Kate Johnson

ORLANDO — Pain is a comorbid condition too often overlooked in the setting of geriatric psychiatry, despite the potential for better mental health outcomes when it is treated, Dr. Jordan F. Karp said at the annual meeting of the American Association for Geriatric Psychiatry.

“I don't think enough attention is paid to assessing, diagnosing, and managing pain by many psychiatrists and other physicians who treat older adults,” he said in an interview. “I highly doubt that clinicians are aware of the effects of pain on cognition.”

Because pain has reached “epidemic” proportions among the elderly and can significantly worsen cognition and depression, it should be assessed and treated routinely as part of the psychiatric management of this population, said Dr. Karp, medical director of geriatric psychiatry at one of the referral pain clinics at the University of Pittsburgh Medical Center.

Studies suggest that up to 50% of community-dwelling seniors experience pain that interferes with normal functioning, and up to 80% of nursing home patients live with undertreated pain—the source of which can be musculoskeletal, neuropathic, visceral, metabolic, or other. (See box.)

It is well known that persistent pain limits mobility, increases the risk of falls, and can lead to social isolation, but it is not always appreciated that pain can also increase anxiety, depression, and cognitive impairment, said Dr. Karp, who has a clinical and research focus on both pain and affective disorders in older adults. He disclosed his advisory role with Eli Lilly & Co. and Myriad Genetics Inc.

In a recent survey of 56 patients in an older adult pain management program, he showed that higher pain severity was associated with poorer performance on a test of number/letter switching (Pain Med. 2006;7:444–52).

In another study of older adults (mean age 73 years), different investigators demonstrated lower neuropsychological function among 163 subjects with chronic low back pain (CLBP), compared with 163 who were pain free (Pain Med. 2006;7:60–70). Recent preliminary evidence also suggests reduced brain volume among eight seniors with CLBP, compared with eight who were pain free (Pain Med. 2008;9:240–8).

The comorbidity of pain and depression is a vicious circle, Dr. Thomas Meeks of the University of California, San Diego, said in a separate presentation at the meeting.

A link between depression and immune system dysfunction has been described, and both pain and weakened immunity have been associated with an increase in inflammatory cytokines. Inflammatory cytokines are also associated with anorexia, sleep disturbance, and fatigue and have been shown to negatively affect brain chemicals such as serotonin and norepinephrine, suggesting “there may be a role of inflammatory cytokines in late-life depression,” he said.

Since the rise in inflammatory cytokines seen with acute pain can persist long after the source of the pain has been corrected, prompt diagnosis and treatment of pain is important to reduce the risk of persistent pain and chronic depression, Dr. Meeks said.

“We need to keep pain in mind and ask our patients about it,” said Dr. Karp. In addition to various visual or verbal rating scales that can be used to inquire about pain, he said, certain direct questions might be helpful:

▸ Are you in pain now, or if not now, do you hurt more often than not?

▸ Where do you hurt?

▸ How has pain interfered with your life?

▸ Does pain interfere with your sleep?

“Insomnia is ubiquitous in this group,” he said. “It has been associated with a decreased pain threshold, and it decreases patients' ability to actively cope with their pain problem.”

Preliminary analysis from some of his pilot work has shown that insomnia and fatigue among older patients are associated with passive rather than active coping skills. “Passive skills are less effective and involve things like catastrophizing, praying, or hoping the pain will stop, whereas more active coping involves increasing behavioral activities and using coping self-statements like 'I will get through this,' 'the pain will pass,' or 'the pain will not kill me,'” he said.

When direct questioning is not useful or patients are nonverbal, behavioral observation can reveal a great deal about the pain an individual may be experiencing. “They may be grimacing or sighing; they may be irritable, disruptive, or verbally abusive; their body position may be rigid or guarded; or they might show their discomfort by fidgeting,” said Dr. Karp.

The recently validated Elderly Pain Caring Assessment 2 provides further insight into nonverbal cues (Pain 2007;133:87–98). “It's unlikely that we are going to be able to introduce another assessment into our nursing homes, but informing staff about some of these probes may be useful,” he said.

Regardless of whether patients live in the community or in a nursing home, treating their pain with opioids can raise concerns about sedation and cognitive impairment. The decision should involve an individualized risk-benefit analysis. “While opioids do increase the risk of sedation, confusion, falls, and constipation, for some people the analgesia that results outweighs these potential risks—and cognition actually seems to improve,” he said. “Perhaps they are less distracted by pain and are better able to focus and concentrate.”

Health care professionals should regard persistent pain in the elderly as treatable, with the potential for improvement in many patients. “We need to get the word out that the management of pain should be moved up the priority list, because we can get these patients feeling and functioning better,” Dr. Karp said.

Common Sources Of Geriatric Pain

Musculoskeletal

Degenerative joint disease

Spinal stenosis

Fractures

Improper positioning

Contractures

Visceral

Coronary artery disease

Urinary retention

Constipation

Neuropathic

Postherpetic neuralgia

Radiculopathy

Poststroke syndrome

Diabetic neuropathic pain

Metabolic

Vitamin D deficiency

Paget's disease

Other

Cancer

Fibromyalgia

Oral/dental disorder

Peripheral vascular disease

Polymyalgia rheumatica

ORLANDO — Pain is a comorbid condition too often overlooked in the setting of geriatric psychiatry, despite the potential for better mental health outcomes when it is treated, Dr. Jordan F. Karp said at the annual meeting of the American Association for Geriatric Psychiatry.

“I don't think enough attention is paid to assessing, diagnosing, and managing pain by many psychiatrists and other physicians who treat older adults,” he said in an interview. “I highly doubt that clinicians are aware of the effects of pain on cognition.”

Because pain has reached “epidemic” proportions among the elderly and can significantly worsen cognition and depression, it should be assessed and treated routinely as part of the psychiatric management of this population, said Dr. Karp, medical director of geriatric psychiatry at one of the referral pain clinics at the University of Pittsburgh Medical Center.

Studies suggest that up to 50% of community-dwelling seniors experience pain that interferes with normal functioning, and up to 80% of nursing home patients live with undertreated pain—the source of which can be musculoskeletal, neuropathic, visceral, metabolic, or other. (See box.)

It is well known that persistent pain limits mobility, increases the risk of falls, and can lead to social isolation, but it is not always appreciated that pain can also increase anxiety, depression, and cognitive impairment, said Dr. Karp, who has a clinical and research focus on both pain and affective disorders in older adults. He disclosed his advisory role with Eli Lilly & Co. and Myriad Genetics Inc.

In a recent survey of 56 patients in an older adult pain management program, he showed that higher pain severity was associated with poorer performance on a test of number/letter switching (Pain Med. 2006;7:444–52).

In another study of older adults (mean age 73 years), different investigators demonstrated lower neuropsychological function among 163 subjects with chronic low back pain (CLBP), compared with 163 who were pain free (Pain Med. 2006;7:60–70). Recent preliminary evidence also suggests reduced brain volume among eight seniors with CLBP, compared with eight who were pain free (Pain Med. 2008;9:240–8).

The comorbidity of pain and depression is a vicious circle, Dr. Thomas Meeks of the University of California, San Diego, said in a separate presentation at the meeting.

A link between depression and immune system dysfunction has been described, and both pain and weakened immunity have been associated with an increase in inflammatory cytokines. Inflammatory cytokines are also associated with anorexia, sleep disturbance, and fatigue and have been shown to negatively affect brain chemicals such as serotonin and norepinephrine, suggesting “there may be a role of inflammatory cytokines in late-life depression,” he said.

Since the rise in inflammatory cytokines seen with acute pain can persist long after the source of the pain has been corrected, prompt diagnosis and treatment of pain is important to reduce the risk of persistent pain and chronic depression, Dr. Meeks said.

“We need to keep pain in mind and ask our patients about it,” said Dr. Karp. In addition to various visual or verbal rating scales that can be used to inquire about pain, he said, certain direct questions might be helpful:

▸ Are you in pain now, or if not now, do you hurt more often than not?

▸ Where do you hurt?

▸ How has pain interfered with your life?

▸ Does pain interfere with your sleep?

“Insomnia is ubiquitous in this group,” he said. “It has been associated with a decreased pain threshold, and it decreases patients' ability to actively cope with their pain problem.”

Preliminary analysis from some of his pilot work has shown that insomnia and fatigue among older patients are associated with passive rather than active coping skills. “Passive skills are less effective and involve things like catastrophizing, praying, or hoping the pain will stop, whereas more active coping involves increasing behavioral activities and using coping self-statements like 'I will get through this,' 'the pain will pass,' or 'the pain will not kill me,'” he said.

When direct questioning is not useful or patients are nonverbal, behavioral observation can reveal a great deal about the pain an individual may be experiencing. “They may be grimacing or sighing; they may be irritable, disruptive, or verbally abusive; their body position may be rigid or guarded; or they might show their discomfort by fidgeting,” said Dr. Karp.

The recently validated Elderly Pain Caring Assessment 2 provides further insight into nonverbal cues (Pain 2007;133:87–98). “It's unlikely that we are going to be able to introduce another assessment into our nursing homes, but informing staff about some of these probes may be useful,” he said.

Regardless of whether patients live in the community or in a nursing home, treating their pain with opioids can raise concerns about sedation and cognitive impairment. The decision should involve an individualized risk-benefit analysis. “While opioids do increase the risk of sedation, confusion, falls, and constipation, for some people the analgesia that results outweighs these potential risks—and cognition actually seems to improve,” he said. “Perhaps they are less distracted by pain and are better able to focus and concentrate.”

Health care professionals should regard persistent pain in the elderly as treatable, with the potential for improvement in many patients. “We need to get the word out that the management of pain should be moved up the priority list, because we can get these patients feeling and functioning better,” Dr. Karp said.

Common Sources Of Geriatric Pain

Musculoskeletal

Degenerative joint disease

Spinal stenosis

Fractures

Improper positioning

Contractures

Visceral

Coronary artery disease

Urinary retention

Constipation

Neuropathic

Postherpetic neuralgia

Radiculopathy

Poststroke syndrome

Diabetic neuropathic pain

Metabolic

Vitamin D deficiency

Paget's disease

Other

Cancer

Fibromyalgia

Oral/dental disorder

Peripheral vascular disease

Polymyalgia rheumatica

ORLANDO — Pain is a comorbid condition too often overlooked in the setting of geriatric psychiatry, despite the potential for better mental health outcomes when it is treated, Dr. Jordan F. Karp said at the annual meeting of the American Association for Geriatric Psychiatry.

“I don't think enough attention is paid to assessing, diagnosing, and managing pain by many psychiatrists and other physicians who treat older adults,” he said in an interview. “I highly doubt that clinicians are aware of the effects of pain on cognition.”

Because pain has reached “epidemic” proportions among the elderly and can significantly worsen cognition and depression, it should be assessed and treated routinely as part of the psychiatric management of this population, said Dr. Karp, medical director of geriatric psychiatry at one of the referral pain clinics at the University of Pittsburgh Medical Center.

Studies suggest that up to 50% of community-dwelling seniors experience pain that interferes with normal functioning, and up to 80% of nursing home patients live with undertreated pain—the source of which can be musculoskeletal, neuropathic, visceral, metabolic, or other. (See box.)

It is well known that persistent pain limits mobility, increases the risk of falls, and can lead to social isolation, but it is not always appreciated that pain can also increase anxiety, depression, and cognitive impairment, said Dr. Karp, who has a clinical and research focus on both pain and affective disorders in older adults. He disclosed his advisory role with Eli Lilly & Co. and Myriad Genetics Inc.

In a recent survey of 56 patients in an older adult pain management program, he showed that higher pain severity was associated with poorer performance on a test of number/letter switching (Pain Med. 2006;7:444–52).

In another study of older adults (mean age 73 years), different investigators demonstrated lower neuropsychological function among 163 subjects with chronic low back pain (CLBP), compared with 163 who were pain free (Pain Med. 2006;7:60–70). Recent preliminary evidence also suggests reduced brain volume among eight seniors with CLBP, compared with eight who were pain free (Pain Med. 2008;9:240–8).

The comorbidity of pain and depression is a vicious circle, Dr. Thomas Meeks of the University of California, San Diego, said in a separate presentation at the meeting.

A link between depression and immune system dysfunction has been described, and both pain and weakened immunity have been associated with an increase in inflammatory cytokines. Inflammatory cytokines are also associated with anorexia, sleep disturbance, and fatigue and have been shown to negatively affect brain chemicals such as serotonin and norepinephrine, suggesting “there may be a role of inflammatory cytokines in late-life depression,” he said.

Since the rise in inflammatory cytokines seen with acute pain can persist long after the source of the pain has been corrected, prompt diagnosis and treatment of pain is important to reduce the risk of persistent pain and chronic depression, Dr. Meeks said.

“We need to keep pain in mind and ask our patients about it,” said Dr. Karp. In addition to various visual or verbal rating scales that can be used to inquire about pain, he said, certain direct questions might be helpful:

▸ Are you in pain now, or if not now, do you hurt more often than not?

▸ Where do you hurt?

▸ How has pain interfered with your life?

▸ Does pain interfere with your sleep?

“Insomnia is ubiquitous in this group,” he said. “It has been associated with a decreased pain threshold, and it decreases patients' ability to actively cope with their pain problem.”

Preliminary analysis from some of his pilot work has shown that insomnia and fatigue among older patients are associated with passive rather than active coping skills. “Passive skills are less effective and involve things like catastrophizing, praying, or hoping the pain will stop, whereas more active coping involves increasing behavioral activities and using coping self-statements like 'I will get through this,' 'the pain will pass,' or 'the pain will not kill me,'” he said.

When direct questioning is not useful or patients are nonverbal, behavioral observation can reveal a great deal about the pain an individual may be experiencing. “They may be grimacing or sighing; they may be irritable, disruptive, or verbally abusive; their body position may be rigid or guarded; or they might show their discomfort by fidgeting,” said Dr. Karp.

The recently validated Elderly Pain Caring Assessment 2 provides further insight into nonverbal cues (Pain 2007;133:87–98). “It's unlikely that we are going to be able to introduce another assessment into our nursing homes, but informing staff about some of these probes may be useful,” he said.

Regardless of whether patients live in the community or in a nursing home, treating their pain with opioids can raise concerns about sedation and cognitive impairment. The decision should involve an individualized risk-benefit analysis. “While opioids do increase the risk of sedation, confusion, falls, and constipation, for some people the analgesia that results outweighs these potential risks—and cognition actually seems to improve,” he said. “Perhaps they are less distracted by pain and are better able to focus and concentrate.”

Health care professionals should regard persistent pain in the elderly as treatable, with the potential for improvement in many patients. “We need to get the word out that the management of pain should be moved up the priority list, because we can get these patients feeling and functioning better,” Dr. Karp said.

Common Sources Of Geriatric Pain

Musculoskeletal

Degenerative joint disease

Spinal stenosis

Fractures

Improper positioning

Contractures

Visceral

Coronary artery disease

Urinary retention

Constipation

Neuropathic

Postherpetic neuralgia

Radiculopathy

Poststroke syndrome

Diabetic neuropathic pain

Metabolic

Vitamin D deficiency

Paget's disease

Other

Cancer

Fibromyalgia

Oral/dental disorder

Peripheral vascular disease

Polymyalgia rheumatica

Patients with irritable bowel syndrome have altered brain responses to the anticipation of pain and to pain itself, which might make them more sensitive to painful stimuli, reported Dr. Steven M. Berman and his colleagues from the Center for the Neurobiology of Stress at the University of California, Los Angeles.

During expectation of pain, irritable bowel syndrome patients generate higher levels of tonic noradrenergic activity, producing a bias toward interpretation of network activity as pain, and are inefficient at reducing such activity when discrimination of nonpainful stimulation should be maximized, they said (J. Neurosci. 2008;28:349–59).

Functional magnetic resonance imaging (fMRI) was used to measure the blood oxygen level-dependent response to anticipated and delivered rectal distention in 14 female IBS patients and 12 healthy controls (mean age 36 years). When controls were anticipating a painful stimulus, brain activity decreased in several regions, but there was less of this anticipatory deactivation in the IBS patients.

Visceral distention of the rectum was then performed using a computer-driven pump and rectal balloon. Four to six sessions of 16 inflations were performed. Each inflation was preceded by an anticipatory cue. During rectal distention, increases in activity in the insula, dorsal anterior cingulate cortex, and dorsal brainstem were more extensive in IBS patients than in controls.

The results show that during expectation of experimental abdominal/pelvic discomfort, female IBS patients are more anxious and less able than healthy controls to downregulate activity within the CNS network activated by potentially aversive stimuli, the authors noted.

Patients with irritable bowel syndrome have altered brain responses to the anticipation of pain and to pain itself, which might make them more sensitive to painful stimuli, reported Dr. Steven M. Berman and his colleagues from the Center for the Neurobiology of Stress at the University of California, Los Angeles.

During expectation of pain, irritable bowel syndrome patients generate higher levels of tonic noradrenergic activity, producing a bias toward interpretation of network activity as pain, and are inefficient at reducing such activity when discrimination of nonpainful stimulation should be maximized, they said (J. Neurosci. 2008;28:349–59).

Functional magnetic resonance imaging (fMRI) was used to measure the blood oxygen level-dependent response to anticipated and delivered rectal distention in 14 female IBS patients and 12 healthy controls (mean age 36 years). When controls were anticipating a painful stimulus, brain activity decreased in several regions, but there was less of this anticipatory deactivation in the IBS patients.

Visceral distention of the rectum was then performed using a computer-driven pump and rectal balloon. Four to six sessions of 16 inflations were performed. Each inflation was preceded by an anticipatory cue. During rectal distention, increases in activity in the insula, dorsal anterior cingulate cortex, and dorsal brainstem were more extensive in IBS patients than in controls.

The results show that during expectation of experimental abdominal/pelvic discomfort, female IBS patients are more anxious and less able than healthy controls to downregulate activity within the CNS network activated by potentially aversive stimuli, the authors noted.

Patients with irritable bowel syndrome have altered brain responses to the anticipation of pain and to pain itself, which might make them more sensitive to painful stimuli, reported Dr. Steven M. Berman and his colleagues from the Center for the Neurobiology of Stress at the University of California, Los Angeles.

During expectation of pain, irritable bowel syndrome patients generate higher levels of tonic noradrenergic activity, producing a bias toward interpretation of network activity as pain, and are inefficient at reducing such activity when discrimination of nonpainful stimulation should be maximized, they said (J. Neurosci. 2008;28:349–59).

Functional magnetic resonance imaging (fMRI) was used to measure the blood oxygen level-dependent response to anticipated and delivered rectal distention in 14 female IBS patients and 12 healthy controls (mean age 36 years). When controls were anticipating a painful stimulus, brain activity decreased in several regions, but there was less of this anticipatory deactivation in the IBS patients.

Visceral distention of the rectum was then performed using a computer-driven pump and rectal balloon. Four to six sessions of 16 inflations were performed. Each inflation was preceded by an anticipatory cue. During rectal distention, increases in activity in the insula, dorsal anterior cingulate cortex, and dorsal brainstem were more extensive in IBS patients than in controls.

The results show that during expectation of experimental abdominal/pelvic discomfort, female IBS patients are more anxious and less able than healthy controls to downregulate activity within the CNS network activated by potentially aversive stimuli, the authors noted.

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.

MONTREAL — The escalating numbers of new and existing hepatitis C infections in Canada are reinforcing the evidence of a U.S. epidemic, Dr. Robert P. Myers said at Canadian Digestive Diseases Week.

“The burden of hepatitis C has grown dramatically in the past decade,” said Dr. Myers of the University of Calgary (Alta). “It is vital that we continue with preventive measures and maximize treatment.”

By using an administrative hospitalization database from the Calgary Health Region, Dr. Myers identified 4,002 hospitalizations related to hepatitis C virus (HCV) infection between 1994 and 2004, 22% of which (869 cases) were HCV liver-related, he reported. Among this group of patients, 67% were male, with a median age of 50 years.

With a concentration on number of hospitalizations, length of hospital stay, and in-hospital mortality, Dr. Myers documented an approximate fourfold increase over the 11-year period. Hospital charges for this population also increased an average of 41% between 2000 and 2004, which was attributable to more admissions rather than longer hospital stays. The length of stay actually stabilized during this period, at an average of 7 days, he said.

“We project if this rate continues in a linear fashion that by 2020, across Canada, about $240 million [Canadian] will be spent on hepatitis C liver-related hospitalizations,” he said.

Patient subgroups that were identified as particularly high risk included females, who represented 25% of the hospitalizations at the beginning of the study period but increased to 35% by the end, for an average annual increase of 19%.

“Interestingly, if you compare that to the males, somewhat counterintuitively males had a lower annual growth rate in hospitalizations of 13.1%,” he said. “The etiology of that is a bit unclear, but it may perhaps be due to underreporting at the beginning of the study.” He noted that even when adjustments were made to account for underreporting, the findings remained significant.

Other high-risk groups were patients aged 40–59 years, for whom hospitalizations increased more than in any other age group, at 19% annually, and HIV-coinfected patients. The latter accounted for about 1% of hospitalizations at baseline, but made up 6% of hospitalizations by the end of the study, he said.

Dr. Myers noted that recent projections about the burden of HCV in the United States are very similar to his findings. According to a calculation model based on epidemiologic data from the U.S. Centers for Disease Control and Prevention, mortality related to HCV is likely to increase over the next 25 years (J. Viral Hepat. 2007;14:107–15). The study estimated that the number of cases has risen from about 3,700 in 1998, and will peak at about 13,000 in 2030. Similar Canadian projections have been reported.

A separate study reported at the meeting was based on a unique, province-wide data system to estimate the rate of new cases of HCV infection in British Columbia. The British Columbia Centre for Disease Control laboratory data from 1992–2005 enable the researchers to document positive HCV results in people who previously tested negative, said Margot Kuo, Ph.D., from the University of British Columbia, Vancouver. As such, it offers a unique picture of testing practices and seroconversion trends.

Her analysis identified a significantly higher incidence of newly acquired infection than had been previously reported, with the highest incidence in 20- to 29-year-olds and 30- to 39-year-olds at 13.6 and 11.3 cases per 100,000, respectively.

“The effect of gender on the rates was not consistent across all ages,” she noted. “Males had a slightly higher incidence across all age groups except teens. We were picking up HCV seroconversion among teen females four times more frequently than among teen males.” This was reflected in an incidence of 5 cases per 100,000 in teen females, compared with 1.3 cases per 100,000 in teen males.

“While this could mean that teen females are at higher risk, it's likely related to testing patterns,” she commented. “Teen males have a very low rate of testing and display very low repeat test behavior, while females tend to test more, and have more repeat tests.” Nevertheless, the finding has important implications for the development of prevention strategies, she said.

MONTREAL — The escalating numbers of new and existing hepatitis C infections in Canada are reinforcing the evidence of a U.S. epidemic, Dr. Robert P. Myers said at Canadian Digestive Diseases Week.

“The burden of hepatitis C has grown dramatically in the past decade,” said Dr. Myers of the University of Calgary (Alta). “It is vital that we continue with preventive measures and maximize treatment.”

By using an administrative hospitalization database from the Calgary Health Region, Dr. Myers identified 4,002 hospitalizations related to hepatitis C virus (HCV) infection between 1994 and 2004, 22% of which (869 cases) were HCV liver-related, he reported. Among this group of patients, 67% were male, with a median age of 50 years.

With a concentration on number of hospitalizations, length of hospital stay, and in-hospital mortality, Dr. Myers documented an approximate fourfold increase over the 11-year period. Hospital charges for this population also increased an average of 41% between 2000 and 2004, which was attributable to more admissions rather than longer hospital stays. The length of stay actually stabilized during this period, at an average of 7 days, he said.

“We project if this rate continues in a linear fashion that by 2020, across Canada, about $240 million [Canadian] will be spent on hepatitis C liver-related hospitalizations,” he said.

Patient subgroups that were identified as particularly high risk included females, who represented 25% of the hospitalizations at the beginning of the study period but increased to 35% by the end, for an average annual increase of 19%.

“Interestingly, if you compare that to the males, somewhat counterintuitively males had a lower annual growth rate in hospitalizations of 13.1%,” he said. “The etiology of that is a bit unclear, but it may perhaps be due to underreporting at the beginning of the study.” He noted that even when adjustments were made to account for underreporting, the findings remained significant.

Other high-risk groups were patients aged 40–59 years, for whom hospitalizations increased more than in any other age group, at 19% annually, and HIV-coinfected patients. The latter accounted for about 1% of hospitalizations at baseline, but made up 6% of hospitalizations by the end of the study, he said.

Dr. Myers noted that recent projections about the burden of HCV in the United States are very similar to his findings. According to a calculation model based on epidemiologic data from the U.S. Centers for Disease Control and Prevention, mortality related to HCV is likely to increase over the next 25 years (J. Viral Hepat. 2007;14:107–15). The study estimated that the number of cases has risen from about 3,700 in 1998, and will peak at about 13,000 in 2030. Similar Canadian projections have been reported.

A separate study reported at the meeting was based on a unique, province-wide data system to estimate the rate of new cases of HCV infection in British Columbia. The British Columbia Centre for Disease Control laboratory data from 1992–2005 enable the researchers to document positive HCV results in people who previously tested negative, said Margot Kuo, Ph.D., from the University of British Columbia, Vancouver. As such, it offers a unique picture of testing practices and seroconversion trends.

Her analysis identified a significantly higher incidence of newly acquired infection than had been previously reported, with the highest incidence in 20- to 29-year-olds and 30- to 39-year-olds at 13.6 and 11.3 cases per 100,000, respectively.

“The effect of gender on the rates was not consistent across all ages,” she noted. “Males had a slightly higher incidence across all age groups except teens. We were picking up HCV seroconversion among teen females four times more frequently than among teen males.” This was reflected in an incidence of 5 cases per 100,000 in teen females, compared with 1.3 cases per 100,000 in teen males.

“While this could mean that teen females are at higher risk, it's likely related to testing patterns,” she commented. “Teen males have a very low rate of testing and display very low repeat test behavior, while females tend to test more, and have more repeat tests.” Nevertheless, the finding has important implications for the development of prevention strategies, she said.

MONTREAL — The escalating numbers of new and existing hepatitis C infections in Canada are reinforcing the evidence of a U.S. epidemic, Dr. Robert P. Myers said at Canadian Digestive Diseases Week.

“The burden of hepatitis C has grown dramatically in the past decade,” said Dr. Myers of the University of Calgary (Alta). “It is vital that we continue with preventive measures and maximize treatment.”

By using an administrative hospitalization database from the Calgary Health Region, Dr. Myers identified 4,002 hospitalizations related to hepatitis C virus (HCV) infection between 1994 and 2004, 22% of which (869 cases) were HCV liver-related, he reported. Among this group of patients, 67% were male, with a median age of 50 years.

With a concentration on number of hospitalizations, length of hospital stay, and in-hospital mortality, Dr. Myers documented an approximate fourfold increase over the 11-year period. Hospital charges for this population also increased an average of 41% between 2000 and 2004, which was attributable to more admissions rather than longer hospital stays. The length of stay actually stabilized during this period, at an average of 7 days, he said.

“We project if this rate continues in a linear fashion that by 2020, across Canada, about $240 million [Canadian] will be spent on hepatitis C liver-related hospitalizations,” he said.

Patient subgroups that were identified as particularly high risk included females, who represented 25% of the hospitalizations at the beginning of the study period but increased to 35% by the end, for an average annual increase of 19%.

“Interestingly, if you compare that to the males, somewhat counterintuitively males had a lower annual growth rate in hospitalizations of 13.1%,” he said. “The etiology of that is a bit unclear, but it may perhaps be due to underreporting at the beginning of the study.” He noted that even when adjustments were made to account for underreporting, the findings remained significant.

Other high-risk groups were patients aged 40–59 years, for whom hospitalizations increased more than in any other age group, at 19% annually, and HIV-coinfected patients. The latter accounted for about 1% of hospitalizations at baseline, but made up 6% of hospitalizations by the end of the study, he said.

Dr. Myers noted that recent projections about the burden of HCV in the United States are very similar to his findings. According to a calculation model based on epidemiologic data from the U.S. Centers for Disease Control and Prevention, mortality related to HCV is likely to increase over the next 25 years (J. Viral Hepat. 2007;14:107–15). The study estimated that the number of cases has risen from about 3,700 in 1998, and will peak at about 13,000 in 2030. Similar Canadian projections have been reported.

A separate study reported at the meeting was based on a unique, province-wide data system to estimate the rate of new cases of HCV infection in British Columbia. The British Columbia Centre for Disease Control laboratory data from 1992–2005 enable the researchers to document positive HCV results in people who previously tested negative, said Margot Kuo, Ph.D., from the University of British Columbia, Vancouver. As such, it offers a unique picture of testing practices and seroconversion trends.

Her analysis identified a significantly higher incidence of newly acquired infection than had been previously reported, with the highest incidence in 20- to 29-year-olds and 30- to 39-year-olds at 13.6 and 11.3 cases per 100,000, respectively.

“The effect of gender on the rates was not consistent across all ages,” she noted. “Males had a slightly higher incidence across all age groups except teens. We were picking up HCV seroconversion among teen females four times more frequently than among teen males.” This was reflected in an incidence of 5 cases per 100,000 in teen females, compared with 1.3 cases per 100,000 in teen males.

“While this could mean that teen females are at higher risk, it's likely related to testing patterns,” she commented. “Teen males have a very low rate of testing and display very low repeat test behavior, while females tend to test more, and have more repeat tests.” Nevertheless, the finding has important implications for the development of prevention strategies, she said.

MONTREAL — Primary care physicians referring patients for routine colorectal cancer screening may see better adherence, particularly in men, if they consider patient preference regarding screening modality, reported Maida Sewitch, Ph.D., from McGill University, Montreal. However, the picture is less clear for women.

In a study of 203 primary care patients referred for colorectal cancer screening (40% male and 60% female, mean age 64 years), overall adherence was 52%, Dr. Sewitch reported in a poster at Canadian Digestive Diseases Week.

For both genders combined, the strongest predictor of adherence was a physician's referral that matched a patient's preferred screening modality (adjusted odds ratio 3.64), she said. But the results looked quite different when analyzed according to patient gender.

“The people for whom matched modality was important were the men—and men who were matched on modality were 3.5 times more likely to adhere to screening referral than men who were not matched. But women didn't care about modality. We didn't expect that at all,” Dr. Sewitch said in an interview.

The four choices of screening modality in the study were colonoscopy, double contrast barium enema, flexible sigmoidoscopy, and fecal occult blood testing (FOBT). The most commonly requested modality was FOBT, she said.

Although matching the referral modality to patient preference increased the odds of screening adherence in men (AOR 3.49), it only had a slight impact in women (AOR 1.24), she said. Instead, predictors of female adherence to screening were past history of screening (AOR 2.1), she reported.

“Women may have more trust in their physician's recommendation, and a past history of screening may demystify the experience, whereas men want what they want,” she said. “It might have a lot to do with control. Physicians should be speaking with patients about what they want. If they're going to recommend some kind of colorectal cancer screening, they can ask their patients what they want to do and give their referral based on that.”

A second poster presented at the meeting described an investigation of patient preference regarding the timing of a precolonoscopy consult with a gastroenterologist. A total of 125 average-risk patients (66% male, mean age 60 years) participated in the study, with 21% receiving a gastroenterology consult on a different day (DD) prior to their colonoscopy, and 79% receiving the consult on the same day (SD), just before their colonoscopy.

Patients were asked to complete a questionnaire after their colonoscopy regarding their preference for a DD or SD consult, reported Dr. Liliana Oliveira from the University of Ottawa. The study found that patient preferences appeared to be affected only by patients' previous consultation experience. In patients who had an SD consult, 86% indicated a preference for this practice, and in those who had a DD consult, 61.5% preferred this practice; these findings were significant.

The authors concluded that SD consultation is a practice that is acceptable to patients. “[Most] preferred it because it saved time and they already had all the information from their family doctor,” said Dr. Oliveira in an interview. “So the more information the patients can get from the family doctors, the better.”

She stressed that same-day consultation is only intended for average-risk patients. “It's not for people who have a family history of colon cancer or medical problems—it's for the routine patients.” Although same-day consultation is common, she said it remains somewhat controversial for several reasons, and patient preference had not been measured previously.

MONTREAL — Primary care physicians referring patients for routine colorectal cancer screening may see better adherence, particularly in men, if they consider patient preference regarding screening modality, reported Maida Sewitch, Ph.D., from McGill University, Montreal. However, the picture is less clear for women.

In a study of 203 primary care patients referred for colorectal cancer screening (40% male and 60% female, mean age 64 years), overall adherence was 52%, Dr. Sewitch reported in a poster at Canadian Digestive Diseases Week.

For both genders combined, the strongest predictor of adherence was a physician's referral that matched a patient's preferred screening modality (adjusted odds ratio 3.64), she said. But the results looked quite different when analyzed according to patient gender.

“The people for whom matched modality was important were the men—and men who were matched on modality were 3.5 times more likely to adhere to screening referral than men who were not matched. But women didn't care about modality. We didn't expect that at all,” Dr. Sewitch said in an interview.

The four choices of screening modality in the study were colonoscopy, double contrast barium enema, flexible sigmoidoscopy, and fecal occult blood testing (FOBT). The most commonly requested modality was FOBT, she said.

Although matching the referral modality to patient preference increased the odds of screening adherence in men (AOR 3.49), it only had a slight impact in women (AOR 1.24), she said. Instead, predictors of female adherence to screening were past history of screening (AOR 2.1), she reported.

“Women may have more trust in their physician's recommendation, and a past history of screening may demystify the experience, whereas men want what they want,” she said. “It might have a lot to do with control. Physicians should be speaking with patients about what they want. If they're going to recommend some kind of colorectal cancer screening, they can ask their patients what they want to do and give their referral based on that.”

A second poster presented at the meeting described an investigation of patient preference regarding the timing of a precolonoscopy consult with a gastroenterologist. A total of 125 average-risk patients (66% male, mean age 60 years) participated in the study, with 21% receiving a gastroenterology consult on a different day (DD) prior to their colonoscopy, and 79% receiving the consult on the same day (SD), just before their colonoscopy.

Patients were asked to complete a questionnaire after their colonoscopy regarding their preference for a DD or SD consult, reported Dr. Liliana Oliveira from the University of Ottawa. The study found that patient preferences appeared to be affected only by patients' previous consultation experience. In patients who had an SD consult, 86% indicated a preference for this practice, and in those who had a DD consult, 61.5% preferred this practice; these findings were significant.

The authors concluded that SD consultation is a practice that is acceptable to patients. “[Most] preferred it because it saved time and they already had all the information from their family doctor,” said Dr. Oliveira in an interview. “So the more information the patients can get from the family doctors, the better.”

She stressed that same-day consultation is only intended for average-risk patients. “It's not for people who have a family history of colon cancer or medical problems—it's for the routine patients.” Although same-day consultation is common, she said it remains somewhat controversial for several reasons, and patient preference had not been measured previously.

MONTREAL — Primary care physicians referring patients for routine colorectal cancer screening may see better adherence, particularly in men, if they consider patient preference regarding screening modality, reported Maida Sewitch, Ph.D., from McGill University, Montreal. However, the picture is less clear for women.

In a study of 203 primary care patients referred for colorectal cancer screening (40% male and 60% female, mean age 64 years), overall adherence was 52%, Dr. Sewitch reported in a poster at Canadian Digestive Diseases Week.

For both genders combined, the strongest predictor of adherence was a physician's referral that matched a patient's preferred screening modality (adjusted odds ratio 3.64), she said. But the results looked quite different when analyzed according to patient gender.

“The people for whom matched modality was important were the men—and men who were matched on modality were 3.5 times more likely to adhere to screening referral than men who were not matched. But women didn't care about modality. We didn't expect that at all,” Dr. Sewitch said in an interview.

The four choices of screening modality in the study were colonoscopy, double contrast barium enema, flexible sigmoidoscopy, and fecal occult blood testing (FOBT). The most commonly requested modality was FOBT, she said.

Although matching the referral modality to patient preference increased the odds of screening adherence in men (AOR 3.49), it only had a slight impact in women (AOR 1.24), she said. Instead, predictors of female adherence to screening were past history of screening (AOR 2.1), she reported.

“Women may have more trust in their physician's recommendation, and a past history of screening may demystify the experience, whereas men want what they want,” she said. “It might have a lot to do with control. Physicians should be speaking with patients about what they want. If they're going to recommend some kind of colorectal cancer screening, they can ask their patients what they want to do and give their referral based on that.”

A second poster presented at the meeting described an investigation of patient preference regarding the timing of a precolonoscopy consult with a gastroenterologist. A total of 125 average-risk patients (66% male, mean age 60 years) participated in the study, with 21% receiving a gastroenterology consult on a different day (DD) prior to their colonoscopy, and 79% receiving the consult on the same day (SD), just before their colonoscopy.

Patients were asked to complete a questionnaire after their colonoscopy regarding their preference for a DD or SD consult, reported Dr. Liliana Oliveira from the University of Ottawa. The study found that patient preferences appeared to be affected only by patients' previous consultation experience. In patients who had an SD consult, 86% indicated a preference for this practice, and in those who had a DD consult, 61.5% preferred this practice; these findings were significant.

The authors concluded that SD consultation is a practice that is acceptable to patients. “[Most] preferred it because it saved time and they already had all the information from their family doctor,” said Dr. Oliveira in an interview. “So the more information the patients can get from the family doctors, the better.”

She stressed that same-day consultation is only intended for average-risk patients. “It's not for people who have a family history of colon cancer or medical problems—it's for the routine patients.” Although same-day consultation is common, she said it remains somewhat controversial for several reasons, and patient preference had not been measured previously.

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” she said in an interview, describing the possibility that patients' early symptoms of pneumonia might mimic gastroesophageal reflux and prompt a prescription for a proton pump inhibitor (PPI). “Then they go on to develop obvious pneumonia, but the PPI actually played no role in it,” said Dr. Targownik of the University of Manitoba, Winnipeg.

Recent studies have described the increased risk of infections such as community-acquired pneumonia and Clostridium difficile associated with PPI use, she explained. While the mechanism for this association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik's study analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating,” adding that further research is being done to disentangle the effect of gastroesophageal reflux in the data.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” she said in an interview, describing the possibility that patients' early symptoms of pneumonia might mimic gastroesophageal reflux and prompt a prescription for a proton pump inhibitor (PPI). “Then they go on to develop obvious pneumonia, but the PPI actually played no role in it,” said Dr. Targownik of the University of Manitoba, Winnipeg.

Recent studies have described the increased risk of infections such as community-acquired pneumonia and Clostridium difficile associated with PPI use, she explained. While the mechanism for this association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik's study analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating,” adding that further research is being done to disentangle the effect of gastroesophageal reflux in the data.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” she said in an interview, describing the possibility that patients' early symptoms of pneumonia might mimic gastroesophageal reflux and prompt a prescription for a proton pump inhibitor (PPI). “Then they go on to develop obvious pneumonia, but the PPI actually played no role in it,” said Dr. Targownik of the University of Manitoba, Winnipeg.

Recent studies have described the increased risk of infections such as community-acquired pneumonia and Clostridium difficile associated with PPI use, she explained. While the mechanism for this association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik's study analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating,” adding that further research is being done to disentangle the effect of gastroesophageal reflux in the data.

The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were two cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.

The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% of them were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” Dr. Williams explained at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16–78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male; 74% presented with dysphagia and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, Dr. Williams said.

In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Dr. Williams noted that overall this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” Dr. Williams said, adding that he recommends medical treatment with fluticasone as the first-line therapy.

Eosinophilic esophagitis (shown on endoscopy) is being detected more often. Courtesy Dr. Chad Williams

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were two cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.

The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% of them were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” Dr. Williams explained at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16–78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male; 74% presented with dysphagia and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, Dr. Williams said.

In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Dr. Williams noted that overall this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” Dr. Williams said, adding that he recommends medical treatment with fluticasone as the first-line therapy.

Eosinophilic esophagitis (shown on endoscopy) is being detected more often. Courtesy Dr. Chad Williams

MONTREAL — The incidence of adult and pediatric eosinophilic esophagitis appears to be increasing dramatically, and endoscopic investigation and treatment have low complication rates, according to the findings of the largest reported population-based study of the disorder.

Dr. Chad Williams and his colleagues from the University of Calgary (Alta.) found an incidence of 7.2 cases/100,000 person-years in 2006 in the Calgary Health Region (population 1.2 million), the highest incidence to date, they reported in a poster at the Canadian Digestive Diseases Week.

“The number of diagnoses per year is definitely rising,” Dr. Williams said in an interview. “Whether that reflects a true increase in incidence we're not sure. We may be just recognizing it more.”

Few studies have investigated the incidence of eosinophilic esophagitis in general, and none has addressed the incidence in the adult North American population in particular, he said. A European study reported an adult incidence of 6 cases/100,000 person-years (J. Allergy Clin. Immunol. 2005;115:418–9).

In their retrospective cohort study, Dr. Williams and his colleagues identified adult and pediatric biopsy-proven cases of eosinophilic esophagitis in the Calgary Health Region between 2002 and 2006. Overall, there were two cases identified in 2002, and no cases in 2003. However, the reported incidence rose dramatically from 1.83 cases/100,000 person-years in 2004 to 4.27 cases in 2005 and to 7.2 cases in 2006.

The incidence per 1,000 upper endoscopies rose from 2.16 cases in 2004 to 8.35 cases in 2006.

The incidence seemed to increase in adults, while it dipped among children. The number of cases in adults went from 5 in 2004 to 75 in 2006, compared with 16 in 2004 to 6 in 2006 in children.

Among the total of 158 identified cases, 75% of them were adults and 84% were male. The median age of adult patients was 39 years, and the median pediatric age was 12 years.

“In the pediatric population, patients usually present with food aversion, gastroesophageal refluxlike symptoms and abdominal pain, but in the adult population, the two main symptoms are dysphagia and food bolus impaction,” Dr. Williams explained at the conference, which was sponsored by the Canadian Association of Gastroenterology.

In a subanalysis of 144 of the eosinophilic esophagitis cases, the mean age of the patient population was 40 years (range 16–78 years), Dr. Williams' group reported in another poster.

Most (85%) of the patients were male; 74% presented with dysphagia and 18% with food impaction. Allergies were noted in 27% of patients, asthma in 22%, gastroesophageal reflux disease in about 20%, and autoimmune disease in about 3%. All of the patients underwent endoscopic evaluation and biopsy, with 22% of patients also receiving concurrent therapeutic esophageal dilation.

Endoscopic complications were more common in patients undergoing dilation, with six mucosal tears documented, but no perforations, Dr. Williams said.

In patients undergoing endoscopic biopsy alone, there was one mucosal tear resulting from the biopsy, and one resulting from trauma from the endoscope. Dr. Williams noted that overall this complication rate was low, compared with a previously reported rate of 30% (Clin. Gastroenterol. Hepatol. 2007;5:1149–53).

“Gastroscopy is a fairly safe procedure, although we did have one mucosal tear in our group, but I am not a proponent of dilation in this population,” Dr. Williams said, adding that he recommends medical treatment with fluticasone as the first-line therapy.

Eosinophilic esophagitis (shown on endoscopy) is being detected more often. Courtesy Dr. Chad Williams

Caffeine adversely affects glucose metabolism in diabetic patients by exaggerating postprandial glucose responses, which leads to higher daytime glucose concentrations, according to a report in Diabetes Care.

“The presence of hyperglycemic effects in these free-living individuals raises concerns about the potential hazards of caffeinated beverages for patients with type 2 diabetes,” wrote James D. Lane, Ph.D., and colleagues from Duke University Medical Center in Durham, N.C. (Diabetes Care 2008;31:1-2).

In a double-blind crossover study, the researchers compared the effects of a moderate dose of caffeine (500 mg/day, roughly equivalent to four 8-ounce cups of brewed coffee) with placebo on glucose levels in 10 diabetic patients.

The patients (five men and five women, mean age, 63 years) were all habitual coffee drinkers with a mean self-reported daily intake of 520 mg/day, based on a conversion of beverage consumption using standard caffeine content measurements.

All had at least a 6-month history of type 2 diabetes managed by diet, exercise, and oral agents, but no exogenous insulin.

The subjects abstained from their daily coffee during the two 24-hour study days, and caffeine and placebo treatments were administered in identical gelatin capsules on different study days.

Ambulatory glucose concentration was assessed with continuous glucose monitoring over 72 hours, with planned analyses focusing on daytime glucose levels (when caffeine was at pharmacologically active concentrations) and postprandial responses, noted the authors.

Subjects consumed two capsules (total 250 mg) of either caffeine or placebo at breakfast and again at lunch. A standardized breakfast was consumed, whereas lunch and dinner were ingested “ad libitum.”

Subjects recorded the times of each meal so that postprandial glucose response could be assessed.

The analysis revealed that, compared with placebo, average daytime glucose levels increased in response to caffeine (8.0 vs. 7.4 mmol/L). Average postprandial glucose responses were also found to be elevated after caffeine consumption (8.7 vs. 8.0 mmol/L after breakfast, 7.8 vs. 6.8 mmol/L after lunch, and 8.6 vs. 6.8 mmol/L after dinner).

“Caffeine exposure may have reduced overnight glucose compared to placebo (caffeine abstinence). This possibility will be the subject of future studies,” wrote the authors. “Repeated episodes of elevated glucose resulting from daily consumption of caffeinated beverages could impair clinical efforts aimed at glucose control and increase risk of diabetes complications.”

The authors did not list any conflicts of interest related to the study.

Caffeine adversely affects glucose metabolism in diabetic patients by exaggerating postprandial glucose responses, which leads to higher daytime glucose concentrations, according to a report in Diabetes Care.

“The presence of hyperglycemic effects in these free-living individuals raises concerns about the potential hazards of caffeinated beverages for patients with type 2 diabetes,” wrote James D. Lane, Ph.D., and colleagues from Duke University Medical Center in Durham, N.C. (Diabetes Care 2008;31:1-2).

In a double-blind crossover study, the researchers compared the effects of a moderate dose of caffeine (500 mg/day, roughly equivalent to four 8-ounce cups of brewed coffee) with placebo on glucose levels in 10 diabetic patients.

The patients (five men and five women, mean age, 63 years) were all habitual coffee drinkers with a mean self-reported daily intake of 520 mg/day, based on a conversion of beverage consumption using standard caffeine content measurements.

All had at least a 6-month history of type 2 diabetes managed by diet, exercise, and oral agents, but no exogenous insulin.

The subjects abstained from their daily coffee during the two 24-hour study days, and caffeine and placebo treatments were administered in identical gelatin capsules on different study days.

Ambulatory glucose concentration was assessed with continuous glucose monitoring over 72 hours, with planned analyses focusing on daytime glucose levels (when caffeine was at pharmacologically active concentrations) and postprandial responses, noted the authors.

Subjects consumed two capsules (total 250 mg) of either caffeine or placebo at breakfast and again at lunch. A standardized breakfast was consumed, whereas lunch and dinner were ingested “ad libitum.”

Subjects recorded the times of each meal so that postprandial glucose response could be assessed.

The analysis revealed that, compared with placebo, average daytime glucose levels increased in response to caffeine (8.0 vs. 7.4 mmol/L). Average postprandial glucose responses were also found to be elevated after caffeine consumption (8.7 vs. 8.0 mmol/L after breakfast, 7.8 vs. 6.8 mmol/L after lunch, and 8.6 vs. 6.8 mmol/L after dinner).

“Caffeine exposure may have reduced overnight glucose compared to placebo (caffeine abstinence). This possibility will be the subject of future studies,” wrote the authors. “Repeated episodes of elevated glucose resulting from daily consumption of caffeinated beverages could impair clinical efforts aimed at glucose control and increase risk of diabetes complications.”

The authors did not list any conflicts of interest related to the study.

Caffeine adversely affects glucose metabolism in diabetic patients by exaggerating postprandial glucose responses, which leads to higher daytime glucose concentrations, according to a report in Diabetes Care.

“The presence of hyperglycemic effects in these free-living individuals raises concerns about the potential hazards of caffeinated beverages for patients with type 2 diabetes,” wrote James D. Lane, Ph.D., and colleagues from Duke University Medical Center in Durham, N.C. (Diabetes Care 2008;31:1-2).

In a double-blind crossover study, the researchers compared the effects of a moderate dose of caffeine (500 mg/day, roughly equivalent to four 8-ounce cups of brewed coffee) with placebo on glucose levels in 10 diabetic patients.

The patients (five men and five women, mean age, 63 years) were all habitual coffee drinkers with a mean self-reported daily intake of 520 mg/day, based on a conversion of beverage consumption using standard caffeine content measurements.

All had at least a 6-month history of type 2 diabetes managed by diet, exercise, and oral agents, but no exogenous insulin.

The subjects abstained from their daily coffee during the two 24-hour study days, and caffeine and placebo treatments were administered in identical gelatin capsules on different study days.

Ambulatory glucose concentration was assessed with continuous glucose monitoring over 72 hours, with planned analyses focusing on daytime glucose levels (when caffeine was at pharmacologically active concentrations) and postprandial responses, noted the authors.

Subjects consumed two capsules (total 250 mg) of either caffeine or placebo at breakfast and again at lunch. A standardized breakfast was consumed, whereas lunch and dinner were ingested “ad libitum.”

Subjects recorded the times of each meal so that postprandial glucose response could be assessed.

The analysis revealed that, compared with placebo, average daytime glucose levels increased in response to caffeine (8.0 vs. 7.4 mmol/L). Average postprandial glucose responses were also found to be elevated after caffeine consumption (8.7 vs. 8.0 mmol/L after breakfast, 7.8 vs. 6.8 mmol/L after lunch, and 8.6 vs. 6.8 mmol/L after dinner).

“Caffeine exposure may have reduced overnight glucose compared to placebo (caffeine abstinence). This possibility will be the subject of future studies,” wrote the authors. “Repeated episodes of elevated glucose resulting from daily consumption of caffeinated beverages could impair clinical efforts aimed at glucose control and increase risk of diabetes complications.”

The authors did not list any conflicts of interest related to the study.

Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

ELSEVIER GLOBAL MEDICAL NEWS

Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

ELSEVIER GLOBAL MEDICAL NEWS

Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

ELSEVIER GLOBAL MEDICAL NEWS

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” asked Dr. Targownik of the University of Manitoba, Winnipeg.

While a mechanism for an association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating.” The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” asked Dr. Targownik of the University of Manitoba, Winnipeg.

While a mechanism for an association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating.” The meeting was sponsored by the Canadian Association of Gastroenterology.

MONTREAL — The association of proton pump inhibitors with an increased risk of severe respiratory infections is dramatically pronounced in the first 2 weeks of drug therapy, according to a new study.

However, the reasons for this particularly high risk are not clear, Dr. Laura Targownik said at Canadian Digestive Diseases Week. “I reported the data because they are very dramatic, but the question remains, is it a protopathic effect?” asked Dr. Targownik of the University of Manitoba, Winnipeg.

While a mechanism for an association is not known, the most common hypothesis suggests that PPIs' reduction of gastric acid allows gastric pathogens to flourish and, via reflux, infect either the gastrointestinal tract or the lungs.

Dr. Targownik analyzed 1,276 cases of severe community-acquired infections identified in the Manitoba Health Database between 1996 and 2004. All cases were matched to up to 10 controls with no history of serious infections on the index date.

For 296 cases of urinary tract infection and 289 cases of gastrointestinal infection, Dr. Targownik found no increased risk associated with PPI therapy. However, PPI use was associated with an increased risk of severe respiratory infection or pneumonia (adjusted odds ratio [AOR] 1.35), she reported. And a subanalysis of 62 patients with respiratory infection and PPI use found that the risk of respiratory infection was most pronounced within 14 days of PPI initiation, compared with cases in which PPIs were started earlier (AOR 24.5 vs. 1.12).

The findings suggest that “you may be inducing some bacterial changes that [initially] increase the risk,” Dr. Targownik explained, before the body subsequently adjusts. She described her findings as “hypothesis generating.” The meeting was sponsored by the Canadian Association of Gastroenterology.