Christine Kilgore

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Strategies to increase adherence to headache therapy work best when multiple modalities are used together at every visit throughout the duration of treatment, according to Jeanetta C. Rains, Ph.D., of Elliot Hospital in Manchester, N.H.

"The more comprehensive the approach, the more adherence can be improved," she said at the annual meeting of the Society of Behavioral Medicine.

Relatively few studies have addressed the issue of adherence in headache treatment, but the literature definitively shows that "nonadherence with headache medication regimens is common," said Dr. Rains, who has reviewed the literature on headache treatment compliance and empirically based adherence enhancing strategies.

"And patients who don’t take their medication or who overuse symptomatic medications can aggravate their headache, create a pattern of medication-overuse headache, or transform an episodic headache into a chronic daily headache," said Dr. Rains, who directs the center for sleep evaluation at Elliot Hospital.

One large study of patients with severe headache found that 11% did not fill their initial prescriptions (high cost and concerns about side effects were common reasons) and that 70% did not adhere to their abortive medication regimen.

Other studies have shown that 25%-50% of headache patients do not adhere to their preventive medication regimen, and commonly avoid or delay the use of abortive medication because they want to "wait to see if it’s a migraine or if it’s severe," she said. Concerns about adverse effects and dependency or addiction also are cited as factors in avoiding or delaying use of abortive medications.

This makes education critical. For effective patient education about headache and forms of treatment, physicians should use simple, everyday language; limit instructions to three or four major points; supplement verbal with printed instructions; ask patients to restate the plan; and involve family members or significant others. "And remember, repetition increases retention," she said.

Moreover, "the way we engage is important," Dr. Rains said. Adherence increases "not only when we give more information to patients, but also when we ask patients about their feelings and opinions, and when we praise them when they’re doing well."

She advised forming a collaborative alliance, discussing barriers to treatment, and being supportive of patients who have difficulty meeting their goals. "At the end of a visit, you can ask your patient to rate how important it is for him or her to do the things you’ve been talking about. Then you can ask the patient to rate his or her confidence level for adhering to the treatment plan."

Behavioral strategies can help to target the many psychosocial determinants of adherence, as well as the fact that patients’ motivation for treatment often shifts over time, Dr. Rains said.

She suggested using the following strategies:

• Assess and treat comorbidities and behavioral concerns. Unaddressed depression, anxiety, somatic preoccupation, and low self-efficacy can each affect adherence and subsequent outcomes. "Patients who are depressed, for instance, are three times less likely to take [their prescribed regimens]," she said.

• Simplify the treatment regimen. Studies consistently show that adherence decreases as the number of medications and daily doses increase.

• Consider past behavior and prior experience. Positive prior experiences with medication can enhance response, while negative expectancies may worsen symptoms and amplify side-effects. Differentiating current treatment from past failures is key, she said.

• Predict a positive but realistic outcome.

• Associate any positive outcome to the patient’s behavior and perseverance.

There is no sure way to assess and track adherence accurately, but more objective, multimodal measures are best, Dr. Rains said.

Face-to-face interviewing is the most widely used tool but also the least reliable, as "self-reporting actually overestimates adherence by 30%, compared with more objective monitoring," she said. Diaries and questionnaires are better, and electronic measures are better still. "Yet, even the most objective measures are not entirely reliable," she said. "Studies have shown, for instance, that some patients dump their canisters in anticipation of their visits, and that electronic daily diaries are sometimes completed on the day of their visit."

Mechanical and electronic tools can "remind" patients to take a preset dose and track their use, but these tools do not address a patient’s conscious decision to alter a regimen, she warned.

This is why "a comprehensive, ongoing approach to assessing adherence is important," she said. Physicians generally respond to treatment failures by altering their recommendations for drug choice or for dosing rather than assessing adherence, and this, she emphasized, is a mistake. "All patients," she said, "are candidates for adherence facilitation."

Dr. Rains reported that she had no relevant disclosures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting.

Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well,” Dr. Shuldiner added.

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight.

“Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carbohydrate diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors).

Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin, he said.

Research on the genetics of diabetes is “still in its early days,” said Dr. Shuldiner. The genetic loci associated with type 2 diabetes – and often gestational diabetes – are believed to be responsible for no more than 10% of total genetic susceptibility.

“There may be many rare variants [not detected through the association studies performed thus far] involved, and it's certainly possible that the genetic variants already identified may interact in important ways with lifestyle factors and ultimately with diabetes risk,” he noted.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting.

Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well,” Dr. Shuldiner added.

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight.

“Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carbohydrate diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors).

Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin, he said.

Research on the genetics of diabetes is “still in its early days,” said Dr. Shuldiner. The genetic loci associated with type 2 diabetes – and often gestational diabetes – are believed to be responsible for no more than 10% of total genetic susceptibility.

“There may be many rare variants [not detected through the association studies performed thus far] involved, and it's certainly possible that the genetic variants already identified may interact in important ways with lifestyle factors and ultimately with diabetes risk,” he noted.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Most of the gene variations identified thus far as risk factors for type 2 diabetes also appear to increase risk for gestational diabetes – a trend that reaffirms the importance of taking family histories in obstetrical practice, Dr. Alan R. Shuldiner said.

Hundreds of candidate genes for type 2 diabetes have been analyzed in association studies over the past several years, and more recently, whole genome approaches have identified close to 40 genes with variations that increase the risk of type 2 diabetes, he explained at the meeting.

Moreover, “most of these genetic variants that have also been looked at in [studies of] gestational diabetes all seem to increase risk there as well,” Dr. Shuldiner added.

While the utility of genetic screening in obstetrics needs to be investigated, it's clear that “people who have a family history of type 2 diabetes are probably at increased risk for gestational diabetes,” he said in an interview.

“From a genetic point of view, recent research reaffirms the importance of clinicians asking about family history,” said Dr. Shuldiner, who directs the program in personalized medicine and chairs the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore.

“Until recently, we really didn't know [about this interface],” he said. “It was possible that the genetic factors contributing to gestational diabetes would be very different and distinct from those contributing to type 2 diabetes. So far, that appears not to be the case.”

Most recently, an analysis of more than 5,500 pregnant women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study demonstrated that a common maternal variant of the TCF7L2 gene is associated with a higher risk of gestational diabetes, as defined by the new International Association of Diabetes and Pregnancy Study Groupshand thus a higher risk of adverse pregnancy outcomes, he told meeting participants.

The risk-conferring variants of the TCF7L2 gene appear to be associated with impaired beta-cell function rather than insulin resistance, he noted.

An earlier report on TCF7L2 polymorphisms and progression to diabetes from the Diabetes Prevention Program Research Group showed that patients with the TCF7L2 variant are at increased risk of developing diabetes but “may be superresponders to lifestyle interventions,” Dr. Shuldiner said.

It is findings like these that may, with further research, lead to future recommendations for genetic screening.

Growing evidence on the effects of mutations in the glucokinase (GCK) gene, which appear to account for approximately 5% of gestational diabetes cases in white mothers, may similarly drive screening efforts in the future, he said. (Glucokinase is an enzyme present in pancreatic beta cells required for proper glucose sensing and insulin secretion.)

In a small study conducted in the United Kingdom, maternal hyperglycemia due to a GCK mutation – with no GCK mutation in the fetus – has been shown to result in higher birth weights, while inheritance by the fetus of a paternal GCK mutation appears to result in significant reductions in birth weight.

“Screening for GCK mutations could potentially be useful in guiding therapy so that the baby has a normal birth weight,” said Dr. Shuldiner, also John L. Whitehurst Professor of Medicine and professor of physiology. “The data so far suggest that if both mom and the fetus have a GCK mutation, you may want to forego treatment [with oral hypoglycemic agents or insulin], and even put mom on a high-carbohydrate diet, because the baby needs a high glucose level.”

Glucokinase mutations are also associated with maturity-onset diabetes of the young (MODY), which begins before the age of 25 and which we “now know is a heterogeneous group of disorders” resulting in mutations in any of at least eight different genes, he said.

In fact, many experts refer to MODY as being either “glucokinase diabetes” (resulting from mutations in the gene that encodes the glycolytic enzyme glucokinase) or “transcription factor diabetes” (resulting from mutations in genes that encode various transcription factors).

Unlike GCK MODY, transcription factor MODY is characterized by hyperglycemia that progressively worsens and often requires treatment with oral hypoglycemic agents or insulin, he said.

Research on the genetics of diabetes is “still in its early days,” said Dr. Shuldiner. The genetic loci associated with type 2 diabetes – and often gestational diabetes – are believed to be responsible for no more than 10% of total genetic susceptibility.

“There may be many rare variants [not detected through the association studies performed thus far] involved, and it's certainly possible that the genetic variants already identified may interact in important ways with lifestyle factors and ultimately with diabetes risk,” he noted.

Dr. Shuldiner reported that he had no relevant financial disclosures.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Radical prostatectomy did not significantly reduce the overall rate of all-cause or disease-specific death compared with observation at 12 years in men with clinically localized prostate cancer who participated in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), chief investigator Dr. Timothy J. Wilt has reported.

The surgery does, however, appear to have benefited men with higher prostate-specific antigen (PSA) scores and those with higher-risk disease, Dr. Wilt said.

The yet-to-be-published main results of the PIVOT trial offer a different take on the value of radical prostatectomy from the recently published results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a pre–PSA-era trial that showed a significant overall benefit to surgery, even in men with tumors deemed to be low-risk.

In the PIVOT trial, which enrolled men whose cancer was detected in the early-PSA era, those with lower PSA levels or tumors categorized as low risk clearly gained no benefit from surgery, said Dr. Wilt, professor of medicine at the University of Minnesota, Minneapolis, and core investigator of the Department of Veterans Affairs’ Center for Chronic Disease Outcomes Research.

"Surgery did not reduce mortality [overall and disease specific] more than observation in men with low-PSA or low-risk prostate cancer, but our results do suggest a benefit for surgery in higher-PSA or higher-risk groups," Dr. Wilt reported at the annual meeting of the American Urological Association.

Initiated in 1994, the PIVOT trial randomized 731 men at medical centers across the United States to receive radical prostatectomy (281) or watchful waiting, with palliative care for symptoms. To be eligible, patients had to be 75 years or younger, with clinically localized prostate cancer and a PSA value less than 50 ng/mL.

Their mean age was 67 years, and nearly one-third were African American. Approximately 85% described themselves as fully active. Their mean and median PSA scores were 10.2 ng/mL and 7.8 ng/mL, respectively. Using tumor risk categorizations that incorporated PSA values, Gleason scores, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors.

Investigators completed enrollment in 2002 and followed patients through 2010 (with a median follow-up of 10 years), determining cumulative rates of death at specific time points through intention-to-treat analysis. The new findings come from the final, 12-year analysis.

At the 12-year mark, 354 of the 731 men (48.4%) had died, with absolute reductions in all-cause and disease-specific mortality of approximately 3% in the radical prostatectomy group compared with observation. Specifically, the absolute reduction in all-cause mortality was 2.9% (a hazard ratio of 0.88), and the absolute reduction in prostate cancer mortality was 2.7% (HR, 0.63), values that are not statistically significant, Dr. Wilt said.

The effect of surgery on all-cause and disease-specific mortality did not vary by age, race, self-perceived health status, or the presence of comorbidities. There was also no significant effect of surgery on death rates when men were categorized solely by their Gleason scores (6 or less vs. 7-10).

Prostate cancer mortality did, however, "vary substantially by tumor risk category, ranging from 3% in the low-risk category to 13% in high risk," Dr. Wilt said.

In men with low-risk disease, there was an absolute difference in prostate cancer mortality between the treatment groups of 1.4% in favor of observation. But in men with high-risk disease, the absolute difference was 8.4%, in favor of surgery, a difference that is significant but appears to be of "borderline" statistical significance, Dr. Wilt said after the meeting.

"That’s why we say that our results suggest that there might be a benefit in men with high-risk disease," he said.

One factor challenging the PIVOT trial analyses is variation in some of the pathology readings. While the impact of surgery on prostate cancer mortality for the high-risk group was "consistent whether local or central pathology readings were used [in the sub-analysis]," the benefit of surgery on prostate cancer mortality and all-cause mortality for the intermediate-risk group varied depending on whether local or central pathology readings were employed in the risk categorization and subanalysis, he said.

The impact of surgery was seen most clearly in the PSA-level subgroup. "We consistently found that surgery did not reduce [either all-cause or disease-specific] mortality for men with PSA levels less than or equal to 10, and we consistently found that radical prostatectomy reduced both overall and disease-specific mortality in men with PSAs above 10," he said in the interview.

"Overall, we’re most confident in our findings regarding men with low PSA, low-stage, or low-risk disease," he emphasized.

In men with PSA levels of 10 ng/mL or less, the difference in absolute risk for all-cause mortality was 2.7%, in favor of observation.

Among men whose PSA levels were greater than 10 ng/mL, those randomized to receive radical prostatectomy had a statistically significant 13.2% absolute reduction in all-cause mortality compared with the watchful waiting group, which means that "about 8 men would have to be treated to prevent 1 death in about 12 years," he said after the meeting.

The men enrolled in the PIVOT trial are different from those in the SPCG-4 for various reasons, Dr. Wilt noted. For one, the majority of patients in the Scandinavian trial were diagnosed through palpable tumors or significant urinary obstruction symptoms. "So they had more advanced disease, even though it was still considered clinically localized," he said.

While the PIVOT enrollees are more representative of men being diagnosed and treated in the United States, there still are differences between the early era of PSA testing – the mid-late 1990s, when many of the PIVOT participants were enrolled – and current times, when "nearly all men, for better or for worse, are getting multiple PSA tests and having smaller tumors found earlier," he said.

"The risk of overdiagnosis in the PIVOT study is high, and it’s much higher today," Dr. Wilt said after the meeting. "As we move further and further to finding smaller and smaller tumors that have a very good long-term prognosis even with no treatment ... the risk of overdiagnosis becomes even greater than what we [see in PIVOT.]"

This study was supported by the Department of Veteran Affairs, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Dr. Wilt reported that he had nothing to disclose.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

WASHINGTON – Poorer psychosocial functioning was associated with greater expression of vascular endothelial growth factor – and greater expression, in turn, was associated with shorter disease-free survival – in a small study of patients with newly diagnosed head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines, according to Carolyn Y. Fang, Ph.D., who presented the findings at the annual meeting of the Society of Behavioral Medicine.

She and her team administered a battery of psychosocial questionnaires to assess perceived stress, depressive symptoms, and social support in 37 patients who had been newly diagnosed with HNSCC and sought treatment at the Fox Chase Cancer Center in Philadelphia. Expression of VEGF in tumor tissue that had been obtained during surgery was then evaluated via immunohistochemistry, and was categorized as weak, moderate, or intense.

Higher levels of perceived stress and depressive symptoms were significantly associated with greater VEGF expression in an analysis that controlled for disease stage, Dr. Fang reported. Patients with "intense" VEGF expression, for instance, had a mean perceived stress score that was approximately 47% higher than that of patients with "weak" VEGF expression.

In addition, patients who reported lower levels of social support were more likely to have intense VEGF expression, but this did not reach statistical significance, said Dr. Fang, codirector of the cancer prevention and control program at Fox Chase.

The patients were predominantly male (70.3%) with a mean age of 57 years. Most were married or living with a partner (62%), and half had a high school education or less. Primary tumor sites were the oral cavity (66%), larynx (20%), and oropharynx (14%). More than 40% were classified as having early-stage disease.

A survival analysis looking at two categories of VEGF expression – high and low – and controlling for disease stage and other relevant variables showed that patients with high VEGF expression were more than 2.5 times more likely to die than were those with low expression. "This finding is not a novel finding, but we did confirm here that VEGF expression was associated with disease-free survival," Dr. Fang said in a later interview, noting that follow-up averaged about 5 years.

"At this point, the data on VEGF are preliminary and are just a snapshot in time," Dr. Fang said. "We need to follow this up with a larger longitudinal study in which we can capture the trajectory of psychosocial functioning over time and do multiple assessments of VEGF and other biomarkers [like EGFR] over time."

A combination of previous findings prompted the investigators to do the study. These included reported associations between psychosocial factors and expression of VEGF in patients with other types of cancer, and associations of VEGF with tumor aggressiveness and poor prognosis in HNSCC populations specifically.

Dr. Fang noted that when the patient population was divided into early-stage and late-stage HNSCC, associations among psychosocial functioning and VEGF remained strong for early-stage patients, but were less apparent among late-stage patients.

The psychosocial questionnaires administered in the study were the PSS (Perceived Stress Scale), the CES-D (Center for Epidemiologic Studies–Depression Scale), and the ISEL (Interpersonal Support Evaluation List).

Dr. Fang and her coinvestigators reported having no relevant financial disclosures.

The prevalence of gout has increased in the United States, especially among the eldest population, according to the latest national data. That means that nursing home staff are caring for more hot, swollen, and inflamed joints than ever, said several experts on the topic.

In interviews, they added that clinicians' potential success in preventing, diagnosing, and treating the disease in long-term care residents lies largely in fundamental practices and an individualized approach to medications.

Data from the National Health and Nutrition Examination Survey (NHANES) show an increase in gout prevalence among U.S. adults from 2.7% in the survey's 1994–1998 reporting periods to 3.9% in 2007–2008. Meanwhile, the prevalence in adults aged 80 years and older jumped from 5.9% to 12.6%.

The prevalence of hyperuricemia, which usually precedes gout, was 31% in adults aged 65 years or older and 37% among those aged 80 years and older, according to the latest NHANES data.

The increase in actual gout occurred mainly among men in NHANES. Other studies, however, have documented an increased prevalence of the disease among older women as well. Studies cited in a review of “Crystal-Associated Arthritis in the Elderly” showed women making up at least half of the cases in which gout first strikes after age 60 years. Among individuals who have a first episode after age 80, women seem to predominate (Rheum. Dis. Clin. N. Am. 2007;33:33–55).

The presentation of the disease, as well as its prevalence, is changing, said Dr. Arthur Weinstein, professor of medicine at Georgetown University, Washington, and director of rheumatology at the Washington Hospital Center. “We're seeing more and more polyarticular gout in older patients, for instance, either as an initial presentation or years after just a single monoarticular episode” with no subsequent recurrences, he said in an interview.

He and others said they believe that the common use of thiazide diuretics in older patients is a major driver of gout's changing profile. Other factors could include genetic predispositions to hyperuricemia and gout and increasing obesity, insulin resistance, and metabolic syndrome in the aging population.

While often the best choice for hypertension management, thiazide diuretics can contribute to the development of chronic hyperuricemia, as can low-dose aspirin and cyclosporine. Also, increasing numbers of elderly people have chronic cardiac and renal disease – factors that have been associated with hyperuricemia and gout.

Other changes in gout's presentation in the elderly include earlier and often-atypical development of the soft tissue masses known as tophi and more frequent and earlier involvement of the small joints of the fingers.

Diagnosis, Empiric Therapy

The differential diagnosis of a swollen, inflamed joint often involves ruling out the likelihood of septic arthritis, fracture, or other injury, and pseudogout – the other main form of crystal-induced arthritis.

Patients experiencing an acute gout attack can have a low-grade fever. “But with a fever of 101 or higher, you have to consider that it's something that's not crystal induced,” said Dr. John W. Rachow, a geriatrician and rheumatologist at the University of Iowa, Iowa City.

Septic arthritis should also be suspected when patients have joint pain and tachycardia, hypotension, or signs of other acute illness. “And if there is hardware in the joint, even without a fever, patients should be evaluated at a higher level,” said Dr. Rachow, who also serves as an attending physician in numerous nursing homes in the Iowa City area.

While the diagnostic standard for gout – synovial fluid or tophus aspiration with the identification of monosodium urate crystals under polarizing microscopy – can seem even more important in the older population, it is also more untenable given the stresses of transporting nursing home patients to hospitals.

A good long-term care mind-set can preclude the need for crystal confirmation in every case, said clinicians interviewed for this story.

“In health care, we tend to turn things into acute episodes when they're really acute exacerbations of chronic conditions,” said Dr. George Taler, director of long-term care in the department of medicine at the Washington Hospital Center and medical director of the Capitol Hill Nursing Center, both in Washington.

Diagnosing and treating goutsmean “remembering that our patients have a history,” said Dr. Taler. He advised “making sure that when the nurse calls about a swollen knee, he or she has reviewed the medical record.”

A host of factors can indicate the likelihood that joint pain is a gout attack. These include a history of gout, persistent elevated uric acid levels, and the use of medications or existence of medical conditions associated with gout. Blood testing at the time of an attack is not informative, said Dr. Rachow. While most patients with gout have chronically elevated uric acid levels, serum uric acid levels at the time of an attack are frequently normal, he explained.

Gout should also be considered in elderly patients when attacks of acute pain and swelling are seen in osteoarthritic joints of the fingers, especially in patients who have renal disease or are on chronic diuretic therapy.

An older patient without a history of gout and without any obvious risk for gout or sign of a septic joint probably has pseudogout, which is caused by the deposition of calcium pyrophosphate dihydrate rather than monosodium urate. Pseudogout often strikes the wrist or the knee and does not commonly involve polyarticular attacks, as gout does.

With a suspicion of either gout or pseudogout, a short empiric course of anti-inflammatory treatment should be considered, said Dr. Rachow. “If it really is crystal induced, you'll know in 12 hours and definitely within 24 hours” because the pain will begin to subside, he said.

“And, at that point, if you've started with a nonsteroidal anti-inflammatory and it's working well, you can add a gastroprotective agent and continue the NSAID, reducing the dose once symptoms begin to improve. Or you can switch to colchicine.”

If the anti-inflammatory treatment is “not working spectacularly well within 24 hours, you need to put the brakes on, close your office door, and think things over again,” he said.

Facilities that have a sizable number of patients with frequent flares probably should have a nurse practitioner or a physician assistant trained to aspirate joints and arrange the logistics for sending out samples, Dr. Taler said.

The Longer Term

With a correct approach, “gout is eminently preventable and treatable in 90% of nursing home residents,” said Dr. Weinstein. “The principles are studied, reported, and well described,” he said. The American College of Rheumatology plans to release its first practice guidelines on the management of gout in 2012.

Decisions about managing acute attacks – whether to use NSAIDs, glucocorticoids, or oral colchicine – are rightly driven by the severity of gout and consideration of the patient's coexisting illnesses and the drugs' side effects. While NSAID use carries the risk of gastropathy, colchicine can cause diarrhea and other potentially serious side effects and should be avoided in patients who have renal or hepatic insufficiency.

Many clinicians consider colchicine a second-line therapy for acute gout, after NSAIDs or corticosteroids. In very elderly people, however, the treatment decision might be different. Dr. Weinstein said he worries about possible cardiac risks with the use of NSAIDs in very old patients. He has had success with the early use of low-dose colchicine in very elderly patients with reasonable kidney function, and he said that the drug “works best in the first 48–72 hours.”

Parenteral corticosteroids, intra-articular injections, or even an oral prednisone taper are good options, he emphasized. Issues of whether and how to move from acute management of gout attacks to long-term urate-lowering therapy are taking on added significance in nursing homes as the prevalence of gout increases there.

Dr. Rachow recommended hypouricemic therapy for patients with documented hyperuricemia and a history of multiple attacks, and for patients who have developed tophi. It can even be considered for a frail, ill nursing home resident for whom a second gout attack would be unusually complicating and traumatic, said Dr. Rachow.

When it is deemed beneficial, the urate-lowering therapy must be undertaken with care, he emphasized.

Hypouricemic therapy should start only after an acute attack is completely resolved (or even 2–4 weeks after flare resolution), with cautious dosing and careful monitoring for adverse effects and, when possible, under the cover of a prophylactic anti-inflammatory drug. Low-dose colchicine has long been used to prevent flares associated with the lowering of urate.

Allopurinol, the xanthine oxidase inhibitor most often prescribed to lower urate levels, should be “started low and increased slowly” in older patients with renal impairment, Dr. Weinstein said.

A xanthine oxidase inhibitor called febuxostat (Uloric) was approved in 2009 for treatment of hyperuricemia in patients with gout, but its efficacy and safety compared with allopurinol is not fully established (N. Engl. J. Med. 2011;364: 443–52).

Also on the medication front is a newly approved drug called pegloticase (Krystexxa), which might be a good option for patients who cannot use allopurinol, said Dr. Weinstein.

Dr. Rachow and Dr. Taler said they had no conflicts of interest to disclose on this topic. Dr. Weinstein disclosed that he has received research grants from Savient Pharmaceuticals, the maker of pegloticase, for a clinical study, but not for any therapeutic studies.

The presentation of gout, as well as its prevalence, has been changing.

Source ©craftvision/iStockphoto.com

The prevalence of gout has increased in the United States, especially among the eldest population, according to the latest national data. That means that nursing home staff are caring for more hot, swollen, and inflamed joints than ever, said several experts on the topic.

In interviews, they added that clinicians' potential success in preventing, diagnosing, and treating the disease in long-term care residents lies largely in fundamental practices and an individualized approach to medications.

Data from the National Health and Nutrition Examination Survey (NHANES) show an increase in gout prevalence among U.S. adults from 2.7% in the survey's 1994–1998 reporting periods to 3.9% in 2007–2008. Meanwhile, the prevalence in adults aged 80 years and older jumped from 5.9% to 12.6%.

The prevalence of hyperuricemia, which usually precedes gout, was 31% in adults aged 65 years or older and 37% among those aged 80 years and older, according to the latest NHANES data.

The increase in actual gout occurred mainly among men in NHANES. Other studies, however, have documented an increased prevalence of the disease among older women as well. Studies cited in a review of “Crystal-Associated Arthritis in the Elderly” showed women making up at least half of the cases in which gout first strikes after age 60 years. Among individuals who have a first episode after age 80, women seem to predominate (Rheum. Dis. Clin. N. Am. 2007;33:33–55).

The presentation of the disease, as well as its prevalence, is changing, said Dr. Arthur Weinstein, professor of medicine at Georgetown University, Washington, and director of rheumatology at the Washington Hospital Center. “We're seeing more and more polyarticular gout in older patients, for instance, either as an initial presentation or years after just a single monoarticular episode” with no subsequent recurrences, he said in an interview.

He and others said they believe that the common use of thiazide diuretics in older patients is a major driver of gout's changing profile. Other factors could include genetic predispositions to hyperuricemia and gout and increasing obesity, insulin resistance, and metabolic syndrome in the aging population.

While often the best choice for hypertension management, thiazide diuretics can contribute to the development of chronic hyperuricemia, as can low-dose aspirin and cyclosporine. Also, increasing numbers of elderly people have chronic cardiac and renal disease – factors that have been associated with hyperuricemia and gout.

Other changes in gout's presentation in the elderly include earlier and often-atypical development of the soft tissue masses known as tophi and more frequent and earlier involvement of the small joints of the fingers.

Diagnosis, Empiric Therapy

The differential diagnosis of a swollen, inflamed joint often involves ruling out the likelihood of septic arthritis, fracture, or other injury, and pseudogout – the other main form of crystal-induced arthritis.

Patients experiencing an acute gout attack can have a low-grade fever. “But with a fever of 101 or higher, you have to consider that it's something that's not crystal induced,” said Dr. John W. Rachow, a geriatrician and rheumatologist at the University of Iowa, Iowa City.

Septic arthritis should also be suspected when patients have joint pain and tachycardia, hypotension, or signs of other acute illness. “And if there is hardware in the joint, even without a fever, patients should be evaluated at a higher level,” said Dr. Rachow, who also serves as an attending physician in numerous nursing homes in the Iowa City area.

While the diagnostic standard for gout – synovial fluid or tophus aspiration with the identification of monosodium urate crystals under polarizing microscopy – can seem even more important in the older population, it is also more untenable given the stresses of transporting nursing home patients to hospitals.

A good long-term care mind-set can preclude the need for crystal confirmation in every case, said clinicians interviewed for this story.

“In health care, we tend to turn things into acute episodes when they're really acute exacerbations of chronic conditions,” said Dr. George Taler, director of long-term care in the department of medicine at the Washington Hospital Center and medical director of the Capitol Hill Nursing Center, both in Washington.

Diagnosing and treating goutsmean “remembering that our patients have a history,” said Dr. Taler. He advised “making sure that when the nurse calls about a swollen knee, he or she has reviewed the medical record.”

A host of factors can indicate the likelihood that joint pain is a gout attack. These include a history of gout, persistent elevated uric acid levels, and the use of medications or existence of medical conditions associated with gout. Blood testing at the time of an attack is not informative, said Dr. Rachow. While most patients with gout have chronically elevated uric acid levels, serum uric acid levels at the time of an attack are frequently normal, he explained.

Gout should also be considered in elderly patients when attacks of acute pain and swelling are seen in osteoarthritic joints of the fingers, especially in patients who have renal disease or are on chronic diuretic therapy.

An older patient without a history of gout and without any obvious risk for gout or sign of a septic joint probably has pseudogout, which is caused by the deposition of calcium pyrophosphate dihydrate rather than monosodium urate. Pseudogout often strikes the wrist or the knee and does not commonly involve polyarticular attacks, as gout does.

With a suspicion of either gout or pseudogout, a short empiric course of anti-inflammatory treatment should be considered, said Dr. Rachow. “If it really is crystal induced, you'll know in 12 hours and definitely within 24 hours” because the pain will begin to subside, he said.

“And, at that point, if you've started with a nonsteroidal anti-inflammatory and it's working well, you can add a gastroprotective agent and continue the NSAID, reducing the dose once symptoms begin to improve. Or you can switch to colchicine.”

If the anti-inflammatory treatment is “not working spectacularly well within 24 hours, you need to put the brakes on, close your office door, and think things over again,” he said.

Facilities that have a sizable number of patients with frequent flares probably should have a nurse practitioner or a physician assistant trained to aspirate joints and arrange the logistics for sending out samples, Dr. Taler said.

The Longer Term

With a correct approach, “gout is eminently preventable and treatable in 90% of nursing home residents,” said Dr. Weinstein. “The principles are studied, reported, and well described,” he said. The American College of Rheumatology plans to release its first practice guidelines on the management of gout in 2012.

Decisions about managing acute attacks – whether to use NSAIDs, glucocorticoids, or oral colchicine – are rightly driven by the severity of gout and consideration of the patient's coexisting illnesses and the drugs' side effects. While NSAID use carries the risk of gastropathy, colchicine can cause diarrhea and other potentially serious side effects and should be avoided in patients who have renal or hepatic insufficiency.

Many clinicians consider colchicine a second-line therapy for acute gout, after NSAIDs or corticosteroids. In very elderly people, however, the treatment decision might be different. Dr. Weinstein said he worries about possible cardiac risks with the use of NSAIDs in very old patients. He has had success with the early use of low-dose colchicine in very elderly patients with reasonable kidney function, and he said that the drug “works best in the first 48–72 hours.”

Parenteral corticosteroids, intra-articular injections, or even an oral prednisone taper are good options, he emphasized. Issues of whether and how to move from acute management of gout attacks to long-term urate-lowering therapy are taking on added significance in nursing homes as the prevalence of gout increases there.

Dr. Rachow recommended hypouricemic therapy for patients with documented hyperuricemia and a history of multiple attacks, and for patients who have developed tophi. It can even be considered for a frail, ill nursing home resident for whom a second gout attack would be unusually complicating and traumatic, said Dr. Rachow.

When it is deemed beneficial, the urate-lowering therapy must be undertaken with care, he emphasized.

Hypouricemic therapy should start only after an acute attack is completely resolved (or even 2–4 weeks after flare resolution), with cautious dosing and careful monitoring for adverse effects and, when possible, under the cover of a prophylactic anti-inflammatory drug. Low-dose colchicine has long been used to prevent flares associated with the lowering of urate.

Allopurinol, the xanthine oxidase inhibitor most often prescribed to lower urate levels, should be “started low and increased slowly” in older patients with renal impairment, Dr. Weinstein said.

A xanthine oxidase inhibitor called febuxostat (Uloric) was approved in 2009 for treatment of hyperuricemia in patients with gout, but its efficacy and safety compared with allopurinol is not fully established (N. Engl. J. Med. 2011;364: 443–52).

Also on the medication front is a newly approved drug called pegloticase (Krystexxa), which might be a good option for patients who cannot use allopurinol, said Dr. Weinstein.

Dr. Rachow and Dr. Taler said they had no conflicts of interest to disclose on this topic. Dr. Weinstein disclosed that he has received research grants from Savient Pharmaceuticals, the maker of pegloticase, for a clinical study, but not for any therapeutic studies.

The presentation of gout, as well as its prevalence, has been changing.

Source ©craftvision/iStockphoto.com

The prevalence of gout has increased in the United States, especially among the eldest population, according to the latest national data. That means that nursing home staff are caring for more hot, swollen, and inflamed joints than ever, said several experts on the topic.

In interviews, they added that clinicians' potential success in preventing, diagnosing, and treating the disease in long-term care residents lies largely in fundamental practices and an individualized approach to medications.

Data from the National Health and Nutrition Examination Survey (NHANES) show an increase in gout prevalence among U.S. adults from 2.7% in the survey's 1994–1998 reporting periods to 3.9% in 2007–2008. Meanwhile, the prevalence in adults aged 80 years and older jumped from 5.9% to 12.6%.

The prevalence of hyperuricemia, which usually precedes gout, was 31% in adults aged 65 years or older and 37% among those aged 80 years and older, according to the latest NHANES data.

The increase in actual gout occurred mainly among men in NHANES. Other studies, however, have documented an increased prevalence of the disease among older women as well. Studies cited in a review of “Crystal-Associated Arthritis in the Elderly” showed women making up at least half of the cases in which gout first strikes after age 60 years. Among individuals who have a first episode after age 80, women seem to predominate (Rheum. Dis. Clin. N. Am. 2007;33:33–55).

The presentation of the disease, as well as its prevalence, is changing, said Dr. Arthur Weinstein, professor of medicine at Georgetown University, Washington, and director of rheumatology at the Washington Hospital Center. “We're seeing more and more polyarticular gout in older patients, for instance, either as an initial presentation or years after just a single monoarticular episode” with no subsequent recurrences, he said in an interview.

He and others said they believe that the common use of thiazide diuretics in older patients is a major driver of gout's changing profile. Other factors could include genetic predispositions to hyperuricemia and gout and increasing obesity, insulin resistance, and metabolic syndrome in the aging population.

While often the best choice for hypertension management, thiazide diuretics can contribute to the development of chronic hyperuricemia, as can low-dose aspirin and cyclosporine. Also, increasing numbers of elderly people have chronic cardiac and renal disease – factors that have been associated with hyperuricemia and gout.

Other changes in gout's presentation in the elderly include earlier and often-atypical development of the soft tissue masses known as tophi and more frequent and earlier involvement of the small joints of the fingers.

Diagnosis, Empiric Therapy

The differential diagnosis of a swollen, inflamed joint often involves ruling out the likelihood of septic arthritis, fracture, or other injury, and pseudogout – the other main form of crystal-induced arthritis.

Patients experiencing an acute gout attack can have a low-grade fever. “But with a fever of 101 or higher, you have to consider that it's something that's not crystal induced,” said Dr. John W. Rachow, a geriatrician and rheumatologist at the University of Iowa, Iowa City.

Septic arthritis should also be suspected when patients have joint pain and tachycardia, hypotension, or signs of other acute illness. “And if there is hardware in the joint, even without a fever, patients should be evaluated at a higher level,” said Dr. Rachow, who also serves as an attending physician in numerous nursing homes in the Iowa City area.

While the diagnostic standard for gout – synovial fluid or tophus aspiration with the identification of monosodium urate crystals under polarizing microscopy – can seem even more important in the older population, it is also more untenable given the stresses of transporting nursing home patients to hospitals.

A good long-term care mind-set can preclude the need for crystal confirmation in every case, said clinicians interviewed for this story.

“In health care, we tend to turn things into acute episodes when they're really acute exacerbations of chronic conditions,” said Dr. George Taler, director of long-term care in the department of medicine at the Washington Hospital Center and medical director of the Capitol Hill Nursing Center, both in Washington.

Diagnosing and treating goutsmean “remembering that our patients have a history,” said Dr. Taler. He advised “making sure that when the nurse calls about a swollen knee, he or she has reviewed the medical record.”

A host of factors can indicate the likelihood that joint pain is a gout attack. These include a history of gout, persistent elevated uric acid levels, and the use of medications or existence of medical conditions associated with gout. Blood testing at the time of an attack is not informative, said Dr. Rachow. While most patients with gout have chronically elevated uric acid levels, serum uric acid levels at the time of an attack are frequently normal, he explained.

Gout should also be considered in elderly patients when attacks of acute pain and swelling are seen in osteoarthritic joints of the fingers, especially in patients who have renal disease or are on chronic diuretic therapy.

An older patient without a history of gout and without any obvious risk for gout or sign of a septic joint probably has pseudogout, which is caused by the deposition of calcium pyrophosphate dihydrate rather than monosodium urate. Pseudogout often strikes the wrist or the knee and does not commonly involve polyarticular attacks, as gout does.

With a suspicion of either gout or pseudogout, a short empiric course of anti-inflammatory treatment should be considered, said Dr. Rachow. “If it really is crystal induced, you'll know in 12 hours and definitely within 24 hours” because the pain will begin to subside, he said.

“And, at that point, if you've started with a nonsteroidal anti-inflammatory and it's working well, you can add a gastroprotective agent and continue the NSAID, reducing the dose once symptoms begin to improve. Or you can switch to colchicine.”

If the anti-inflammatory treatment is “not working spectacularly well within 24 hours, you need to put the brakes on, close your office door, and think things over again,” he said.

Facilities that have a sizable number of patients with frequent flares probably should have a nurse practitioner or a physician assistant trained to aspirate joints and arrange the logistics for sending out samples, Dr. Taler said.

The Longer Term

With a correct approach, “gout is eminently preventable and treatable in 90% of nursing home residents,” said Dr. Weinstein. “The principles are studied, reported, and well described,” he said. The American College of Rheumatology plans to release its first practice guidelines on the management of gout in 2012.

Decisions about managing acute attacks – whether to use NSAIDs, glucocorticoids, or oral colchicine – are rightly driven by the severity of gout and consideration of the patient's coexisting illnesses and the drugs' side effects. While NSAID use carries the risk of gastropathy, colchicine can cause diarrhea and other potentially serious side effects and should be avoided in patients who have renal or hepatic insufficiency.

Many clinicians consider colchicine a second-line therapy for acute gout, after NSAIDs or corticosteroids. In very elderly people, however, the treatment decision might be different. Dr. Weinstein said he worries about possible cardiac risks with the use of NSAIDs in very old patients. He has had success with the early use of low-dose colchicine in very elderly patients with reasonable kidney function, and he said that the drug “works best in the first 48–72 hours.”

Parenteral corticosteroids, intra-articular injections, or even an oral prednisone taper are good options, he emphasized. Issues of whether and how to move from acute management of gout attacks to long-term urate-lowering therapy are taking on added significance in nursing homes as the prevalence of gout increases there.

Dr. Rachow recommended hypouricemic therapy for patients with documented hyperuricemia and a history of multiple attacks, and for patients who have developed tophi. It can even be considered for a frail, ill nursing home resident for whom a second gout attack would be unusually complicating and traumatic, said Dr. Rachow.

When it is deemed beneficial, the urate-lowering therapy must be undertaken with care, he emphasized.

Hypouricemic therapy should start only after an acute attack is completely resolved (or even 2–4 weeks after flare resolution), with cautious dosing and careful monitoring for adverse effects and, when possible, under the cover of a prophylactic anti-inflammatory drug. Low-dose colchicine has long been used to prevent flares associated with the lowering of urate.

Allopurinol, the xanthine oxidase inhibitor most often prescribed to lower urate levels, should be “started low and increased slowly” in older patients with renal impairment, Dr. Weinstein said.

A xanthine oxidase inhibitor called febuxostat (Uloric) was approved in 2009 for treatment of hyperuricemia in patients with gout, but its efficacy and safety compared with allopurinol is not fully established (N. Engl. J. Med. 2011;364: 443–52).

Also on the medication front is a newly approved drug called pegloticase (Krystexxa), which might be a good option for patients who cannot use allopurinol, said Dr. Weinstein.

Dr. Rachow and Dr. Taler said they had no conflicts of interest to disclose on this topic. Dr. Weinstein disclosed that he has received research grants from Savient Pharmaceuticals, the maker of pegloticase, for a clinical study, but not for any therapeutic studies.

The presentation of gout, as well as its prevalence, has been changing.

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