Colin Nelson

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

BOSTON — Doctors continue to prescribe the antidepressant amitriptyline for treatment of diabetic peripheral neuropathy in the elderly despite advisories that discourage its use in this population, according to study findings reported at the annual meeting of the American Pain Society.

“Amitriptyline has been studied for a long time in diabetic neuropathy, so we were not surprised it's used,” said lead author Ariel Berger, MPH, of Policy Analysis Inc., Brookline, Mass., in an interview. “What was surprising to us was that nearly half of patients had evidence of potentially inappropriate prescribing. [Physicians] had red alerts, prior to beginning therapy, but they prescribed them anyway.”

Mr. Berger and his associates at Pfizer Inc. and Oregon Health and Science University, Portland, identified all patients in a large health-claims database who were diagnosed with diabetic peripheral neuropathy, were aged 65 years or older, and had received a prescription for a tricyclic antidepressant (TCA).

The researchers documented which specific TCAs the patients received, their average daily dose, and the number of medication refills. Finally, they documented specific contraindications, warnings, and precautions listed on the TCA package inserts and compared these with the patients' medical records.

A total of 296 elderly patients received a prescription for a TCA. Nearly half (45.3%) had a diagnosis (cardiovascular disease) or concurrent prescription (thyroid medication) listed among the contraindications, warnings, or precautions in TCA product labeling.

Eight out of 10 who received TCAs received amitriptyline, considered by many to pose the most risk for patients over age 65 years.

Guidelines for the treatment of older patients advise physicians that TCAs in general—and amitriptyline in particular—are potentially dangerous in the elderly. In 1999, the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services) recommended the use of nortriptyline in its place.

The package insert for amitriptyline advises doctors to carefully monitor patients with cardiovascular disorders and notes that the medication can cause cardiac arrhythmias, sinus tachycardia, myocardial infarction, and stroke, as well as both elevated and depressed blood sugar levels.

Pfizer, the study sponsor, has received FDA approval to market the anticonvulsant pregabalin for treatment of diabetic peripheral neuropathy.

BOSTON — Doctors continue to prescribe the antidepressant amitriptyline for treatment of diabetic peripheral neuropathy in the elderly despite advisories that discourage its use in this population, according to study findings reported at the annual meeting of the American Pain Society.

“Amitriptyline has been studied for a long time in diabetic neuropathy, so we were not surprised it's used,” said lead author Ariel Berger, MPH, of Policy Analysis Inc., Brookline, Mass., in an interview. “What was surprising to us was that nearly half of patients had evidence of potentially inappropriate prescribing. [Physicians] had red alerts, prior to beginning therapy, but they prescribed them anyway.”

Mr. Berger and his associates at Pfizer Inc. and Oregon Health and Science University, Portland, identified all patients in a large health-claims database who were diagnosed with diabetic peripheral neuropathy, were aged 65 years or older, and had received a prescription for a tricyclic antidepressant (TCA).

The researchers documented which specific TCAs the patients received, their average daily dose, and the number of medication refills. Finally, they documented specific contraindications, warnings, and precautions listed on the TCA package inserts and compared these with the patients' medical records.

A total of 296 elderly patients received a prescription for a TCA. Nearly half (45.3%) had a diagnosis (cardiovascular disease) or concurrent prescription (thyroid medication) listed among the contraindications, warnings, or precautions in TCA product labeling.

Eight out of 10 who received TCAs received amitriptyline, considered by many to pose the most risk for patients over age 65 years.

Guidelines for the treatment of older patients advise physicians that TCAs in general—and amitriptyline in particular—are potentially dangerous in the elderly. In 1999, the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services) recommended the use of nortriptyline in its place.

The package insert for amitriptyline advises doctors to carefully monitor patients with cardiovascular disorders and notes that the medication can cause cardiac arrhythmias, sinus tachycardia, myocardial infarction, and stroke, as well as both elevated and depressed blood sugar levels.

Pfizer, the study sponsor, has received FDA approval to market the anticonvulsant pregabalin for treatment of diabetic peripheral neuropathy.

BOSTON — Doctors continue to prescribe the antidepressant amitriptyline for treatment of diabetic peripheral neuropathy in the elderly despite advisories that discourage its use in this population, according to study findings reported at the annual meeting of the American Pain Society.

“Amitriptyline has been studied for a long time in diabetic neuropathy, so we were not surprised it's used,” said lead author Ariel Berger, MPH, of Policy Analysis Inc., Brookline, Mass., in an interview. “What was surprising to us was that nearly half of patients had evidence of potentially inappropriate prescribing. [Physicians] had red alerts, prior to beginning therapy, but they prescribed them anyway.”

Mr. Berger and his associates at Pfizer Inc. and Oregon Health and Science University, Portland, identified all patients in a large health-claims database who were diagnosed with diabetic peripheral neuropathy, were aged 65 years or older, and had received a prescription for a tricyclic antidepressant (TCA).

The researchers documented which specific TCAs the patients received, their average daily dose, and the number of medication refills. Finally, they documented specific contraindications, warnings, and precautions listed on the TCA package inserts and compared these with the patients' medical records.

A total of 296 elderly patients received a prescription for a TCA. Nearly half (45.3%) had a diagnosis (cardiovascular disease) or concurrent prescription (thyroid medication) listed among the contraindications, warnings, or precautions in TCA product labeling.

Eight out of 10 who received TCAs received amitriptyline, considered by many to pose the most risk for patients over age 65 years.

Guidelines for the treatment of older patients advise physicians that TCAs in general—and amitriptyline in particular—are potentially dangerous in the elderly. In 1999, the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services) recommended the use of nortriptyline in its place.

The package insert for amitriptyline advises doctors to carefully monitor patients with cardiovascular disorders and notes that the medication can cause cardiac arrhythmias, sinus tachycardia, myocardial infarction, and stroke, as well as both elevated and depressed blood sugar levels.

Pfizer, the study sponsor, has received FDA approval to market the anticonvulsant pregabalin for treatment of diabetic peripheral neuropathy.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

BOSTON – A test measuring somatization can predict which patients with chronic headaches will benefit from outpatient care and which ones won't–and will instead require intensive inpatient therapy, according to a new study.

The next step is to explore whether it is possible to calculate an exact cutoff score that would signal which patients should skip outpatient care and go directly to inpatient therapy, Dana Brendza, Psy.D., and associates suggested in a poster presented at the annual meeting of the American Pain Society.

Dr. Brendza and associates at the Cleveland Clinic studied the medical records of 213 patients enrolled in the multidisciplinary treatment program of an outpatient neurology headache clinic. Neurologists had referred the patients, predominantly white women aged 17–85, for psychological evaluation. All patients filled out the 344-item Personality Assessment Inventory (PAI), a tool used for assessing personality and psychopathology.

As a group, the patients' scores on the Somatic Complaints subscale were significantly elevated (two standard deviations above normal). Individually, the scores of more than half (51.6%) were considered clinically elevated.

The researchers took a closer look at the patients who failed outpatient treatment and required referral to the inpatient pain program. Their scores on the Somatic Complaints scale were significantly higher than the scores of patients who did not fail outpatient therapy.

Elevated scores on another measure (the Physical Symptoms subscale of the Depression scale) showed they were also more likely to be tuned in to physical symptoms.

The findings are consistent with a common belief among chronic headache patients that their malady is rooted in physical causes, not primarily psychological ones, coauthor Kathleen Ashton, Ph.D., explained in an interview.

The results also reinforce previous research suggesting that disability is often more intractable in headache patients who suffer from anxiety and mood disorders.

“The PAI Somatic Complaints scale may be useful in identifying patients who are most likely to be referred to an intensive, inpatient chronic pain treatment program after failure to improve in traditional outpatient treatment for their headache disorders,” the researchers concluded.

In patients with high scores, “there is probably an underlying emotional component to this pain that's not being addressed in outpatient therapy,” Dr. Ashton suggested. In addition, headache patients scoring lower on the Somatic Complaints scale are probably more amenable to psychological therapy, she said.

BOSTON – A test measuring somatization can predict which patients with chronic headaches will benefit from outpatient care and which ones won't–and will instead require intensive inpatient therapy, according to a new study.

The next step is to explore whether it is possible to calculate an exact cutoff score that would signal which patients should skip outpatient care and go directly to inpatient therapy, Dana Brendza, Psy.D., and associates suggested in a poster presented at the annual meeting of the American Pain Society.

Dr. Brendza and associates at the Cleveland Clinic studied the medical records of 213 patients enrolled in the multidisciplinary treatment program of an outpatient neurology headache clinic. Neurologists had referred the patients, predominantly white women aged 17–85, for psychological evaluation. All patients filled out the 344-item Personality Assessment Inventory (PAI), a tool used for assessing personality and psychopathology.

As a group, the patients' scores on the Somatic Complaints subscale were significantly elevated (two standard deviations above normal). Individually, the scores of more than half (51.6%) were considered clinically elevated.

The researchers took a closer look at the patients who failed outpatient treatment and required referral to the inpatient pain program. Their scores on the Somatic Complaints scale were significantly higher than the scores of patients who did not fail outpatient therapy.

Elevated scores on another measure (the Physical Symptoms subscale of the Depression scale) showed they were also more likely to be tuned in to physical symptoms.

The findings are consistent with a common belief among chronic headache patients that their malady is rooted in physical causes, not primarily psychological ones, coauthor Kathleen Ashton, Ph.D., explained in an interview.

The results also reinforce previous research suggesting that disability is often more intractable in headache patients who suffer from anxiety and mood disorders.

“The PAI Somatic Complaints scale may be useful in identifying patients who are most likely to be referred to an intensive, inpatient chronic pain treatment program after failure to improve in traditional outpatient treatment for their headache disorders,” the researchers concluded.

In patients with high scores, “there is probably an underlying emotional component to this pain that's not being addressed in outpatient therapy,” Dr. Ashton suggested. In addition, headache patients scoring lower on the Somatic Complaints scale are probably more amenable to psychological therapy, she said.

BOSTON – A test measuring somatization can predict which patients with chronic headaches will benefit from outpatient care and which ones won't–and will instead require intensive inpatient therapy, according to a new study.

The next step is to explore whether it is possible to calculate an exact cutoff score that would signal which patients should skip outpatient care and go directly to inpatient therapy, Dana Brendza, Psy.D., and associates suggested in a poster presented at the annual meeting of the American Pain Society.

Dr. Brendza and associates at the Cleveland Clinic studied the medical records of 213 patients enrolled in the multidisciplinary treatment program of an outpatient neurology headache clinic. Neurologists had referred the patients, predominantly white women aged 17–85, for psychological evaluation. All patients filled out the 344-item Personality Assessment Inventory (PAI), a tool used for assessing personality and psychopathology.

As a group, the patients' scores on the Somatic Complaints subscale were significantly elevated (two standard deviations above normal). Individually, the scores of more than half (51.6%) were considered clinically elevated.

The researchers took a closer look at the patients who failed outpatient treatment and required referral to the inpatient pain program. Their scores on the Somatic Complaints scale were significantly higher than the scores of patients who did not fail outpatient therapy.

Elevated scores on another measure (the Physical Symptoms subscale of the Depression scale) showed they were also more likely to be tuned in to physical symptoms.

The findings are consistent with a common belief among chronic headache patients that their malady is rooted in physical causes, not primarily psychological ones, coauthor Kathleen Ashton, Ph.D., explained in an interview.

The results also reinforce previous research suggesting that disability is often more intractable in headache patients who suffer from anxiety and mood disorders.

“The PAI Somatic Complaints scale may be useful in identifying patients who are most likely to be referred to an intensive, inpatient chronic pain treatment program after failure to improve in traditional outpatient treatment for their headache disorders,” the researchers concluded.

In patients with high scores, “there is probably an underlying emotional component to this pain that's not being addressed in outpatient therapy,” Dr. Ashton suggested. In addition, headache patients scoring lower on the Somatic Complaints scale are probably more amenable to psychological therapy, she said.

BOSTON — Chronic pain was the most frequent complaint among U.S. soldiers returning from foreign war zones, according to findings from a new survey of patients at a Florida veterans' hospital.

The high prevalence and severity of chronic pain syndromes among veterans may result from stress and hardship rather than wounds, according to a report presented in a poster at the annual meeting of the American Pain Society.

Ronald Gironda, Ph.D., and his associates at the James A. Haley Veterans Affairs Medical Center in Tampa, Fla., reviewed records of 793 patients who were veterans of conflicts in Afghanistan and Iraq through November 2004.

None of the patients suffered gunshot wounds or blast injuries, he said.

About 47% of patients (373) reported pain. Some 28% (222 patients) reported pain scores of 4 or greater on a scale of 0–10. The researchers randomly selected 100 patient records from this group for closer inspection.

In the subgroup with significant pain, the average pain score was 6.6—considered “significant pain that is likely to interfere with functional activity,” said Dr. Gironda, a pain specialist.

The veterans' primary complaints were back pain (46%), lower limb pain (31%), upper limb pain (7.5%), neck pain (6%), and headache (4.5%).

“I think when all is said and done we're going to see even higher rates of pain in this new group of veterans than we saw in the Persian Gulf War,” Dr. Gironda told FAMILY PRACTICE NEWS.

The pain patients suffered a gauntlet of assaults on their well-being. Many had become physically inactive and deconditioned since their return. “They were often depressed, demoralized, unemployed, and had no social contact,” he noted.

“We know that there is a relationship between psychosocial factors and the report of pain—how it is experienced and how it develops and unfolds over time,” Dr. Gironda said. “One of the main goals of treatment is to help these individuals develop skills to cope with the pain.”

In addition to providing medical therapy, a 3-week interdisciplinary pain program introduces veterans to new exercise regimens, relaxation techniques, and cognitive-behavioral therapy to reduce fear of pain and fear of activity. Within the first week or so they also are weaned off of opiates.

“The VA has a real opportunity here,” Dr. Gironda added. “We know that the sooner we address these pain conditions the less likely they are to become truly chronic—or, if they become chronic, the less likely they are to be severe.”

Dr. Gironda said that it is unknown how many of these soldiers had chronic pain complaints before they entered a war zone. It also is difficult to say how the prevalence and severity of these complaints compare with those in the general public.

For example, a recent survey by researcher Michael Von Korff, Sc.D., and colleagues at Group Health Cooperative in Seattle estimated that nearly 20% of all adult Americans had chronic spinal pain in the prior 12 months (Pain 2005;113:331–9). The majority of those with chronic spinal pain (87%) reported at least one other chronic pain condition, physical ailment, mental disorder, or substance abuse problem.

By that standard, the prevalence of chronic pain conditions in hospitalized veterans may not be all that much greater than it is among their noncombatant peers. How the severity and duration of their complaints compare with the general population is unclear.

BOSTON — Chronic pain was the most frequent complaint among U.S. soldiers returning from foreign war zones, according to findings from a new survey of patients at a Florida veterans' hospital.

The high prevalence and severity of chronic pain syndromes among veterans may result from stress and hardship rather than wounds, according to a report presented in a poster at the annual meeting of the American Pain Society.

Ronald Gironda, Ph.D., and his associates at the James A. Haley Veterans Affairs Medical Center in Tampa, Fla., reviewed records of 793 patients who were veterans of conflicts in Afghanistan and Iraq through November 2004.

None of the patients suffered gunshot wounds or blast injuries, he said.

About 47% of patients (373) reported pain. Some 28% (222 patients) reported pain scores of 4 or greater on a scale of 0–10. The researchers randomly selected 100 patient records from this group for closer inspection.

In the subgroup with significant pain, the average pain score was 6.6—considered “significant pain that is likely to interfere with functional activity,” said Dr. Gironda, a pain specialist.

The veterans' primary complaints were back pain (46%), lower limb pain (31%), upper limb pain (7.5%), neck pain (6%), and headache (4.5%).

“I think when all is said and done we're going to see even higher rates of pain in this new group of veterans than we saw in the Persian Gulf War,” Dr. Gironda told FAMILY PRACTICE NEWS.

The pain patients suffered a gauntlet of assaults on their well-being. Many had become physically inactive and deconditioned since their return. “They were often depressed, demoralized, unemployed, and had no social contact,” he noted.

“We know that there is a relationship between psychosocial factors and the report of pain—how it is experienced and how it develops and unfolds over time,” Dr. Gironda said. “One of the main goals of treatment is to help these individuals develop skills to cope with the pain.”

In addition to providing medical therapy, a 3-week interdisciplinary pain program introduces veterans to new exercise regimens, relaxation techniques, and cognitive-behavioral therapy to reduce fear of pain and fear of activity. Within the first week or so they also are weaned off of opiates.

“The VA has a real opportunity here,” Dr. Gironda added. “We know that the sooner we address these pain conditions the less likely they are to become truly chronic—or, if they become chronic, the less likely they are to be severe.”

Dr. Gironda said that it is unknown how many of these soldiers had chronic pain complaints before they entered a war zone. It also is difficult to say how the prevalence and severity of these complaints compare with those in the general public.

For example, a recent survey by researcher Michael Von Korff, Sc.D., and colleagues at Group Health Cooperative in Seattle estimated that nearly 20% of all adult Americans had chronic spinal pain in the prior 12 months (Pain 2005;113:331–9). The majority of those with chronic spinal pain (87%) reported at least one other chronic pain condition, physical ailment, mental disorder, or substance abuse problem.

By that standard, the prevalence of chronic pain conditions in hospitalized veterans may not be all that much greater than it is among their noncombatant peers. How the severity and duration of their complaints compare with the general population is unclear.

BOSTON — Chronic pain was the most frequent complaint among U.S. soldiers returning from foreign war zones, according to findings from a new survey of patients at a Florida veterans' hospital.

The high prevalence and severity of chronic pain syndromes among veterans may result from stress and hardship rather than wounds, according to a report presented in a poster at the annual meeting of the American Pain Society.

Ronald Gironda, Ph.D., and his associates at the James A. Haley Veterans Affairs Medical Center in Tampa, Fla., reviewed records of 793 patients who were veterans of conflicts in Afghanistan and Iraq through November 2004.

None of the patients suffered gunshot wounds or blast injuries, he said.

About 47% of patients (373) reported pain. Some 28% (222 patients) reported pain scores of 4 or greater on a scale of 0–10. The researchers randomly selected 100 patient records from this group for closer inspection.

In the subgroup with significant pain, the average pain score was 6.6—considered “significant pain that is likely to interfere with functional activity,” said Dr. Gironda, a pain specialist.

The veterans' primary complaints were back pain (46%), lower limb pain (31%), upper limb pain (7.5%), neck pain (6%), and headache (4.5%).

“I think when all is said and done we're going to see even higher rates of pain in this new group of veterans than we saw in the Persian Gulf War,” Dr. Gironda told FAMILY PRACTICE NEWS.

The pain patients suffered a gauntlet of assaults on their well-being. Many had become physically inactive and deconditioned since their return. “They were often depressed, demoralized, unemployed, and had no social contact,” he noted.

“We know that there is a relationship between psychosocial factors and the report of pain—how it is experienced and how it develops and unfolds over time,” Dr. Gironda said. “One of the main goals of treatment is to help these individuals develop skills to cope with the pain.”

In addition to providing medical therapy, a 3-week interdisciplinary pain program introduces veterans to new exercise regimens, relaxation techniques, and cognitive-behavioral therapy to reduce fear of pain and fear of activity. Within the first week or so they also are weaned off of opiates.

“The VA has a real opportunity here,” Dr. Gironda added. “We know that the sooner we address these pain conditions the less likely they are to become truly chronic—or, if they become chronic, the less likely they are to be severe.”

Dr. Gironda said that it is unknown how many of these soldiers had chronic pain complaints before they entered a war zone. It also is difficult to say how the prevalence and severity of these complaints compare with those in the general public.

For example, a recent survey by researcher Michael Von Korff, Sc.D., and colleagues at Group Health Cooperative in Seattle estimated that nearly 20% of all adult Americans had chronic spinal pain in the prior 12 months (Pain 2005;113:331–9). The majority of those with chronic spinal pain (87%) reported at least one other chronic pain condition, physical ailment, mental disorder, or substance abuse problem.

By that standard, the prevalence of chronic pain conditions in hospitalized veterans may not be all that much greater than it is among their noncombatant peers. How the severity and duration of their complaints compare with the general population is unclear.