University of Colorado: Annual Internal Medicine Program

ESTES PARK, COLO. – S-adenosyl-L-methionine (SAMe) doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, SAMe is "buzz worthy," Dr. Lisa Corbin declared at an update on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she cited as the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the University of Colorado Hospital’s Center for Integrative Medicine in Aurora and a general internist at the university.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective": the National Institutes of Health–backed DASH diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Depression

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine, as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies showed that SAMe was superior to placebo, with an efficacy equivalent to that of tricyclic antidepressants, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg b.i.d., increased after 2 weeks to 800 mg b.i.d.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below 7 occurred in 26% of the SAMe group compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number-needed-to-treat as 6 to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was 7 (Am. J. Psychiatry 2010;167:942-8). "Those are actually pretty good NNTs," the internist observed.

Osteoarthritis

SAMe appears to increase proteoglycans synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to non-cyclo-oxygenase 2--selective NSAIDs, but with fewer side effects.

In a University of California, Irvine, 16-week, double-blind, crossover trial involving 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped (BMC Musculoskelet. Disord. 2004 [doi:10.1186/1471-2474-5-6]) .

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different than with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends for better outcomes than with placebo (Scand. J. Rheumatol. 1997;26:206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She said she urges her patients who are interested in trying dietary supplements to seek out those with ‘USP Verified’ displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosyl-L-methionine (SAMe) doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, SAMe is "buzz worthy," Dr. Lisa Corbin declared at an update on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she cited as the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the University of Colorado Hospital’s Center for Integrative Medicine in Aurora and a general internist at the university.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective": the National Institutes of Health–backed DASH diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Depression

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine, as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies showed that SAMe was superior to placebo, with an efficacy equivalent to that of tricyclic antidepressants, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg b.i.d., increased after 2 weeks to 800 mg b.i.d.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below 7 occurred in 26% of the SAMe group compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number-needed-to-treat as 6 to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was 7 (Am. J. Psychiatry 2010;167:942-8). "Those are actually pretty good NNTs," the internist observed.

Osteoarthritis

SAMe appears to increase proteoglycans synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to non-cyclo-oxygenase 2--selective NSAIDs, but with fewer side effects.

In a University of California, Irvine, 16-week, double-blind, crossover trial involving 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped (BMC Musculoskelet. Disord. 2004 [doi:10.1186/1471-2474-5-6]) .

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different than with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends for better outcomes than with placebo (Scand. J. Rheumatol. 1997;26:206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She said she urges her patients who are interested in trying dietary supplements to seek out those with ‘USP Verified’ displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosyl-L-methionine (SAMe) doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, SAMe is "buzz worthy," Dr. Lisa Corbin declared at an update on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she cited as the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the University of Colorado Hospital’s Center for Integrative Medicine in Aurora and a general internist at the university.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective": the National Institutes of Health–backed DASH diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Depression

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine, as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies showed that SAMe was superior to placebo, with an efficacy equivalent to that of tricyclic antidepressants, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg b.i.d., increased after 2 weeks to 800 mg b.i.d.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below 7 occurred in 26% of the SAMe group compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number-needed-to-treat as 6 to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was 7 (Am. J. Psychiatry 2010;167:942-8). "Those are actually pretty good NNTs," the internist observed.

Osteoarthritis

SAMe appears to increase proteoglycans synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to non-cyclo-oxygenase 2--selective NSAIDs, but with fewer side effects.

In a University of California, Irvine, 16-week, double-blind, crossover trial involving 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped (BMC Musculoskelet. Disord. 2004 [doi:10.1186/1471-2474-5-6]) .

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different than with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends for better outcomes than with placebo (Scand. J. Rheumatol. 1997;26:206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She said she urges her patients who are interested in trying dietary supplements to seek out those with ‘USP Verified’ displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – Patients hospitalized for prolonged biliary colic cholecystitis should be medically stabilized and then undergo cholecystectomy during the same admission, Dr. David Tanaka advised at a conference on internal medicine sponsored by the University of Colorado.

"I think that’s one of the big changes in the way we do things now. There’s really no benefit to cooling them off and sending them home and having them see the surgeon later. In fact, their outcomes are worse if you do that," according to Dr. Tanaka, a general internist at the university.

A major influence on this change in thinking was a meta-analysis involving five randomized clinical trials of early versus delayed laparoscopic cholecystectomy, with the delayed procedures being performed 6-12 weeks after symptoms settled. The analysis included 451 randomized patients with cholecystitis.

The incidence of bile duct injury was 36% lower and the conversion rate to open cholecystectomy was 12% lower in the early-surgery group, although neither of these differences achieved statistical significance.

However, the early-surgery group also averaged a mean 4.12-day shorter total hospital stay than did patients undergoing late cholecystectomy, and that difference was highly significant. Also, 17.5% of patients randomized to delayed laparoscopic surgery wound up undergoing emergency surgery as a consequence of incomplete resolution or recurrence of their cholecystitis during the waiting period. Fully 45% of these emergency laparoscopic cholecystectomies required conversion to open procedures (Br. J. Surg. 2010;97:141-50).

Ten to 15% of adults in Western countries have gallstones, and each year 1%-4% of these individuals become symptomatic. In the United States, historically only about 30% of patients with acute cholecystitis have undergone cholecystectomy during the acute episode.

It’s particularly important that patients admitted with gallstone pancreatitis undergo cholecystectomy prior to discharge. Otherwise they are at risk for frequent recurrences, Dr. Tanaka noted. Surgeons won’t want to operate on them when they have pancreatitis, though, so it’s necessary to treat that condition first. Preoperative endoscopic retrograde cholangiopancreatography is not indicated in all patients with gallstone pancreatitis, but it has been shown to be beneficial in those with persistent obstructive jaundice and/or biliary sepsis, he continued.

Most patients with gallbladder and common bile duct stones undergo preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy. However, a recent meta-analysis demonstrated that intraoperative endoscopic sphincterotomy carried out during laparoscopic cholecystectomy is just as safe and effective as preoperative endoscopic sphincterotomy. And in this meta-analysis involving four randomized trials with 532 patients, intraoperative endoscopic sphincterotomy was associated with a mean 3-day shorter hospital stay (Br. J. Surg. 2011;98:908-16).

"So if you can get your gastroenterologist to coordinate with the surgeons to do it at the time of surgery, you’re probably going to save some hospital days," Dr. Tanaka said.

He reported having no financial conflicts.

ESTES PARK, COLO. – Patients hospitalized for prolonged biliary colic cholecystitis should be medically stabilized and then undergo cholecystectomy during the same admission, Dr. David Tanaka advised at a conference on internal medicine sponsored by the University of Colorado.

"I think that’s one of the big changes in the way we do things now. There’s really no benefit to cooling them off and sending them home and having them see the surgeon later. In fact, their outcomes are worse if you do that," according to Dr. Tanaka, a general internist at the university.

A major influence on this change in thinking was a meta-analysis involving five randomized clinical trials of early versus delayed laparoscopic cholecystectomy, with the delayed procedures being performed 6-12 weeks after symptoms settled. The analysis included 451 randomized patients with cholecystitis.

The incidence of bile duct injury was 36% lower and the conversion rate to open cholecystectomy was 12% lower in the early-surgery group, although neither of these differences achieved statistical significance.

However, the early-surgery group also averaged a mean 4.12-day shorter total hospital stay than did patients undergoing late cholecystectomy, and that difference was highly significant. Also, 17.5% of patients randomized to delayed laparoscopic surgery wound up undergoing emergency surgery as a consequence of incomplete resolution or recurrence of their cholecystitis during the waiting period. Fully 45% of these emergency laparoscopic cholecystectomies required conversion to open procedures (Br. J. Surg. 2010;97:141-50).

Ten to 15% of adults in Western countries have gallstones, and each year 1%-4% of these individuals become symptomatic. In the United States, historically only about 30% of patients with acute cholecystitis have undergone cholecystectomy during the acute episode.

It’s particularly important that patients admitted with gallstone pancreatitis undergo cholecystectomy prior to discharge. Otherwise they are at risk for frequent recurrences, Dr. Tanaka noted. Surgeons won’t want to operate on them when they have pancreatitis, though, so it’s necessary to treat that condition first. Preoperative endoscopic retrograde cholangiopancreatography is not indicated in all patients with gallstone pancreatitis, but it has been shown to be beneficial in those with persistent obstructive jaundice and/or biliary sepsis, he continued.

Most patients with gallbladder and common bile duct stones undergo preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy. However, a recent meta-analysis demonstrated that intraoperative endoscopic sphincterotomy carried out during laparoscopic cholecystectomy is just as safe and effective as preoperative endoscopic sphincterotomy. And in this meta-analysis involving four randomized trials with 532 patients, intraoperative endoscopic sphincterotomy was associated with a mean 3-day shorter hospital stay (Br. J. Surg. 2011;98:908-16).

"So if you can get your gastroenterologist to coordinate with the surgeons to do it at the time of surgery, you’re probably going to save some hospital days," Dr. Tanaka said.

He reported having no financial conflicts.

ESTES PARK, COLO. – Patients hospitalized for prolonged biliary colic cholecystitis should be medically stabilized and then undergo cholecystectomy during the same admission, Dr. David Tanaka advised at a conference on internal medicine sponsored by the University of Colorado.

"I think that’s one of the big changes in the way we do things now. There’s really no benefit to cooling them off and sending them home and having them see the surgeon later. In fact, their outcomes are worse if you do that," according to Dr. Tanaka, a general internist at the university.

A major influence on this change in thinking was a meta-analysis involving five randomized clinical trials of early versus delayed laparoscopic cholecystectomy, with the delayed procedures being performed 6-12 weeks after symptoms settled. The analysis included 451 randomized patients with cholecystitis.

The incidence of bile duct injury was 36% lower and the conversion rate to open cholecystectomy was 12% lower in the early-surgery group, although neither of these differences achieved statistical significance.

However, the early-surgery group also averaged a mean 4.12-day shorter total hospital stay than did patients undergoing late cholecystectomy, and that difference was highly significant. Also, 17.5% of patients randomized to delayed laparoscopic surgery wound up undergoing emergency surgery as a consequence of incomplete resolution or recurrence of their cholecystitis during the waiting period. Fully 45% of these emergency laparoscopic cholecystectomies required conversion to open procedures (Br. J. Surg. 2010;97:141-50).

Ten to 15% of adults in Western countries have gallstones, and each year 1%-4% of these individuals become symptomatic. In the United States, historically only about 30% of patients with acute cholecystitis have undergone cholecystectomy during the acute episode.

It’s particularly important that patients admitted with gallstone pancreatitis undergo cholecystectomy prior to discharge. Otherwise they are at risk for frequent recurrences, Dr. Tanaka noted. Surgeons won’t want to operate on them when they have pancreatitis, though, so it’s necessary to treat that condition first. Preoperative endoscopic retrograde cholangiopancreatography is not indicated in all patients with gallstone pancreatitis, but it has been shown to be beneficial in those with persistent obstructive jaundice and/or biliary sepsis, he continued.

Most patients with gallbladder and common bile duct stones undergo preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy. However, a recent meta-analysis demonstrated that intraoperative endoscopic sphincterotomy carried out during laparoscopic cholecystectomy is just as safe and effective as preoperative endoscopic sphincterotomy. And in this meta-analysis involving four randomized trials with 532 patients, intraoperative endoscopic sphincterotomy was associated with a mean 3-day shorter hospital stay (Br. J. Surg. 2011;98:908-16).

"So if you can get your gastroenterologist to coordinate with the surgeons to do it at the time of surgery, you’re probably going to save some hospital days," Dr. Tanaka said.

He reported having no financial conflicts.

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

ESTES PARK, COLO. – The high false-positive rates for autoimmune serologies make them unsuitable as screening tests for connective tissue diseases, according to Dr. Robert W. Janson.

Moreover, the prearranged test panels often pitched to primary care physicians are a particularly bad idea, he said. These panels might combine, for example, rheumatoid factor (RF), antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein.

"I call them ‘rheum rally packs.’ They should be avoided. They can multiply testing errors, leading to additional unnecessary testing, needless angst, and inappropriate treatment," said Dr. Janson, chief of the rheumatology section at the Denver Veterans Affairs Medical Center.

Selectivity is the watchword when ordering autoimmune serologic tests. Their value comes when suspicion of a connective tissue disease (CTD) is already high based on history and physical examination, that is, when the pretest probability is relatively high, he explained at an update on internal medicine sponsored by the University of Colorado.

Take, for example, rheumatoid factor. The very name is a misnomer, suggesting a high test specificity that’s completely undeserved. While 80% of patients with rheumatoid arthritis are indeed RF+, the test is also positive in the majority of individuals with Sjögren’s syndrome or mixed CDT; in many patients with chronic infection, malignancy, or fibrotic pulmonary disorders; and even in 5% of healthy individuals. As a result, the test’s positive predictive value for rheumatoid arthritis is a mere 24%, although its negative predictive value is much better at 89%.

"Rheumatoid factor has little value as a screening test to diagnose or exclude CTD in patients with just plain arthralgias. It has a much higher positive predictive value if ordered selectively in patients with a higher probability of a CTD: morning stiffness, sicca symptoms, and arthralgias or synovitis in a rheumatoid arthritis distribution," the rheumatologist continued.

The combination of a positive RF and a positive test for anticyclic citrullinated peptide antibodies (ACPAs) is associated with a nearly 100% likelihood that an appropriately symptomatic patient has rheumatoid arthritis. Also, when both tests are positive, it’s an indicator of a more serious case of rheumatoid arthritis that will involve joint damage and disability.

"These patients need more aggressive therapy," Dr. Janson noted.

On the other hand, he said he’d urge that a patient with morning stiffness lasting longer than 1 hour, tenderness of the metacarpophalangeal or metatarsophalangeal joints, and suspected synovitis on physical examination be referred to a rheumatologist to see if an early inflammatory arthritis is involved, even if the RF and/or ACPA tests are negative. In this era of highly effective biologic therapy, negative serologic tests don’t preclude early and aggressive therapy, he noted.

Nearly all patients with SLE will have a positive antinuclear antibody (ANA) test. A negative test rules out SLE with 95% certainty. But the test’s positive predictive value for SLE is only 11%-30% because so many other conditions are associated with a positive ANA. These include numerous other CTDs, organ-specific autoimmune diseases such as Hashimoto’s thyroiditis, a variety of chronic infections, and lymphoproliferative disorders. In addition, low-titer positive ANA tests are not uncommon in normal women and the elderly.

In sum, ANA testing is useful to help establish a diagnosis when a patient’s clinical features suggest a CTD, as well as for excluding CTDs in patients with uncertain clinical findings, and in monitoring CTD disease activity. Rheumatologists consider ANA titers of 1:320 or higher to be more clinically meaningful, according to Dr. Janson.

He singled out a particular ANA subantibody test – that for antihistone antibodies – as one that "approaches being the perfect test." That’s because patients with drug-induced lupus don’t make antibodies to nonhistone nuclear antigens. As a result, antihistone antibody testing enjoys greater than 95% sensitivity and specificity for drug-induced lupus.

Two ANA subantibody tests are highly diagnostic for SLE. These are anti–double-stranded DNA and anti–Smith antibody tests, each with a specificity in excess of 95% for SLE.

The antineutrophil cytoplasmic antibody (ANCA) tests are the first serologies to order when a patient is suspected of having some kind of vasculitis as manifest, for example, by diffuse alveolar hemorrhage, nephritis without another explanation, or a pulmonary-renal syndrome.

ANCAs come in two types: cytoplasmic (cANCA), which are antibodies directed against proteinase 3, and perinuclear (pANCA), directed most often against myeloperoxidase.

The cANCA test has 98% specificity for active generalized granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis. However, limited granulomatosis with polyangiitis affecting, say, the sinuses but without kidney involvement may be ANCA negative in 40% of cases.

The pANCA test has 60%-90% sensitivity for microscopic polyangiitis, but poor sensitivity, as the test can be positive in rheumatoid arthritis and several other CTDs. However, the specificity for microscopic polyangiitis improves to greater than 95% in the setting of both positive pANCA and antimyeloperoxidase ELISA tests.

The acute phase reactants – C-reactive protein and ESR are useful in assessing patients with a suspected malignancy or infection, as well as in those in whom inflammatory arthritides or vasculitis is a concern. A CRP greater than 1.0 mg/dL indicates significant inflammation, and a value in excess of 10 mg/dL is due either to metastatic cancer, bacterial infection, or systemic vasculitis. And if both the ESR and CRP are normal, the probability that a patient has a vasculitis is "incredibly low," Dr. Janson said.

At least 80% of patients with polymyalgia rheumatica will have an elevated ESR, and the CRP should be elevated in those that don’t.

Dr. Janson reported having no relevant financial conflicts.

ESTES PARK, COLO. – Look in the near future for widespread adoption of a more selective approach to getting chest radiographs after pneumonia.

Since 2000, the American Thoracic Society, the British Thoracic Society, and the Canadian Infectious Diseases Society along with the Canadian Thoracic Society have published guidelines for management of community-acquired pneumonia. The guidelines recommend a routine follow-up chest x-ray within a couple of months after the treatment of pneumonia. The main purpose, other than in the minority of patients with ongoing pneumonia-related symptoms, is to exclude an underlying lung cancer that may have predisposed to the pneumonia.

However, recent studies suggest that the diagnostic yield of these follow-up radiographs is too low to justify a recommendation for routine imaging. The contention is that only the subset of pneumonia patients who are at increased risk for lung cancer should be targeted for a follow-up chest x-ray. A more selective approach will save substantial health care dollars and reduce radiation exposure, according to Dr. Robert L. Keith, professor of medicine and a pulmonologist at the University of Colorado at Denver, Aurora, which sponsored this update in internal medicine.

He cited what he considers "a great study" by Canadian investigators who conducted a population-based study of 3,398 Edmonton patients who had been followed for 5 years after treatment of pneumonia. The incidence of diagnosis of new lung cancer was 1.1% at 90 days, 1.7% at 1 year, and 2.3% at 5 years, which the investigators deemed too low to provide a strong rationale for routine follow-up chest x-rays (Arch. Intern. Med. 2011;171:1193-8).

Only 40% of the patients had had a follow-up chest x-ray within 90 days, suggesting that the majority of Edmonton-area physicians were already skeptical about guideline-recommended routine postpneumonia radiography. The diagnostic yield of lung cancer achieved via the imaging studies was 2.5%.

A key study finding was that none of the 79 lung cancers that were diagnosed within 5 years following pneumonia occurred in patients younger than age 40 years at the time of their lung infection, and only five cases occurred in 40- to 49-year-olds. The investigators identified three independent risk factors associated with lung cancer within 5 years after an episode of pneumonia: age 50 years or more, with a relative risk of 19; male sex, with a 1.8-fold increased risk; and current smoking, with a relative risk of 1.7.

Dr. Keith predicted that most health care systems are going to endorse the lung cancer screening strategy that proved so successful in the landmark National Lung Screening Trial (N. Engl. J. Med. 2011;365:395-409). That study in more than 50,000 subjects showed that screening via low-dose helical chest CT reduced lung cancer mortality by 20%, compared with screening by chest x-ray in high-risk patients as defined mainly by their age and smoking history.

Based upon the results of this National Cancer Institute–sponsored study and other recent lung cancer screening studies, the National Comprehensive Cancer Network has recommended routine screening using low-dose helical CT for two high-risk groups: individuals aged 55-74 years with at least 30 pack-years of smoking who either are current smokers or who quit fewer than 15 years ago, and patients aged 50 or older with at least 20 pack-years of smoking and one additional risk factor. The additional risk factors are contact with radon, occupational exposure to asbestos or other carcinogens, a history of lung cancer in a first-degree relative, a personal history of any tobacco-related aerodigestive cancer, or chronic obstructive pulmonary disease.

Dr. Keith reported that he serves on the speakers bureaus for Boehringer Ingelheim and Pfizer.

ESTES PARK, COLO. – Look in the near future for widespread adoption of a more selective approach to getting chest radiographs after pneumonia.

Since 2000, the American Thoracic Society, the British Thoracic Society, and the Canadian Infectious Diseases Society along with the Canadian Thoracic Society have published guidelines for management of community-acquired pneumonia. The guidelines recommend a routine follow-up chest x-ray within a couple of months after the treatment of pneumonia. The main purpose, other than in the minority of patients with ongoing pneumonia-related symptoms, is to exclude an underlying lung cancer that may have predisposed to the pneumonia.

However, recent studies suggest that the diagnostic yield of these follow-up radiographs is too low to justify a recommendation for routine imaging. The contention is that only the subset of pneumonia patients who are at increased risk for lung cancer should be targeted for a follow-up chest x-ray. A more selective approach will save substantial health care dollars and reduce radiation exposure, according to Dr. Robert L. Keith, professor of medicine and a pulmonologist at the University of Colorado at Denver, Aurora, which sponsored this update in internal medicine.

He cited what he considers "a great study" by Canadian investigators who conducted a population-based study of 3,398 Edmonton patients who had been followed for 5 years after treatment of pneumonia. The incidence of diagnosis of new lung cancer was 1.1% at 90 days, 1.7% at 1 year, and 2.3% at 5 years, which the investigators deemed too low to provide a strong rationale for routine follow-up chest x-rays (Arch. Intern. Med. 2011;171:1193-8).

Only 40% of the patients had had a follow-up chest x-ray within 90 days, suggesting that the majority of Edmonton-area physicians were already skeptical about guideline-recommended routine postpneumonia radiography. The diagnostic yield of lung cancer achieved via the imaging studies was 2.5%.

A key study finding was that none of the 79 lung cancers that were diagnosed within 5 years following pneumonia occurred in patients younger than age 40 years at the time of their lung infection, and only five cases occurred in 40- to 49-year-olds. The investigators identified three independent risk factors associated with lung cancer within 5 years after an episode of pneumonia: age 50 years or more, with a relative risk of 19; male sex, with a 1.8-fold increased risk; and current smoking, with a relative risk of 1.7.

Dr. Keith predicted that most health care systems are going to endorse the lung cancer screening strategy that proved so successful in the landmark National Lung Screening Trial (N. Engl. J. Med. 2011;365:395-409). That study in more than 50,000 subjects showed that screening via low-dose helical chest CT reduced lung cancer mortality by 20%, compared with screening by chest x-ray in high-risk patients as defined mainly by their age and smoking history.

Based upon the results of this National Cancer Institute–sponsored study and other recent lung cancer screening studies, the National Comprehensive Cancer Network has recommended routine screening using low-dose helical CT for two high-risk groups: individuals aged 55-74 years with at least 30 pack-years of smoking who either are current smokers or who quit fewer than 15 years ago, and patients aged 50 or older with at least 20 pack-years of smoking and one additional risk factor. The additional risk factors are contact with radon, occupational exposure to asbestos or other carcinogens, a history of lung cancer in a first-degree relative, a personal history of any tobacco-related aerodigestive cancer, or chronic obstructive pulmonary disease.

Dr. Keith reported that he serves on the speakers bureaus for Boehringer Ingelheim and Pfizer.

ESTES PARK, COLO. – Look in the near future for widespread adoption of a more selective approach to getting chest radiographs after pneumonia.

Since 2000, the American Thoracic Society, the British Thoracic Society, and the Canadian Infectious Diseases Society along with the Canadian Thoracic Society have published guidelines for management of community-acquired pneumonia. The guidelines recommend a routine follow-up chest x-ray within a couple of months after the treatment of pneumonia. The main purpose, other than in the minority of patients with ongoing pneumonia-related symptoms, is to exclude an underlying lung cancer that may have predisposed to the pneumonia.

However, recent studies suggest that the diagnostic yield of these follow-up radiographs is too low to justify a recommendation for routine imaging. The contention is that only the subset of pneumonia patients who are at increased risk for lung cancer should be targeted for a follow-up chest x-ray. A more selective approach will save substantial health care dollars and reduce radiation exposure, according to Dr. Robert L. Keith, professor of medicine and a pulmonologist at the University of Colorado at Denver, Aurora, which sponsored this update in internal medicine.

He cited what he considers "a great study" by Canadian investigators who conducted a population-based study of 3,398 Edmonton patients who had been followed for 5 years after treatment of pneumonia. The incidence of diagnosis of new lung cancer was 1.1% at 90 days, 1.7% at 1 year, and 2.3% at 5 years, which the investigators deemed too low to provide a strong rationale for routine follow-up chest x-rays (Arch. Intern. Med. 2011;171:1193-8).

Only 40% of the patients had had a follow-up chest x-ray within 90 days, suggesting that the majority of Edmonton-area physicians were already skeptical about guideline-recommended routine postpneumonia radiography. The diagnostic yield of lung cancer achieved via the imaging studies was 2.5%.

A key study finding was that none of the 79 lung cancers that were diagnosed within 5 years following pneumonia occurred in patients younger than age 40 years at the time of their lung infection, and only five cases occurred in 40- to 49-year-olds. The investigators identified three independent risk factors associated with lung cancer within 5 years after an episode of pneumonia: age 50 years or more, with a relative risk of 19; male sex, with a 1.8-fold increased risk; and current smoking, with a relative risk of 1.7.

Dr. Keith predicted that most health care systems are going to endorse the lung cancer screening strategy that proved so successful in the landmark National Lung Screening Trial (N. Engl. J. Med. 2011;365:395-409). That study in more than 50,000 subjects showed that screening via low-dose helical chest CT reduced lung cancer mortality by 20%, compared with screening by chest x-ray in high-risk patients as defined mainly by their age and smoking history.

Based upon the results of this National Cancer Institute–sponsored study and other recent lung cancer screening studies, the National Comprehensive Cancer Network has recommended routine screening using low-dose helical CT for two high-risk groups: individuals aged 55-74 years with at least 30 pack-years of smoking who either are current smokers or who quit fewer than 15 years ago, and patients aged 50 or older with at least 20 pack-years of smoking and one additional risk factor. The additional risk factors are contact with radon, occupational exposure to asbestos or other carcinogens, a history of lung cancer in a first-degree relative, a personal history of any tobacco-related aerodigestive cancer, or chronic obstructive pulmonary disease.

Dr. Keith reported that he serves on the speakers bureaus for Boehringer Ingelheim and Pfizer.

ESTES PARK, COLO. – S-adenosyl-l-methionine doesn’t crack the annual top-10 lists of the most widely used nutritional supplements in complementary and alternative medicine surveys. But unlike other far more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, S-adenosyl-l-methionine (SAMe) is "buzz-worthy," Dr. Lisa Corbin declared at a conference on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado in Denver.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective," namely the National Institutes of Health–backed DASH (Dietary Approaches to Stop Hypertension) diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Osteoarthritis

SAMe appears to increase proteoglycan synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to that of non-cyclooxygenase-2 (non-COX2) inhibitor selective nonsteroidal anti-inflammatory drugs (NSAIDs), but with fewer side effects.

And in a University of California, Irvine, 16-week, double-blind, crossover trial of 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d. and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped.

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different from those with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends toward better outcomes compared with placebo (Scand. J. Rheumatol. 1997; 26: 206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosyl-l-methionine doesn’t crack the annual top-10 lists of the most widely used nutritional supplements in complementary and alternative medicine surveys. But unlike other far more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, S-adenosyl-l-methionine (SAMe) is "buzz-worthy," Dr. Lisa Corbin declared at a conference on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado in Denver.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective," namely the National Institutes of Health–backed DASH (Dietary Approaches to Stop Hypertension) diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Osteoarthritis

SAMe appears to increase proteoglycan synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to that of non-cyclooxygenase-2 (non-COX2) inhibitor selective nonsteroidal anti-inflammatory drugs (NSAIDs), but with fewer side effects.

And in a University of California, Irvine, 16-week, double-blind, crossover trial of 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d. and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped.

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different from those with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends toward better outcomes compared with placebo (Scand. J. Rheumatol. 1997; 26: 206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosyl-l-methionine doesn’t crack the annual top-10 lists of the most widely used nutritional supplements in complementary and alternative medicine surveys. But unlike other far more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, S-adenosyl-l-methionine (SAMe) is "buzz-worthy," Dr. Lisa Corbin declared at a conference on internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado in Denver.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective," namely the National Institutes of Health–backed DASH (Dietary Approaches to Stop Hypertension) diet.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

Osteoarthritis

SAMe appears to increase proteoglycan synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to that of non-cyclooxygenase-2 (non-COX2) inhibitor selective nonsteroidal anti-inflammatory drugs (NSAIDs), but with fewer side effects.

And in a University of California, Irvine, 16-week, double-blind, crossover trial of 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d. and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.

SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped.

Fibromyalgia

Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different from those with placebo (Scand. J. Rheumatol. 1991;20:294-302).

Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends toward better outcomes compared with placebo (Scand. J. Rheumatol. 1997; 26: 206-11).

Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – Primary care physicians appear to have dropped the ball when it comes to primary chemoprevention of breast cancer, studies suggest.

Chemoprevention is enormously underutilized. An estimated 2 million American premenopausal women are candidates for primary chemoprevention of breast cancer with tamoxifen, an agent shown to reduce their risk by 50%. Yet only 4% of them are on this safe and generally well-tolerated estrogen receptor antagonist, Dr. Jennifer R. Diamond said at an update in internal medicine sponsored by the University of Colorado at Denver.

Moreover, when she informally polled her audience at the outset of her talk, 93% indicated via electronic clicker that they were not comfortable with chemoprevention for breast cancer and didn’t commonly use it in appropriately selected patients in their practice.

"The most common side effect I see with tamoxifen for primary chemoprevention is hot flashes. But many young women will do fine. They don’t have any problems. And the opportunity to reduce the risk of breast cancer by 50% in these young women makes this an option I think you really need to be offering to young women" who are at increased risk for breast cancer, said Dr. Diamond, a medical oncologist at the university.

Nearly 230,000 American women will receive a new diagnosis of breast cancer in 2012. More than 39,000 women will die this year from the malignancy.

Secondary chemoprevention is most effective for women who have been diagnosed with lobular carcinoma in situ. The recommendation to embark on secondary chemoprevention usually comes from the patient’s medical oncologist.

In contrast, most candidates for primary chemoprevention have never seen a medical oncologist. Thus, primary chemoprevention falls within the bailiwick of primary care physicians. The latest guidelines from the National Comprehensive Cancer Network identify appropriate candidates for primary chemoprevention as women who have a first-degree relative with breast or ovarian cancer; a history of thoracic irradiation; mutations predisposing to breast cancer; or a 5-year risk of breast cancer of at least 1.7% according to the breast cancer risk assessment tool (the Gail model).

A 5-year risk of 1.7% or greater is not a high bar. It equates on the Gail model to being 65 years old without additional risk factors. "You’ll find that many of your patients are candidates," Dr. Diamond predicted.

Two options are available for primary chemoprevention; the determining factor as to which is best in a given high-risk individual is menopausal status. Premenopausal women can benefit from 5 years of oral tamoxifen at 20 mg/day. In postmenopausal women, however, exemestane (Aromasin), an aromatase inhibitor, is the safer, better choice, even though the drug’s use in chemoprevention is, for now, off label, she continued.

The oft-cited figure of a 50% reduction in breast cancer risk conferred by tamoxifen comes from the landmark randomized, placebo-controlled NSABP (National Surgical Adjuvant Breast and Bowel Project) P-1 trial (J. Natl. Cancer Inst. 1998;90:1371-88). The protective effect continued after treatment ended. The number needed to treat at 20 mg/day for 5 years in order to prevent one additional case of breast cancer was calculated at 95 in 5 years and 56 in 10 years. Women younger than age 50 years experienced no excess risk of serious adverse events.

"The risks of venous thromboembolism and endometrial cancer are what we all worry about with tamoxifen, but they’re actually incredibly uncommon" in women younger than age 50, she said. "I don’t recommend that you use tamoxifen in your postmenopausal women; that’s where you get into trouble with endometrial cancer and thromboembolic events. I believe that you can safely use tamoxifen in premenopausal women without a significantly increased risk of thromboembolic events. I equate the risk to that of birth control pills."

Raloxifene joins tamoxifen as the only other proved drug with Food and Drug Administration approval for primary breast cancer chemoprevention. The NSABP STAR (Study of Tamoxifen and Raloxifene) trial showed that the two medications are equivalent for prevention of invasive breast cancer, but that raloxifene is less effective in preventing ductal carcinoma in situ (JAMA 2006;295:2727-41). For this reason, Dr. Diamond and her colleagues don’t use it.

For postmenopausal women who are candidates for primary chemoprevention, Dr. Diamond said that she turns to exemestane on the basis of the National Cancer Institute of Canada CTG MAP-3 trial, which showed a 65% reduction in the annual incidence of breast cancer with 5 years of the aromatase inhibitor, compared with placebo. (N. Engl. J. Med. 2011;364:2381-91).

The number needed to treat with exemestane at 25 mg/day for 5 years in order to prevent one invasive breast cancer was 94 in 3 years and 26 in 5 years.

"I would argue that this is a really low NNT, and a lot of patients in your practice probably would fall into the category of qualifying for the MAP-3 study," Dr. Diamond said.

There were no serious risks associated with exemestane in MAP-3. Hot flashes and other menopausal symptoms were more common than with placebo, yet reassuringly there was no difference between the exemestane and control groups on quality of life measures.

Bone mineral density decreased over time in the exemestane group; however, patients on the aromatase inhibitor had no increased risk of fractures. Dr. Diamond advised monitoring bone density in exemestane-treated women, and if it drops significantly, consider prescribing denosumab as a subcutaneous injection once every 6 months. Denosumab is already FDA approved to increase bone mass in patients on adjuvant aromatase inhibitor therapy for breast cancer.

Dr. Diamond reported having no financial conflicts.

ESTES PARK, COLO. – Primary care physicians appear to have dropped the ball when it comes to primary chemoprevention of breast cancer, studies suggest.

Chemoprevention is enormously underutilized. An estimated 2 million American premenopausal women are candidates for primary chemoprevention of breast cancer with tamoxifen, an agent shown to reduce their risk by 50%. Yet only 4% of them are on this safe and generally well-tolerated estrogen receptor antagonist, Dr. Jennifer R. Diamond said at an update in internal medicine sponsored by the University of Colorado at Denver.

Moreover, when she informally polled her audience at the outset of her talk, 93% indicated via electronic clicker that they were not comfortable with chemoprevention for breast cancer and didn’t commonly use it in appropriately selected patients in their practice.

"The most common side effect I see with tamoxifen for primary chemoprevention is hot flashes. But many young women will do fine. They don’t have any problems. And the opportunity to reduce the risk of breast cancer by 50% in these young women makes this an option I think you really need to be offering to young women" who are at increased risk for breast cancer, said Dr. Diamond, a medical oncologist at the university.

Nearly 230,000 American women will receive a new diagnosis of breast cancer in 2012. More than 39,000 women will die this year from the malignancy.

Secondary chemoprevention is most effective for women who have been diagnosed with lobular carcinoma in situ. The recommendation to embark on secondary chemoprevention usually comes from the patient’s medical oncologist.

In contrast, most candidates for primary chemoprevention have never seen a medical oncologist. Thus, primary chemoprevention falls within the bailiwick of primary care physicians. The latest guidelines from the National Comprehensive Cancer Network identify appropriate candidates for primary chemoprevention as women who have a first-degree relative with breast or ovarian cancer; a history of thoracic irradiation; mutations predisposing to breast cancer; or a 5-year risk of breast cancer of at least 1.7% according to the breast cancer risk assessment tool (the Gail model).

A 5-year risk of 1.7% or greater is not a high bar. It equates on the Gail model to being 65 years old without additional risk factors. "You’ll find that many of your patients are candidates," Dr. Diamond predicted.

Two options are available for primary chemoprevention; the determining factor as to which is best in a given high-risk individual is menopausal status. Premenopausal women can benefit from 5 years of oral tamoxifen at 20 mg/day. In postmenopausal women, however, exemestane (Aromasin), an aromatase inhibitor, is the safer, better choice, even though the drug’s use in chemoprevention is, for now, off label, she continued.

The oft-cited figure of a 50% reduction in breast cancer risk conferred by tamoxifen comes from the landmark randomized, placebo-controlled NSABP (National Surgical Adjuvant Breast and Bowel Project) P-1 trial (J. Natl. Cancer Inst. 1998;90:1371-88). The protective effect continued after treatment ended. The number needed to treat at 20 mg/day for 5 years in order to prevent one additional case of breast cancer was calculated at 95 in 5 years and 56 in 10 years. Women younger than age 50 years experienced no excess risk of serious adverse events.

"The risks of venous thromboembolism and endometrial cancer are what we all worry about with tamoxifen, but they’re actually incredibly uncommon" in women younger than age 50, she said. "I don’t recommend that you use tamoxifen in your postmenopausal women; that’s where you get into trouble with endometrial cancer and thromboembolic events. I believe that you can safely use tamoxifen in premenopausal women without a significantly increased risk of thromboembolic events. I equate the risk to that of birth control pills."

Raloxifene joins tamoxifen as the only other proved drug with Food and Drug Administration approval for primary breast cancer chemoprevention. The NSABP STAR (Study of Tamoxifen and Raloxifene) trial showed that the two medications are equivalent for prevention of invasive breast cancer, but that raloxifene is less effective in preventing ductal carcinoma in situ (JAMA 2006;295:2727-41). For this reason, Dr. Diamond and her colleagues don’t use it.

For postmenopausal women who are candidates for primary chemoprevention, Dr. Diamond said that she turns to exemestane on the basis of the National Cancer Institute of Canada CTG MAP-3 trial, which showed a 65% reduction in the annual incidence of breast cancer with 5 years of the aromatase inhibitor, compared with placebo. (N. Engl. J. Med. 2011;364:2381-91).

The number needed to treat with exemestane at 25 mg/day for 5 years in order to prevent one invasive breast cancer was 94 in 3 years and 26 in 5 years.

"I would argue that this is a really low NNT, and a lot of patients in your practice probably would fall into the category of qualifying for the MAP-3 study," Dr. Diamond said.

There were no serious risks associated with exemestane in MAP-3. Hot flashes and other menopausal symptoms were more common than with placebo, yet reassuringly there was no difference between the exemestane and control groups on quality of life measures.

Bone mineral density decreased over time in the exemestane group; however, patients on the aromatase inhibitor had no increased risk of fractures. Dr. Diamond advised monitoring bone density in exemestane-treated women, and if it drops significantly, consider prescribing denosumab as a subcutaneous injection once every 6 months. Denosumab is already FDA approved to increase bone mass in patients on adjuvant aromatase inhibitor therapy for breast cancer.

Dr. Diamond reported having no financial conflicts.

ESTES PARK, COLO. – Primary care physicians appear to have dropped the ball when it comes to primary chemoprevention of breast cancer, studies suggest.

Chemoprevention is enormously underutilized. An estimated 2 million American premenopausal women are candidates for primary chemoprevention of breast cancer with tamoxifen, an agent shown to reduce their risk by 50%. Yet only 4% of them are on this safe and generally well-tolerated estrogen receptor antagonist, Dr. Jennifer R. Diamond said at an update in internal medicine sponsored by the University of Colorado at Denver.

Moreover, when she informally polled her audience at the outset of her talk, 93% indicated via electronic clicker that they were not comfortable with chemoprevention for breast cancer and didn’t commonly use it in appropriately selected patients in their practice.

"The most common side effect I see with tamoxifen for primary chemoprevention is hot flashes. But many young women will do fine. They don’t have any problems. And the opportunity to reduce the risk of breast cancer by 50% in these young women makes this an option I think you really need to be offering to young women" who are at increased risk for breast cancer, said Dr. Diamond, a medical oncologist at the university.

Nearly 230,000 American women will receive a new diagnosis of breast cancer in 2012. More than 39,000 women will die this year from the malignancy.

Secondary chemoprevention is most effective for women who have been diagnosed with lobular carcinoma in situ. The recommendation to embark on secondary chemoprevention usually comes from the patient’s medical oncologist.

In contrast, most candidates for primary chemoprevention have never seen a medical oncologist. Thus, primary chemoprevention falls within the bailiwick of primary care physicians. The latest guidelines from the National Comprehensive Cancer Network identify appropriate candidates for primary chemoprevention as women who have a first-degree relative with breast or ovarian cancer; a history of thoracic irradiation; mutations predisposing to breast cancer; or a 5-year risk of breast cancer of at least 1.7% according to the breast cancer risk assessment tool (the Gail model).

A 5-year risk of 1.7% or greater is not a high bar. It equates on the Gail model to being 65 years old without additional risk factors. "You’ll find that many of your patients are candidates," Dr. Diamond predicted.

Two options are available for primary chemoprevention; the determining factor as to which is best in a given high-risk individual is menopausal status. Premenopausal women can benefit from 5 years of oral tamoxifen at 20 mg/day. In postmenopausal women, however, exemestane (Aromasin), an aromatase inhibitor, is the safer, better choice, even though the drug’s use in chemoprevention is, for now, off label, she continued.

The oft-cited figure of a 50% reduction in breast cancer risk conferred by tamoxifen comes from the landmark randomized, placebo-controlled NSABP (National Surgical Adjuvant Breast and Bowel Project) P-1 trial (J. Natl. Cancer Inst. 1998;90:1371-88). The protective effect continued after treatment ended. The number needed to treat at 20 mg/day for 5 years in order to prevent one additional case of breast cancer was calculated at 95 in 5 years and 56 in 10 years. Women younger than age 50 years experienced no excess risk of serious adverse events.

"The risks of venous thromboembolism and endometrial cancer are what we all worry about with tamoxifen, but they’re actually incredibly uncommon" in women younger than age 50, she said. "I don’t recommend that you use tamoxifen in your postmenopausal women; that’s where you get into trouble with endometrial cancer and thromboembolic events. I believe that you can safely use tamoxifen in premenopausal women without a significantly increased risk of thromboembolic events. I equate the risk to that of birth control pills."

Raloxifene joins tamoxifen as the only other proved drug with Food and Drug Administration approval for primary breast cancer chemoprevention. The NSABP STAR (Study of Tamoxifen and Raloxifene) trial showed that the two medications are equivalent for prevention of invasive breast cancer, but that raloxifene is less effective in preventing ductal carcinoma in situ (JAMA 2006;295:2727-41). For this reason, Dr. Diamond and her colleagues don’t use it.

For postmenopausal women who are candidates for primary chemoprevention, Dr. Diamond said that she turns to exemestane on the basis of the National Cancer Institute of Canada CTG MAP-3 trial, which showed a 65% reduction in the annual incidence of breast cancer with 5 years of the aromatase inhibitor, compared with placebo. (N. Engl. J. Med. 2011;364:2381-91).

The number needed to treat with exemestane at 25 mg/day for 5 years in order to prevent one invasive breast cancer was 94 in 3 years and 26 in 5 years.

"I would argue that this is a really low NNT, and a lot of patients in your practice probably would fall into the category of qualifying for the MAP-3 study," Dr. Diamond said.

There were no serious risks associated with exemestane in MAP-3. Hot flashes and other menopausal symptoms were more common than with placebo, yet reassuringly there was no difference between the exemestane and control groups on quality of life measures.

Bone mineral density decreased over time in the exemestane group; however, patients on the aromatase inhibitor had no increased risk of fractures. Dr. Diamond advised monitoring bone density in exemestane-treated women, and if it drops significantly, consider prescribing denosumab as a subcutaneous injection once every 6 months. Denosumab is already FDA approved to increase bone mass in patients on adjuvant aromatase inhibitor therapy for breast cancer.

Dr. Diamond reported having no financial conflicts.

ESTES PARK, COLO. – Primary care physicians are uniquely positioned to help their younger adult female patients who have a history of thoracic radiation therapy for lymphoma by arranging for them to begin undergoing annual screening breast MRI, Dr. Jennifer R. Diamond said.

"That mantle cell radiation includes the upper inner quadrants of both breasts; those patients are at extremely high risk for developing breast cancer," explained Dr. Diamond, a medical oncologist at the University of Colorado, Aurora. "Many times, they’re no longer being followed by their oncologist, and it’s up to their primary care physician to pull the trigger and order the test."

Many patients likely wouldn’t know that they should do breast cancer screening at such an early age, she added, because breast cancer wasn’t an anticipated outcome back when they had their radiotherapy.

National Comprehensive Cancer Network guidelines call for annual breast MRI and mammography along with clinical breast exams every 6-12 months, beginning 8-10 years after thoracic radiotherapy or at age 25 years, whichever occurs later. Dr. Diamond typically has patients stagger the two imaging modalities 6 months apart.

Both annual breast MRI and mammography are necessary. Screening MRI is far more sensitive than mammography alone in high-risk women, and it leads to cancer diagnosis at an earlier stage. However, MRI can miss ductal carcinoma in situ that would be evident as abnormal calcifications on screening mammography, she continued.

Annual breast MRI, in addition to mammography, is also indicated for women at high breast cancer risk as defined by a lifetime estimated risk in excess of 20%, or because they possess a BRCA 1 or 2 mutation, according to the NCCN. Dr. Diamond recommended BRCAPRO as a very useful tool for estimating the lifetime risk of breast cancer in women with no previous breast cancer.

In response to an audience question, she said she’s had no problem in getting insurers to pay for annual breast MRI to supplement annual mammography, so long as she clearly documents in her note that the patient has a greater than 20% lifetime estimated risk of breast cancer.

"They won’t cover it even a week earlier than annually, though," Dr. Diamond added.

She is a big fan of breast tomosynthesis, also known as three-dimensional mammography. The Food and Drug Administration–licensed technology produces a 3-D view of the breast tissue in addition to the standard two-dimensional images, all obtained in one compression with only about 2 seconds of additional compression time. Studies have shown that this tool substantially reduces patient recall rates for nondefinitive mammograms, Dr. Diamond said.

"It allows the mammographer to scroll through the breast, looking up and down sort of like with a CT scan, but without the same radiation exposure," she explained. "It’s a really great new technology, and I think most mammography centers will increasingly turn to it."

Dr. Diamond reported having no financial conflicts.

ESTES PARK, COLO. – Primary care physicians are uniquely positioned to help their younger adult female patients who have a history of thoracic radiation therapy for lymphoma by arranging for them to begin undergoing annual screening breast MRI, Dr. Jennifer R. Diamond said.

"That mantle cell radiation includes the upper inner quadrants of both breasts; those patients are at extremely high risk for developing breast cancer," explained Dr. Diamond, a medical oncologist at the University of Colorado, Aurora. "Many times, they’re no longer being followed by their oncologist, and it’s up to their primary care physician to pull the trigger and order the test."

Many patients likely wouldn’t know that they should do breast cancer screening at such an early age, she added, because breast cancer wasn’t an anticipated outcome back when they had their radiotherapy.

National Comprehensive Cancer Network guidelines call for annual breast MRI and mammography along with clinical breast exams every 6-12 months, beginning 8-10 years after thoracic radiotherapy or at age 25 years, whichever occurs later. Dr. Diamond typically has patients stagger the two imaging modalities 6 months apart.

Both annual breast MRI and mammography are necessary. Screening MRI is far more sensitive than mammography alone in high-risk women, and it leads to cancer diagnosis at an earlier stage. However, MRI can miss ductal carcinoma in situ that would be evident as abnormal calcifications on screening mammography, she continued.

Annual breast MRI, in addition to mammography, is also indicated for women at high breast cancer risk as defined by a lifetime estimated risk in excess of 20%, or because they possess a BRCA 1 or 2 mutation, according to the NCCN. Dr. Diamond recommended BRCAPRO as a very useful tool for estimating the lifetime risk of breast cancer in women with no previous breast cancer.

In response to an audience question, she said she’s had no problem in getting insurers to pay for annual breast MRI to supplement annual mammography, so long as she clearly documents in her note that the patient has a greater than 20% lifetime estimated risk of breast cancer.

"They won’t cover it even a week earlier than annually, though," Dr. Diamond added.

She is a big fan of breast tomosynthesis, also known as three-dimensional mammography. The Food and Drug Administration–licensed technology produces a 3-D view of the breast tissue in addition to the standard two-dimensional images, all obtained in one compression with only about 2 seconds of additional compression time. Studies have shown that this tool substantially reduces patient recall rates for nondefinitive mammograms, Dr. Diamond said.

"It allows the mammographer to scroll through the breast, looking up and down sort of like with a CT scan, but without the same radiation exposure," she explained. "It’s a really great new technology, and I think most mammography centers will increasingly turn to it."

Dr. Diamond reported having no financial conflicts.

ESTES PARK, COLO. – Primary care physicians are uniquely positioned to help their younger adult female patients who have a history of thoracic radiation therapy for lymphoma by arranging for them to begin undergoing annual screening breast MRI, Dr. Jennifer R. Diamond said.

"That mantle cell radiation includes the upper inner quadrants of both breasts; those patients are at extremely high risk for developing breast cancer," explained Dr. Diamond, a medical oncologist at the University of Colorado, Aurora. "Many times, they’re no longer being followed by their oncologist, and it’s up to their primary care physician to pull the trigger and order the test."

Many patients likely wouldn’t know that they should do breast cancer screening at such an early age, she added, because breast cancer wasn’t an anticipated outcome back when they had their radiotherapy.

National Comprehensive Cancer Network guidelines call for annual breast MRI and mammography along with clinical breast exams every 6-12 months, beginning 8-10 years after thoracic radiotherapy or at age 25 years, whichever occurs later. Dr. Diamond typically has patients stagger the two imaging modalities 6 months apart.

Both annual breast MRI and mammography are necessary. Screening MRI is far more sensitive than mammography alone in high-risk women, and it leads to cancer diagnosis at an earlier stage. However, MRI can miss ductal carcinoma in situ that would be evident as abnormal calcifications on screening mammography, she continued.

Annual breast MRI, in addition to mammography, is also indicated for women at high breast cancer risk as defined by a lifetime estimated risk in excess of 20%, or because they possess a BRCA 1 or 2 mutation, according to the NCCN. Dr. Diamond recommended BRCAPRO as a very useful tool for estimating the lifetime risk of breast cancer in women with no previous breast cancer.

In response to an audience question, she said she’s had no problem in getting insurers to pay for annual breast MRI to supplement annual mammography, so long as she clearly documents in her note that the patient has a greater than 20% lifetime estimated risk of breast cancer.

"They won’t cover it even a week earlier than annually, though," Dr. Diamond added.

She is a big fan of breast tomosynthesis, also known as three-dimensional mammography. The Food and Drug Administration–licensed technology produces a 3-D view of the breast tissue in addition to the standard two-dimensional images, all obtained in one compression with only about 2 seconds of additional compression time. Studies have shown that this tool substantially reduces patient recall rates for nondefinitive mammograms, Dr. Diamond said.

"It allows the mammographer to scroll through the breast, looking up and down sort of like with a CT scan, but without the same radiation exposure," she explained. "It’s a really great new technology, and I think most mammography centers will increasingly turn to it."

Dr. Diamond reported having no financial conflicts.