good memory. Because the AD8 does not test patients on acquired learning, it is not educationally biased. The test also is culturally neutral because it focuses on changes in basic activities in which everyone engages.

Most screening tests “share performance-based problems,” he said. “They might be insensitive to very early dementia, have a cultural or educational bias, or be heavily weighted toward memory impairment or another single cognitive domain. And unless they are done serially, you really have no idea where the patient was before [the test], and no sense of whether the findings interfere with their occupation or social function.”

The AD8 asks informants to answer yes, no, or don't know to whether the patient has changed in eight areas: problems with daily judgment and decision making; decreased interest in hobbies or activities; repeating things over and over; trouble learning how to use a new tool or appliance; forgetting the month or year; trouble with financial affairs; trouble recalling appointments; and daily problems with thinking and memory.

A score of two or more “yes” answers is a positive screen, indicating that cognitive impairment is likely. Positive screening results also strongly correlate with the new Alzheimer's disease biomarker diagnostic standards.

Patients with a positive AD8 are significantly more likely to have brain atrophy in the temporal lobe, hippocampus, and parahippocampal gyrus than are those with a negative screen. Patients with a positive screen also are more likely to have beta amyloid₄₂ brain plaques, to have decreased beta amyloid₄₂, increased tau, and abnormal beta amyloid/tau ratios in cerebrospinal fluid (Brain 2010;133:3290-300).

However, the test is not a method of diagnosing any particular cognitive disorder – even mild cognitive impairment, Dr. Galvin said. A positive AD8 will most likely mean additional tests for the patient, including brain imaging, biomarkers, neuropsychological testing, and other diagnostic activities.

Validation studies of the AD8 have confirmed that it can identify early changes in a plethora of dementias, including Alzheimer's disease and progressive aphasias, as well as Lewy body, frontotemporal, and vascular dementia. Therefore, early identification is its biggest advantage, he said.

“As new disease-modifying medications are developed, those at the earliest stages of their disease will probably get the biggest benefit,” Dr. Galvin said. An earlier diagnosis not only affords the opportunity to benefit from new drugs, when they become available, but also allows families and patients to work together to plan the future, while the patient is still able to make meaningful contributions.

AD8's future is by no means ensured. The tool is available online, free to any clinician who wants to download it. But whether primary care doctors will use it – and whether patients will want it – is another matter, said Dr. Galvin and Dr. Tracey Holsinger of Duke University and the Durham (N.C.) Veterans Affairs Medical Center.

Conflicting directives from the federal government and the USPSTF might make clinicians cringe when faced with the cognitive-screening mandate, Dr. Galvin said. “There is just no clear plan about how best to screen and what instrument to use. … Dementia screening simply has not been a routine part of primary care practice,” and certainly not for a nontargeted population that begins at a relatively low-risk age for age-related dementias. “Targeted screening makes a lot more sense, and it's my belief that large population screening will yield very few cases.” However, he said, this is the hand that politicians have dealt primary care, “unless the Task Force can be persuaded to review its recommendations and make new ones based on the current data.”

Even if physicians quail at the thought of having one more box to tick off in an annual exam, patients will probably like the security an annual cognitive screen can provide, Dr. Holsinger said. She and her colleagues recently conducted a survey of 345 primary care patients at the Durham VA Medical Center. After discussing the risks and benefits of a cognitive screen that could identify early dementia, the subjects were asked whether they would want to know of their probable diagnosis. “Eighty-one percent said they would want to know,” she said.

Factors associated with the desire for screening were acceptance of other screening tests (depression, breast, and prostate cancer; odds ratio 3.7), male gender (OR 3.2), and the belief that effective treatment for dementia exists (OR 2) (Int. J. Geriatr. Psych. 2010 [doi:10.1002/gps.2536]).

The AD8 sounds good on the surface, but how it will fit into a busy primary care day is still unclear, said Dr. Eric Tangalos, an internist at the Mayo Clinic, Rochester, Minn. Having an informant fill out the paper might throw some bias into the pot at the very beginning of the process, he said during the webinar. “In my practice, if a 65-year-old shows up for an annual wellness exam with a spouse, that sends my red flags flying. We need to be very cautious about applying an instrument [that was tested in dementia clinics] to a broad population that is not at a high-risk age.”

Primary care physicians already are ultracautious about entering the dementia arena, he said. “We already know primary care docs do not want to open Pandora's box, even when the disease is confronting them. We're saying 'Run toward that diagnosis, rather than run away from it.'”

Dr. Galvin agreed, but reminded the panel that the die has been cast. “There is not a lot of evidence that anyone needs to be seen annually for something like this – this is really a political approach to health care that is quite a bit different from anything the USPSTF policy has recommended. But even though we're not exactly sure how it will all play out, it's going to be up to the practices to get it done.”

None of the panel members expressed any financial conflicts related to the screening tool.

The Affordable Care Act, which became law this January, stipulates that clinicians must assess patients aged 65 years or older for cognitive impairment as part of their annual wellness visit.

But the U.S. Preventive Services Task Force has never endorsed a screening tool for cognitive decline, noting that no data consistently support one of the many existing tools over another.

So, what's a busy primary care physician to do? Some researchers – including Dr. James Galvin of Washington University, St. Louis – think a screening tool called the AD8 could be one answer.

Dr. Galvin created the screening tool along with colleagues at the university's Alzheimer's Disease Research Center. During a Webinar sponsored by the Alzheimer Research Forum, he presented data showing that AD8 is fast, easy, inexpensive, and very accurate in identifying patients who are beginning to show early signs of cognitive decline.

In an unselected population, the tool has a sensitivity of more than 84% and specificity of more than 80%, although both measures were much higher in the dementia clinic where it was piloted. Overall, the AD8 has proved more useful than the Mini Mental State Examination in picking out patients with the very earliest signs of cognitive impairment, Dr. Galvin said during the Webinar (Arch. Neurol. 2007;64:718-24).

The eight-question survey asks an informant whether the patient has experienced any changes in executive function or memory over the past few years.

“It's brief, inexpensive, easy to give and score, reliable, socially acceptable, and culturally sensitive,” Dr. Galvin said.

Because it provides a picture of change related to baseline, the AD8 avoids the problem of a “snapshot” test, which could, for example, falsely identify cognitive problems in someone who has never had a good memory. Because the AD8 does not test patients on acquired learning, it is not educationally biased. The test also is culturally neutral because it focuses on changes in basic activities in which everyone engages.

Most screening tests “share performance-based problems,” he said. “They might be insensitive to very early dementia, have a cultural or educational bias, or be heavily weighted toward memory impairment or another single cognitive domain. And unless they are done serially, you really have no idea where the patient was before [the test], and no sense of whether the findings interfere with their occupation or social function.”

The AD8 asks informants to answer yes, no, or don't know to whether the patient has changed in eight areas: problems with daily judgment and decision making; decreased interest in hobbies or activities; repeating things over and over; trouble learning how to use a new tool or appliance; forgetting the month or year; trouble with financial affairs; trouble recalling appointments; and daily problems with thinking and memory.

A score of two or more “yes” answers is a positive screen, indicating that cognitive impairment is likely. Positive screening results also strongly correlate with the new Alzheimer's disease biomarker diagnostic standards.

Patients with a positive AD8 are significantly more likely to have brain atrophy in the temporal lobe, hippocampus, and parahippocampal gyrus than are those with a negative screen. Patients with a positive screen also are more likely to have beta amyloid₄₂ brain plaques, to have decreased beta amyloid₄₂, increased tau, and abnormal beta amyloid/tau ratios in cerebrospinal fluid (Brain 2010;133:3290-300).

However, the test is not a method of diagnosing any particular cognitive disorder – even mild cognitive impairment, Dr. Galvin said. A positive AD8 will most likely mean additional tests for the patient, including brain imaging, biomarkers, neuropsychological testing, and other diagnostic activities.

Validation studies of the AD8 have confirmed that it can identify early changes in a plethora of dementias, including Alzheimer's disease and progressive aphasias, as well as Lewy body, frontotemporal, and vascular dementia. Therefore, early identification is its biggest advantage, he said.

“As new disease-modifying medications are developed, those at the earliest stages of their disease will probably get the biggest benefit,” Dr. Galvin said. An earlier diagnosis not only affords the opportunity to benefit from new drugs, when they become available, but also allows families and patients to work together to plan the future, while the patient is still able to make meaningful contributions.

AD8's future is by no means ensured. The tool is available online, free to any clinician who wants to download it. But whether primary care doctors will use it – and whether patients will want it – is another matter, said Dr. Galvin and Dr. Tracey Holsinger of Duke University and the Durham (N.C.) Veterans Affairs Medical Center.

Conflicting directives from the federal government and the USPSTF might make clinicians cringe when faced with the cognitive-screening mandate, Dr. Galvin said. “There is just no clear plan about how best to screen and what instrument to use. … Dementia screening simply has not been a routine part of primary care practice,” and certainly not for a nontargeted population that begins at a relatively low-risk age for age-related dementias. “Targeted screening makes a lot more sense, and it's my belief that large population screening will yield very few cases.” However, he said, this is the hand that politicians have dealt primary care, “unless the Task Force can be persuaded to review its recommendations and make new ones based on the current data.”

Even if physicians quail at the thought of having one more box to tick off in an annual exam, patients will probably like the security an annual cognitive screen can provide, Dr. Holsinger said. She and her colleagues recently conducted a survey of 345 primary care patients at the Durham VA Medical Center. After discussing the risks and benefits of a cognitive screen that could identify early dementia, the subjects were asked whether they would want to know of their probable diagnosis. “Eighty-one percent said they would want to know,” she said.

Factors associated with the desire for screening were acceptance of other screening tests (depression, breast, and prostate cancer; odds ratio 3.7), male gender (OR 3.2), and the belief that effective treatment for dementia exists (OR 2) (Int. J. Geriatr. Psych. 2010 [doi:10.1002/gps.2536]).

The AD8 sounds good on the surface, but how it will fit into a busy primary care day is still unclear, said Dr. Eric Tangalos, an internist at the Mayo Clinic, Rochester, Minn. Having an informant fill out the paper might throw some bias into the pot at the very beginning of the process, he said during the webinar. “In my practice, if a 65-year-old shows up for an annual wellness exam with a spouse, that sends my red flags flying. We need to be very cautious about applying an instrument [that was tested in dementia clinics] to a broad population that is not at a high-risk age.”

Primary care physicians already are ultracautious about entering the dementia arena, he said. “We already know primary care docs do not want to open Pandora's box, even when the disease is confronting them. We're saying 'Run toward that diagnosis, rather than run away from it.'”

Dr. Galvin agreed, but reminded the panel that the die has been cast. “There is not a lot of evidence that anyone needs to be seen annually for something like this – this is really a political approach to health care that is quite a bit different from anything the USPSTF policy has recommended. But even though we're not exactly sure how it will all play out, it's going to be up to the practices to get it done.”

None of the panel members expressed any financial conflicts related to the screening tool.