Michele G. Sullivan

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die of all-cause mortality over a 2-year period than were those who did not take the drug. The association remained significant even after researchers controlled for age and sex, and after factoring in several baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the meeting. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery, or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis.

Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 mg/dL vs. 131 mg/dL), and higher systolic blood pressure (138 mm Hg vs. 136 mm Hg).

Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for sex and age only, metformin was associated with a 33% reduction in the risk of all-cause death.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death. When the researchers examined the sexes separately, they found no statistically significant differences.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%) and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing heart failure, conferring a significant 31% reduction in the risk of death.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio, 0.64 vs. 0.80).

The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die of all-cause mortality over a 2-year period than were those who did not take the drug. The association remained significant even after researchers controlled for age and sex, and after factoring in several baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the meeting. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery, or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis.

Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 mg/dL vs. 131 mg/dL), and higher systolic blood pressure (138 mm Hg vs. 136 mm Hg).

Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for sex and age only, metformin was associated with a 33% reduction in the risk of all-cause death.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death. When the researchers examined the sexes separately, they found no statistically significant differences.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%) and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing heart failure, conferring a significant 31% reduction in the risk of death.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio, 0.64 vs. 0.80).

The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die of all-cause mortality over a 2-year period than were those who did not take the drug. The association remained significant even after researchers controlled for age and sex, and after factoring in several baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the meeting. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery, or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis.

Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 mg/dL vs. 131 mg/dL), and higher systolic blood pressure (138 mm Hg vs. 136 mm Hg).

Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for sex and age only, metformin was associated with a 33% reduction in the risk of all-cause death.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death. When the researchers examined the sexes separately, they found no statistically significant differences.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%) and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing heart failure, conferring a significant 31% reduction in the risk of death.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio, 0.64 vs. 0.80).

The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

PARIS – Low-dose radioiodine ablation of 1.1 gigabecquerels (GBqs) is just as effective as the standard 3.7 GBq dose in eradicating thyroid remnants, with or without the concomitant use of recombinant human thyroid-stimulating hormone, in patients who have undergone thyroidectomy for differentiated thyroid cancer.

Two international randomized, controlled trials presented Sept. 13 at the International Thyroid Congress reached the same conclusion: Ablation rates were virtually identical between the two radioiodine doses. The findings should “change medical practice in the [United States], and around the world,” said Dr. Ernest Mazzaferri, professor emeritus of medicine at Ohio State University, Columbus.

“Today, we learned of two studies that will change the impact of how this disease is treated, by using very small amounts of radiation,” he said in an interview. “These robust studies will change practice – as they should – and are a strong argument to treat with a low amount of radiation. It’s better for the patients, and it works.”

The two trials, ESTIMABL from France and the British HiLo trial, encompassed almost 1,200 patients with differentiated thyroid cancer who had undergone a complete thyroidectomy and were ready for radioiodine ablation. Both were multifactorial studies that compared the 1.1- and 3.7-GBq doses with and without the use of recombinant human thyroid stimulating hormone.

Dr. Bogdan Catargi of the Centre Hospitalier Universities, Bordeaux, presented the ESTIMABL results. The phase III study randomized 753 patients to four strategies for postoperative radioiodine ablation in a multifactorial design: a method of thyroid stimulating (TSH) stimulation (either thyroid hormone withdrawal or continuation) and a method of radioiodine ablation (1.1 GBq or 3.7 GBq). Full follow-up data were available for 542 of the group.

The patients were a mean of 49 years old; they had undergone total thyroidectomy for differentiated papillary or follicular thyroid cancer 1-3 months prior. Most (90%) had papillary cancer. Patients with aggressive histology were not included in the trial.

Thyroid ablation was determined 6-10 months after treatment with recombinant human thyroid stimulating hormone (rhTSH), stimulated thyroglobulin, and neck ultrasound.

At final follow-up, ablation rates were not significantly different among any of the four groups. In the group retaining rhTSH and treated with 1.1 GBq, the rate was 89%; in those on rhTSH treated at 3.7 GBq, the ablation rate was 89%. Among those treated with the low dose whose rhTSH was withdrawn, ablation was complete in 92%. The rate of ablation was 93% in that group treated with the higher-radiation dose.

None of the between-group differences were significant, Dr. Catargi said. “When comparing the four groups, we saw no difference between them in terms of either the stimulation method or radioiodine dose,” he said. “This is a major finding, showing for the first time the equivalence of these four strategies.”

If the finding holds up in the final analysis, “It validates the use of recombinant TSH and low radioiodine for these low-risk patients,” he said.

Dr. Ujjal K. Mallick of the Freeman Hospital, Newcastle upon Tyne, U.K., presented the HiLo trial results. Similar in design to ESTIMABL, this study randomized 438 patients who had undergone thyroidectomy to either 1.1 GBq or 3.7 GBq and either rhTSH or thyroid hormone withdrawal. Dr. Mallick presented preliminary data on 258 patients who had completed the 9-month follow-up period.

All patients were put on a low-iodine diet and had a pre-ablation scan to assess remnant size. Ablation success was determined 6-9 months later using an I-131 iodide diagnostic scan.

Again, Dr. Mallick said, all of the treatment combinations were similarly effective. Ablation rates ranged from 93% to 95%. Subgroup analyses also found no difference between withdrawing or continuing rhTSH, and radioiodine dose. There were also no significant differences when the group was examined by tumor stage or nodal involvement. “The conclusion we can draw is that 1.1 GBq with rhTSH has a similar ablation rate to rhTSh withdrawal with the 3.7 GBq radioiodine,” he said.

HiLo also examined quality of life in its patients and found that patients who had the lower radioiodine dosage left the hospital earlier and missed fewer days of work, “raising the idea that this can be a single-day procedure,” Dr. Mallick said. Patients who stayed on their thyroid hormone, however, felt better and were able to accomplish more at home and at work than were those whose hormone was withdrawn.

“We can now say that patients with thyroid cancer staged at T1-T3 and favorable histology can be as successfully treated with 1.1 GBq as they can with 3.7, and that rhTSH continuation or withdrawal does not affect ablation.”

HiLo was sponsored by Cancer Research U.K.; Dr. Mallick disclosed that he is a consultant for Genzyme Corp., which provided the rhTSH for the study. ESTIMABL was funded by the French Institute National du Cancer; Dr. Catargi did not mention any financial disclosures.

PARIS – Low-dose radioiodine ablation of 1.1 gigabecquerels (GBqs) is just as effective as the standard 3.7 GBq dose in eradicating thyroid remnants, with or without the concomitant use of recombinant human thyroid-stimulating hormone, in patients who have undergone thyroidectomy for differentiated thyroid cancer.

Two international randomized, controlled trials presented Sept. 13 at the International Thyroid Congress reached the same conclusion: Ablation rates were virtually identical between the two radioiodine doses. The findings should “change medical practice in the [United States], and around the world,” said Dr. Ernest Mazzaferri, professor emeritus of medicine at Ohio State University, Columbus.

“Today, we learned of two studies that will change the impact of how this disease is treated, by using very small amounts of radiation,” he said in an interview. “These robust studies will change practice – as they should – and are a strong argument to treat with a low amount of radiation. It’s better for the patients, and it works.”

The two trials, ESTIMABL from France and the British HiLo trial, encompassed almost 1,200 patients with differentiated thyroid cancer who had undergone a complete thyroidectomy and were ready for radioiodine ablation. Both were multifactorial studies that compared the 1.1- and 3.7-GBq doses with and without the use of recombinant human thyroid stimulating hormone.

Dr. Bogdan Catargi of the Centre Hospitalier Universities, Bordeaux, presented the ESTIMABL results. The phase III study randomized 753 patients to four strategies for postoperative radioiodine ablation in a multifactorial design: a method of thyroid stimulating (TSH) stimulation (either thyroid hormone withdrawal or continuation) and a method of radioiodine ablation (1.1 GBq or 3.7 GBq). Full follow-up data were available for 542 of the group.

The patients were a mean of 49 years old; they had undergone total thyroidectomy for differentiated papillary or follicular thyroid cancer 1-3 months prior. Most (90%) had papillary cancer. Patients with aggressive histology were not included in the trial.

Thyroid ablation was determined 6-10 months after treatment with recombinant human thyroid stimulating hormone (rhTSH), stimulated thyroglobulin, and neck ultrasound.

At final follow-up, ablation rates were not significantly different among any of the four groups. In the group retaining rhTSH and treated with 1.1 GBq, the rate was 89%; in those on rhTSH treated at 3.7 GBq, the ablation rate was 89%. Among those treated with the low dose whose rhTSH was withdrawn, ablation was complete in 92%. The rate of ablation was 93% in that group treated with the higher-radiation dose.

None of the between-group differences were significant, Dr. Catargi said. “When comparing the four groups, we saw no difference between them in terms of either the stimulation method or radioiodine dose,” he said. “This is a major finding, showing for the first time the equivalence of these four strategies.”

If the finding holds up in the final analysis, “It validates the use of recombinant TSH and low radioiodine for these low-risk patients,” he said.

Dr. Ujjal K. Mallick of the Freeman Hospital, Newcastle upon Tyne, U.K., presented the HiLo trial results. Similar in design to ESTIMABL, this study randomized 438 patients who had undergone thyroidectomy to either 1.1 GBq or 3.7 GBq and either rhTSH or thyroid hormone withdrawal. Dr. Mallick presented preliminary data on 258 patients who had completed the 9-month follow-up period.

All patients were put on a low-iodine diet and had a pre-ablation scan to assess remnant size. Ablation success was determined 6-9 months later using an I-131 iodide diagnostic scan.

Again, Dr. Mallick said, all of the treatment combinations were similarly effective. Ablation rates ranged from 93% to 95%. Subgroup analyses also found no difference between withdrawing or continuing rhTSH, and radioiodine dose. There were also no significant differences when the group was examined by tumor stage or nodal involvement. “The conclusion we can draw is that 1.1 GBq with rhTSH has a similar ablation rate to rhTSh withdrawal with the 3.7 GBq radioiodine,” he said.

HiLo also examined quality of life in its patients and found that patients who had the lower radioiodine dosage left the hospital earlier and missed fewer days of work, “raising the idea that this can be a single-day procedure,” Dr. Mallick said. Patients who stayed on their thyroid hormone, however, felt better and were able to accomplish more at home and at work than were those whose hormone was withdrawn.

“We can now say that patients with thyroid cancer staged at T1-T3 and favorable histology can be as successfully treated with 1.1 GBq as they can with 3.7, and that rhTSH continuation or withdrawal does not affect ablation.”

HiLo was sponsored by Cancer Research U.K.; Dr. Mallick disclosed that he is a consultant for Genzyme Corp., which provided the rhTSH for the study. ESTIMABL was funded by the French Institute National du Cancer; Dr. Catargi did not mention any financial disclosures.

PARIS – Low-dose radioiodine ablation of 1.1 gigabecquerels (GBqs) is just as effective as the standard 3.7 GBq dose in eradicating thyroid remnants, with or without the concomitant use of recombinant human thyroid-stimulating hormone, in patients who have undergone thyroidectomy for differentiated thyroid cancer.

Two international randomized, controlled trials presented Sept. 13 at the International Thyroid Congress reached the same conclusion: Ablation rates were virtually identical between the two radioiodine doses. The findings should “change medical practice in the [United States], and around the world,” said Dr. Ernest Mazzaferri, professor emeritus of medicine at Ohio State University, Columbus.

“Today, we learned of two studies that will change the impact of how this disease is treated, by using very small amounts of radiation,” he said in an interview. “These robust studies will change practice – as they should – and are a strong argument to treat with a low amount of radiation. It’s better for the patients, and it works.”

The two trials, ESTIMABL from France and the British HiLo trial, encompassed almost 1,200 patients with differentiated thyroid cancer who had undergone a complete thyroidectomy and were ready for radioiodine ablation. Both were multifactorial studies that compared the 1.1- and 3.7-GBq doses with and without the use of recombinant human thyroid stimulating hormone.

Dr. Bogdan Catargi of the Centre Hospitalier Universities, Bordeaux, presented the ESTIMABL results. The phase III study randomized 753 patients to four strategies for postoperative radioiodine ablation in a multifactorial design: a method of thyroid stimulating (TSH) stimulation (either thyroid hormone withdrawal or continuation) and a method of radioiodine ablation (1.1 GBq or 3.7 GBq). Full follow-up data were available for 542 of the group.

The patients were a mean of 49 years old; they had undergone total thyroidectomy for differentiated papillary or follicular thyroid cancer 1-3 months prior. Most (90%) had papillary cancer. Patients with aggressive histology were not included in the trial.

Thyroid ablation was determined 6-10 months after treatment with recombinant human thyroid stimulating hormone (rhTSH), stimulated thyroglobulin, and neck ultrasound.

At final follow-up, ablation rates were not significantly different among any of the four groups. In the group retaining rhTSH and treated with 1.1 GBq, the rate was 89%; in those on rhTSH treated at 3.7 GBq, the ablation rate was 89%. Among those treated with the low dose whose rhTSH was withdrawn, ablation was complete in 92%. The rate of ablation was 93% in that group treated with the higher-radiation dose.

None of the between-group differences were significant, Dr. Catargi said. “When comparing the four groups, we saw no difference between them in terms of either the stimulation method or radioiodine dose,” he said. “This is a major finding, showing for the first time the equivalence of these four strategies.”

If the finding holds up in the final analysis, “It validates the use of recombinant TSH and low radioiodine for these low-risk patients,” he said.

Dr. Ujjal K. Mallick of the Freeman Hospital, Newcastle upon Tyne, U.K., presented the HiLo trial results. Similar in design to ESTIMABL, this study randomized 438 patients who had undergone thyroidectomy to either 1.1 GBq or 3.7 GBq and either rhTSH or thyroid hormone withdrawal. Dr. Mallick presented preliminary data on 258 patients who had completed the 9-month follow-up period.

All patients were put on a low-iodine diet and had a pre-ablation scan to assess remnant size. Ablation success was determined 6-9 months later using an I-131 iodide diagnostic scan.

Again, Dr. Mallick said, all of the treatment combinations were similarly effective. Ablation rates ranged from 93% to 95%. Subgroup analyses also found no difference between withdrawing or continuing rhTSH, and radioiodine dose. There were also no significant differences when the group was examined by tumor stage or nodal involvement. “The conclusion we can draw is that 1.1 GBq with rhTSH has a similar ablation rate to rhTSh withdrawal with the 3.7 GBq radioiodine,” he said.

HiLo also examined quality of life in its patients and found that patients who had the lower radioiodine dosage left the hospital earlier and missed fewer days of work, “raising the idea that this can be a single-day procedure,” Dr. Mallick said. Patients who stayed on their thyroid hormone, however, felt better and were able to accomplish more at home and at work than were those whose hormone was withdrawn.

“We can now say that patients with thyroid cancer staged at T1-T3 and favorable histology can be as successfully treated with 1.1 GBq as they can with 3.7, and that rhTSH continuation or withdrawal does not affect ablation.”

HiLo was sponsored by Cancer Research U.K.; Dr. Mallick disclosed that he is a consultant for Genzyme Corp., which provided the rhTSH for the study. ESTIMABL was funded by the French Institute National du Cancer; Dr. Catargi did not mention any financial disclosures.

VALENCIA, Spain - Children with localized scleroderma responded better to methotrexate than to prednisone in a small, placebo-controlled trial.

“Although localized scleroderma is rather rare, it can be very aggressive and lead to complications in some patients,” Dr. Francesco Zulian said at the 17th Pediatric Rheumatology European Society Congress. “Some patients can have psychological sequelae as well, if the lesions occur on the face.”

Dr. Zulian described his 12-month study, dubbed the INSIEME Project. An Italian study, the double-blind placebo-controlled trial compared two therapeutic strategies - prednisone alone and prednisone plus methotrexate – for the treatment of juvenile localized scleroderma (JLS). This project involved 21 Italian pediatric rheumatology and dermatology centers.

The study evaluated 70 patients (mean age, 10 years) who had a mean disease duration of 2 years and a mean disease onset of 7 years. All had active disease for at least 6 months, and none had been exposed to immunosuppressant therapy for 6 months before enrollment.

Of these, 46 were randomized to receive methotrexate (15 mg/m2; maximum dose, 20 mg) once a week plus daily oral prednisone (1 mg/kg per day; maximum, 50 mg). The control group took a weekly placebo plus the daily prednisone. In both groups, the prednisone was tapered after 3 months, with a complete cessation by month 4. Treatment with methotrexate or placebo was continued for 12 months or to the time of a flare.

The investigators measured the size of existing lesions, noted any new lesions, and measured skin temperature to evaluate response. “Skin lesions were evaluated by a computerized scoring system; changes were quantified by the skin score rate [SSR]. Clinical examinations and series thermography monitored the changes in active lesions,” said Dr. Zulian of the University of Padua (Italy).

Treatment response was the primary end point. Responders were defined as those who achieved an SSR of less than 1, a decrease in lesion temperature of at least 10% compared with baseline, and no new lesions during treatment.

Relapse was defined as an SSR of more than 1, unchanged or increased lesion temperature, or the appearance of new lesions.

In phase 1 (0-3 months), all of the patients were taking prednisone, plus either methotrexate or placebo. “During this time, the skin score rate indicated a similar, good response in both groups,” Dr. Zulian said. But from 6 to 9 months, after the prednisone taper was complete, significantly more flares began to appear in the control group (71% vs. 33%). This led to a large dropout rate in the placebo group, with only 7 of the original 24 completing the trial. However, “there was a consistent response in the methotrexate groups,” Dr. Zulian noted.

The mean skin score rate decreased from 1 to 0.79 in the methotrexate group, but did not change in the placebo group. The mean temperature of the target lesion decreased by 44% in the methotrexate group and 12% in the placebo group - a significant difference. New lesions appeared in 6.5% of the patients taking methotrexate and 17% of those taking placebo, also significantly different.

After 12 months, there were significantly more responders in the methotrexate than the placebo groups (67% vs. 29%).

Mild side effects occurred in 56% of the methotrexate group and 46% of the placebo group, but none were serious enough to stop treatment, Dr. Zulian added. “The methotrexate was well tolerated and effective.”

VALENCIA, Spain - Children with localized scleroderma responded better to methotrexate than to prednisone in a small, placebo-controlled trial.

“Although localized scleroderma is rather rare, it can be very aggressive and lead to complications in some patients,” Dr. Francesco Zulian said at the 17th Pediatric Rheumatology European Society Congress. “Some patients can have psychological sequelae as well, if the lesions occur on the face.”

Dr. Zulian described his 12-month study, dubbed the INSIEME Project. An Italian study, the double-blind placebo-controlled trial compared two therapeutic strategies - prednisone alone and prednisone plus methotrexate – for the treatment of juvenile localized scleroderma (JLS). This project involved 21 Italian pediatric rheumatology and dermatology centers.

The study evaluated 70 patients (mean age, 10 years) who had a mean disease duration of 2 years and a mean disease onset of 7 years. All had active disease for at least 6 months, and none had been exposed to immunosuppressant therapy for 6 months before enrollment.

Of these, 46 were randomized to receive methotrexate (15 mg/m2; maximum dose, 20 mg) once a week plus daily oral prednisone (1 mg/kg per day; maximum, 50 mg). The control group took a weekly placebo plus the daily prednisone. In both groups, the prednisone was tapered after 3 months, with a complete cessation by month 4. Treatment with methotrexate or placebo was continued for 12 months or to the time of a flare.

The investigators measured the size of existing lesions, noted any new lesions, and measured skin temperature to evaluate response. “Skin lesions were evaluated by a computerized scoring system; changes were quantified by the skin score rate [SSR]. Clinical examinations and series thermography monitored the changes in active lesions,” said Dr. Zulian of the University of Padua (Italy).

Treatment response was the primary end point. Responders were defined as those who achieved an SSR of less than 1, a decrease in lesion temperature of at least 10% compared with baseline, and no new lesions during treatment.

Relapse was defined as an SSR of more than 1, unchanged or increased lesion temperature, or the appearance of new lesions.

In phase 1 (0-3 months), all of the patients were taking prednisone, plus either methotrexate or placebo. “During this time, the skin score rate indicated a similar, good response in both groups,” Dr. Zulian said. But from 6 to 9 months, after the prednisone taper was complete, significantly more flares began to appear in the control group (71% vs. 33%). This led to a large dropout rate in the placebo group, with only 7 of the original 24 completing the trial. However, “there was a consistent response in the methotrexate groups,” Dr. Zulian noted.

The mean skin score rate decreased from 1 to 0.79 in the methotrexate group, but did not change in the placebo group. The mean temperature of the target lesion decreased by 44% in the methotrexate group and 12% in the placebo group - a significant difference. New lesions appeared in 6.5% of the patients taking methotrexate and 17% of those taking placebo, also significantly different.

After 12 months, there were significantly more responders in the methotrexate than the placebo groups (67% vs. 29%).

Mild side effects occurred in 56% of the methotrexate group and 46% of the placebo group, but none were serious enough to stop treatment, Dr. Zulian added. “The methotrexate was well tolerated and effective.”

VALENCIA, Spain - Children with localized scleroderma responded better to methotrexate than to prednisone in a small, placebo-controlled trial.

“Although localized scleroderma is rather rare, it can be very aggressive and lead to complications in some patients,” Dr. Francesco Zulian said at the 17th Pediatric Rheumatology European Society Congress. “Some patients can have psychological sequelae as well, if the lesions occur on the face.”

Dr. Zulian described his 12-month study, dubbed the INSIEME Project. An Italian study, the double-blind placebo-controlled trial compared two therapeutic strategies - prednisone alone and prednisone plus methotrexate – for the treatment of juvenile localized scleroderma (JLS). This project involved 21 Italian pediatric rheumatology and dermatology centers.

The study evaluated 70 patients (mean age, 10 years) who had a mean disease duration of 2 years and a mean disease onset of 7 years. All had active disease for at least 6 months, and none had been exposed to immunosuppressant therapy for 6 months before enrollment.

Of these, 46 were randomized to receive methotrexate (15 mg/m2; maximum dose, 20 mg) once a week plus daily oral prednisone (1 mg/kg per day; maximum, 50 mg). The control group took a weekly placebo plus the daily prednisone. In both groups, the prednisone was tapered after 3 months, with a complete cessation by month 4. Treatment with methotrexate or placebo was continued for 12 months or to the time of a flare.

The investigators measured the size of existing lesions, noted any new lesions, and measured skin temperature to evaluate response. “Skin lesions were evaluated by a computerized scoring system; changes were quantified by the skin score rate [SSR]. Clinical examinations and series thermography monitored the changes in active lesions,” said Dr. Zulian of the University of Padua (Italy).

Treatment response was the primary end point. Responders were defined as those who achieved an SSR of less than 1, a decrease in lesion temperature of at least 10% compared with baseline, and no new lesions during treatment.

Relapse was defined as an SSR of more than 1, unchanged or increased lesion temperature, or the appearance of new lesions.

In phase 1 (0-3 months), all of the patients were taking prednisone, plus either methotrexate or placebo. “During this time, the skin score rate indicated a similar, good response in both groups,” Dr. Zulian said. But from 6 to 9 months, after the prednisone taper was complete, significantly more flares began to appear in the control group (71% vs. 33%). This led to a large dropout rate in the placebo group, with only 7 of the original 24 completing the trial. However, “there was a consistent response in the methotrexate groups,” Dr. Zulian noted.

The mean skin score rate decreased from 1 to 0.79 in the methotrexate group, but did not change in the placebo group. The mean temperature of the target lesion decreased by 44% in the methotrexate group and 12% in the placebo group - a significant difference. New lesions appeared in 6.5% of the patients taking methotrexate and 17% of those taking placebo, also significantly different.

After 12 months, there were significantly more responders in the methotrexate than the placebo groups (67% vs. 29%).

Mild side effects occurred in 56% of the methotrexate group and 46% of the placebo group, but none were serious enough to stop treatment, Dr. Zulian added. “The methotrexate was well tolerated and effective.”

CHICAGO - Adalimumab was well tolerated, with a low incidence of adverse events and serious infections, in two studies totaling almost 1,800 patients who took the drug for up to 5 years.

The first study was a meta-analysis of 11 global clinical trials, totaling almost 1,721 patients. All of the phase II or III studies included safety data analyzed in 2007 and 2008, according to a report by Dr. Richard Langley and his associates presented at the summer meeting of the American Academy of Dermatology.

The drug was administered subcutaneously in all treatment groups. Dosing regimens included 80 mg/week initially, followed by 40 mg every other week (1,039 patients were on this regimen); 40 mg every other week (422 were on this regimen); 80 mg for the first 2 weeks, followed by 40 mg every other week (198 patients were on this regimen); and 80 mg every other week (62 patients).

All patients were about 44 years old, with disease duration of 18 years. The percentage of body involved was 27%; psoriatic arthritis was present in 28%, according to Dr. Langley of Dalhousie University, Halifax.

The length of adalimumab exposure ranged from 48 weeks to 5.5 years; the mean exposure time was 2 years. At both the 2007 and 2008 safety analyses, the overall rate of adverse events was 3 events per person-year.

The most commonly reported were nasopharyngitis, upper respiratory infection, and sinusitis, which accounted for 47% of the 3,489 infectious adverse events (AEs) reported.

In the 2008 analysis, 60 serious AEs were reported in 50 patients. There were two occurrences of sepsis; the incidence rates of pneumonia were 0.002 per person-year; limb abscess occurred at a rate of 0.001 abscess per person-year; and other serious infections, less than 0.001 per person-year.

Tuberculin skin tests were positive in 138 patients in the 6% of patients who received a test at baseline. There were no cases of latent TB reactivation in those who complied with prophylactic treatment. Six patients developed tuberculosis; four of them were Asian males.

Twelve opportunistic infections occurred in 11 patients; none was considered serious. The infections included 11 cases of candidiasis and 1 case of coccidioidomycosis, which occurred in the southwestern United States where the disease is endemic.

The second study examined efficacy and adverse event rates in patients who took adalimumab for moderate-severe plaque psoriasis of the hands and feet. These 72 patients were included in a single 28-week randomized, placebo-controlled crossover trial.

The patients' mean age was 50 years. The duration of psoriasis was about 12 years; the duration of hand/feet psoriasis, about 8 years.

The crossover trial randomized 49 patients to 40 mg adalimumab every other week and 23 to placebo for 16 weeks; after that, an open-label extension trial included all patients taking 30 mg every other week.

At week 16, significantly more of the adalimumab-treated patients reported being clear or almost clear of their plaque lesions, compared with placebo (31% vs. 4%). At weeks 16 and 28 of the trial, 51% of the active group and 47% of the crossover group reported scores of clear or almost clear.

During the first 16 weeks, adverse events occurred in 63% of the active group and 70% of the placebo group. Serious adverse events occurred in none of the active group and 4% of the placebo group. Infectious AEs occurred in 35% of the active group and 44% of the placebo group. One malignancy occurred in the placebo group.

There was one opportunistic infection in the active group. Hepatic events occurred in one patient in the adalimumab group.

During the crossover phase, AEs occurred in 43% of the adalimumab group and 39% of the crossover group; the most commonly reported were nasopharyngitis, headache, diarrhea, and infection site reaction.

AEs were considered serious in two adalimumab patients. Infectious adverse events occurred in 24% of the adalimumab group and 17% of the crossover group. There was one case of heart failure in the adalimumab group.

Three adalimumab patients and two crossover patients discontinued treatment because of the AEs. There were no deaths, serious infections, cases of tuberculosis, demyelinating diseases, lupus-like syndromes, lymphomas, or non-melanoma skins cancers reported.

Disclosures: All of the studies were supported by Abbott Laboratories. Dr. Langley disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Isotechnika, LEO Pharma, NanoBio, Novartis, Pfizer, Schering, and Serono.

CHICAGO - Adalimumab was well tolerated, with a low incidence of adverse events and serious infections, in two studies totaling almost 1,800 patients who took the drug for up to 5 years.

The first study was a meta-analysis of 11 global clinical trials, totaling almost 1,721 patients. All of the phase II or III studies included safety data analyzed in 2007 and 2008, according to a report by Dr. Richard Langley and his associates presented at the summer meeting of the American Academy of Dermatology.

The drug was administered subcutaneously in all treatment groups. Dosing regimens included 80 mg/week initially, followed by 40 mg every other week (1,039 patients were on this regimen); 40 mg every other week (422 were on this regimen); 80 mg for the first 2 weeks, followed by 40 mg every other week (198 patients were on this regimen); and 80 mg every other week (62 patients).

All patients were about 44 years old, with disease duration of 18 years. The percentage of body involved was 27%; psoriatic arthritis was present in 28%, according to Dr. Langley of Dalhousie University, Halifax.

The length of adalimumab exposure ranged from 48 weeks to 5.5 years; the mean exposure time was 2 years. At both the 2007 and 2008 safety analyses, the overall rate of adverse events was 3 events per person-year.

The most commonly reported were nasopharyngitis, upper respiratory infection, and sinusitis, which accounted for 47% of the 3,489 infectious adverse events (AEs) reported.

In the 2008 analysis, 60 serious AEs were reported in 50 patients. There were two occurrences of sepsis; the incidence rates of pneumonia were 0.002 per person-year; limb abscess occurred at a rate of 0.001 abscess per person-year; and other serious infections, less than 0.001 per person-year.

Tuberculin skin tests were positive in 138 patients in the 6% of patients who received a test at baseline. There were no cases of latent TB reactivation in those who complied with prophylactic treatment. Six patients developed tuberculosis; four of them were Asian males.

Twelve opportunistic infections occurred in 11 patients; none was considered serious. The infections included 11 cases of candidiasis and 1 case of coccidioidomycosis, which occurred in the southwestern United States where the disease is endemic.

The second study examined efficacy and adverse event rates in patients who took adalimumab for moderate-severe plaque psoriasis of the hands and feet. These 72 patients were included in a single 28-week randomized, placebo-controlled crossover trial.

The patients' mean age was 50 years. The duration of psoriasis was about 12 years; the duration of hand/feet psoriasis, about 8 years.

The crossover trial randomized 49 patients to 40 mg adalimumab every other week and 23 to placebo for 16 weeks; after that, an open-label extension trial included all patients taking 30 mg every other week.

At week 16, significantly more of the adalimumab-treated patients reported being clear or almost clear of their plaque lesions, compared with placebo (31% vs. 4%). At weeks 16 and 28 of the trial, 51% of the active group and 47% of the crossover group reported scores of clear or almost clear.

During the first 16 weeks, adverse events occurred in 63% of the active group and 70% of the placebo group. Serious adverse events occurred in none of the active group and 4% of the placebo group. Infectious AEs occurred in 35% of the active group and 44% of the placebo group. One malignancy occurred in the placebo group.

There was one opportunistic infection in the active group. Hepatic events occurred in one patient in the adalimumab group.

During the crossover phase, AEs occurred in 43% of the adalimumab group and 39% of the crossover group; the most commonly reported were nasopharyngitis, headache, diarrhea, and infection site reaction.

AEs were considered serious in two adalimumab patients. Infectious adverse events occurred in 24% of the adalimumab group and 17% of the crossover group. There was one case of heart failure in the adalimumab group.

Three adalimumab patients and two crossover patients discontinued treatment because of the AEs. There were no deaths, serious infections, cases of tuberculosis, demyelinating diseases, lupus-like syndromes, lymphomas, or non-melanoma skins cancers reported.

Disclosures: All of the studies were supported by Abbott Laboratories. Dr. Langley disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Isotechnika, LEO Pharma, NanoBio, Novartis, Pfizer, Schering, and Serono.

CHICAGO - Adalimumab was well tolerated, with a low incidence of adverse events and serious infections, in two studies totaling almost 1,800 patients who took the drug for up to 5 years.

The first study was a meta-analysis of 11 global clinical trials, totaling almost 1,721 patients. All of the phase II or III studies included safety data analyzed in 2007 and 2008, according to a report by Dr. Richard Langley and his associates presented at the summer meeting of the American Academy of Dermatology.

The drug was administered subcutaneously in all treatment groups. Dosing regimens included 80 mg/week initially, followed by 40 mg every other week (1,039 patients were on this regimen); 40 mg every other week (422 were on this regimen); 80 mg for the first 2 weeks, followed by 40 mg every other week (198 patients were on this regimen); and 80 mg every other week (62 patients).

All patients were about 44 years old, with disease duration of 18 years. The percentage of body involved was 27%; psoriatic arthritis was present in 28%, according to Dr. Langley of Dalhousie University, Halifax.

The length of adalimumab exposure ranged from 48 weeks to 5.5 years; the mean exposure time was 2 years. At both the 2007 and 2008 safety analyses, the overall rate of adverse events was 3 events per person-year.

The most commonly reported were nasopharyngitis, upper respiratory infection, and sinusitis, which accounted for 47% of the 3,489 infectious adverse events (AEs) reported.

In the 2008 analysis, 60 serious AEs were reported in 50 patients. There were two occurrences of sepsis; the incidence rates of pneumonia were 0.002 per person-year; limb abscess occurred at a rate of 0.001 abscess per person-year; and other serious infections, less than 0.001 per person-year.

Tuberculin skin tests were positive in 138 patients in the 6% of patients who received a test at baseline. There were no cases of latent TB reactivation in those who complied with prophylactic treatment. Six patients developed tuberculosis; four of them were Asian males.

Twelve opportunistic infections occurred in 11 patients; none was considered serious. The infections included 11 cases of candidiasis and 1 case of coccidioidomycosis, which occurred in the southwestern United States where the disease is endemic.

The second study examined efficacy and adverse event rates in patients who took adalimumab for moderate-severe plaque psoriasis of the hands and feet. These 72 patients were included in a single 28-week randomized, placebo-controlled crossover trial.

The patients' mean age was 50 years. The duration of psoriasis was about 12 years; the duration of hand/feet psoriasis, about 8 years.

The crossover trial randomized 49 patients to 40 mg adalimumab every other week and 23 to placebo for 16 weeks; after that, an open-label extension trial included all patients taking 30 mg every other week.

At week 16, significantly more of the adalimumab-treated patients reported being clear or almost clear of their plaque lesions, compared with placebo (31% vs. 4%). At weeks 16 and 28 of the trial, 51% of the active group and 47% of the crossover group reported scores of clear or almost clear.

During the first 16 weeks, adverse events occurred in 63% of the active group and 70% of the placebo group. Serious adverse events occurred in none of the active group and 4% of the placebo group. Infectious AEs occurred in 35% of the active group and 44% of the placebo group. One malignancy occurred in the placebo group.

There was one opportunistic infection in the active group. Hepatic events occurred in one patient in the adalimumab group.

During the crossover phase, AEs occurred in 43% of the adalimumab group and 39% of the crossover group; the most commonly reported were nasopharyngitis, headache, diarrhea, and infection site reaction.

AEs were considered serious in two adalimumab patients. Infectious adverse events occurred in 24% of the adalimumab group and 17% of the crossover group. There was one case of heart failure in the adalimumab group.

Three adalimumab patients and two crossover patients discontinued treatment because of the AEs. There were no deaths, serious infections, cases of tuberculosis, demyelinating diseases, lupus-like syndromes, lymphomas, or non-melanoma skins cancers reported.

Disclosures: All of the studies were supported by Abbott Laboratories. Dr. Langley disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Isotechnika, LEO Pharma, NanoBio, Novartis, Pfizer, Schering, and Serono.

CHICAGO – Dr. Richard L. Gallo put on his Myth Busters hat at a recent dermatology meeting to debunk – and in some cases uphold – some of the most popular ideas about vitamin D.

"This subject is nothing new," noted Dr. Gallo, recounting a bit of vitamin D yore. "In 1936, Schlitz beer urged customers to drink the beverage because it contained 100 units of vitamin D, and could ward off colds and flu. So even back then, they were on to something."

But, Dr. Gallo questioned, is the idea that vitamin D can strengthen the immune system a reality – or a myth? And how about other claims touted in the public press, that sunlight is the best source of vitamin D, that the vitamin strengthen bones and protects against cancer.

"Unfortunately, vitamin D information has become something of a shell game, with positions that overstate the strength of the evidence. As dermatologists, for example, we know the carcinogenic potential of sunlight, but there are now opposing groups that advocate health by increasing vitamin D through sun exposure."

Myth No. 1: Fifteen minutes per day of sunlight provides adequate amounts of vitamin D.

"In a test tube, ultraviolet B is the optimal spectrum for converting 25-hydroxy D into vitamin D in the human body," Dr. Gallo said. "But randomized studies on this vary in results."

One frequently cited study examined the issue in Denmark. "Northern latitudes are very useful for studies like this because of the high intensity of the sun during the summer, and the low intensity in winter," said Dr. Gallo, chief of dermatology and professor of medicine and pediatrics at the University of California San Diego. "In this study, the 25-hydroxy D in the population varied dramatically with change in sunlight exposure, and tended to lag about 1 month behind the sunlight levels."

But the study also found that 53% of the subjects who sought sun exposure were still suboptimal in their vitamin D levels. "So sun-seeking behavior in one of the most intense sun-exposed areas of the world is not sufficient to cover optimal vitamin D in a population." (Photochem. Photobiol. 2009;85:1,480-4).

A 2009 study looked at sunlight exposure and vitamin D in twins (PLoS One 2010 5(7):e11555 [doi: 10.1371/journal.pone.0011555]). More than 200 twins were evaluated for the seasonal impact of genetic factors on serum 25-hydroxy vitamin D concentrations. "This showed very wide distributions in levels during the different seasons, and concluded that more than 50% of the variation in summer levels was not due to sun or diet, but to genetic influences independent of skin pigment," Dr. Gallo said.

"So, Myth No. 1 – busted," he concluded.

Myth No. 2: Vitamin D improves bone health.

Prospective cohort studies such as the National Health and Nutrition Examination Survey show that hip fracture is reduced by more than one-third in patients with adequate vitamin D levels (more than 60 nmol/L). "However, we still have a lot to learn. Data from a recent 3-year study of 2,000 perimenopasual women concluded that if vitamin D were given as a single annual dose of 500,000 IU, the women had a 15% increased risk of falls and a 26% increase in the risk of fractures." (JAMA 2010;303:1815-22).

"As far as Myth No. 2 goes, I'd say it's true, but we don't understand everything yet."

Myth No. 3: Vitamin D protects against cancer.

"This has been quite a popular theme in the press for years now, but there are no great mechanistic explanations as to why it may be true," Dr Gallo said. "There are a number of randomized controlled trials, but the data are inconsistent."

A 2009 Agency for Healthcare Research and Quality review examined more than 170 studies and reviews for several health outcomes and vitamin D. "Only one study really showed a level of significance [for cancer reduction]. The others showed inconsistent data on cancer and some showed a slight trend toward an increased risk for colon cancer." (Evid. Rep. Technol. Assess. (Full Rep.) 2009;183:1-420).

"Myth No. 3 is still a plausible possibility, but no benefit has been clearly demonstrated."

Myth No. 4: Vitamin D improves immune function.

"We have excellent mechanistic data to support this claim, including a number of observational studies and a few randomized controlled trials," Dr. Gallo said.

He coauthored a 2009 study concluding that vitamin D activates an enzyme on the surface of monocytes and keratinocytes, increasing the cells' pattern recognition and boosting their antimicrobial effect. "This enhances the immune barrier in injured skin," Dr. Gallo said (J. Clin. Invest. 2007;117:803-11).

Animal models also "show quite clearly that the extent of infection can be limited in an animal supplemented with vitamin D compared to a deficient one," he added. "There also seems to be a relative association between viral infections and upper respiratory infections, with the highest incidence occurring at the lowest levels of vitamin D on a seasonal basis. So maybe Schlitz did have an idea there. Therefore I’d say Myth No. 4 is plausible, but not yet clearly defined."

Dr. Gallo did not have any relevant financial disclosures. However, he is a member of the Institute of Medicine’s committee on Dietary Reference Intakes for Vitamin D and Calcium. The committee will release new recommendations for national daily requirements of vitamin D and calcium later this year.

CHICAGO – Dr. Richard L. Gallo put on his Myth Busters hat at a recent dermatology meeting to debunk – and in some cases uphold – some of the most popular ideas about vitamin D.

"This subject is nothing new," noted Dr. Gallo, recounting a bit of vitamin D yore. "In 1936, Schlitz beer urged customers to drink the beverage because it contained 100 units of vitamin D, and could ward off colds and flu. So even back then, they were on to something."

But, Dr. Gallo questioned, is the idea that vitamin D can strengthen the immune system a reality – or a myth? And how about other claims touted in the public press, that sunlight is the best source of vitamin D, that the vitamin strengthen bones and protects against cancer.

"Unfortunately, vitamin D information has become something of a shell game, with positions that overstate the strength of the evidence. As dermatologists, for example, we know the carcinogenic potential of sunlight, but there are now opposing groups that advocate health by increasing vitamin D through sun exposure."

Myth No. 1: Fifteen minutes per day of sunlight provides adequate amounts of vitamin D.

"In a test tube, ultraviolet B is the optimal spectrum for converting 25-hydroxy D into vitamin D in the human body," Dr. Gallo said. "But randomized studies on this vary in results."

One frequently cited study examined the issue in Denmark. "Northern latitudes are very useful for studies like this because of the high intensity of the sun during the summer, and the low intensity in winter," said Dr. Gallo, chief of dermatology and professor of medicine and pediatrics at the University of California San Diego. "In this study, the 25-hydroxy D in the population varied dramatically with change in sunlight exposure, and tended to lag about 1 month behind the sunlight levels."

But the study also found that 53% of the subjects who sought sun exposure were still suboptimal in their vitamin D levels. "So sun-seeking behavior in one of the most intense sun-exposed areas of the world is not sufficient to cover optimal vitamin D in a population." (Photochem. Photobiol. 2009;85:1,480-4).

A 2009 study looked at sunlight exposure and vitamin D in twins (PLoS One 2010 5(7):e11555 [doi: 10.1371/journal.pone.0011555]). More than 200 twins were evaluated for the seasonal impact of genetic factors on serum 25-hydroxy vitamin D concentrations. "This showed very wide distributions in levels during the different seasons, and concluded that more than 50% of the variation in summer levels was not due to sun or diet, but to genetic influences independent of skin pigment," Dr. Gallo said.

"So, Myth No. 1 – busted," he concluded.

Myth No. 2: Vitamin D improves bone health.

Prospective cohort studies such as the National Health and Nutrition Examination Survey show that hip fracture is reduced by more than one-third in patients with adequate vitamin D levels (more than 60 nmol/L). "However, we still have a lot to learn. Data from a recent 3-year study of 2,000 perimenopasual women concluded that if vitamin D were given as a single annual dose of 500,000 IU, the women had a 15% increased risk of falls and a 26% increase in the risk of fractures." (JAMA 2010;303:1815-22).

"As far as Myth No. 2 goes, I'd say it's true, but we don't understand everything yet."

Myth No. 3: Vitamin D protects against cancer.

"This has been quite a popular theme in the press for years now, but there are no great mechanistic explanations as to why it may be true," Dr Gallo said. "There are a number of randomized controlled trials, but the data are inconsistent."

A 2009 Agency for Healthcare Research and Quality review examined more than 170 studies and reviews for several health outcomes and vitamin D. "Only one study really showed a level of significance [for cancer reduction]. The others showed inconsistent data on cancer and some showed a slight trend toward an increased risk for colon cancer." (Evid. Rep. Technol. Assess. (Full Rep.) 2009;183:1-420).

"Myth No. 3 is still a plausible possibility, but no benefit has been clearly demonstrated."

Myth No. 4: Vitamin D improves immune function.

"We have excellent mechanistic data to support this claim, including a number of observational studies and a few randomized controlled trials," Dr. Gallo said.

He coauthored a 2009 study concluding that vitamin D activates an enzyme on the surface of monocytes and keratinocytes, increasing the cells' pattern recognition and boosting their antimicrobial effect. "This enhances the immune barrier in injured skin," Dr. Gallo said (J. Clin. Invest. 2007;117:803-11).

Animal models also "show quite clearly that the extent of infection can be limited in an animal supplemented with vitamin D compared to a deficient one," he added. "There also seems to be a relative association between viral infections and upper respiratory infections, with the highest incidence occurring at the lowest levels of vitamin D on a seasonal basis. So maybe Schlitz did have an idea there. Therefore I’d say Myth No. 4 is plausible, but not yet clearly defined."

Dr. Gallo did not have any relevant financial disclosures. However, he is a member of the Institute of Medicine’s committee on Dietary Reference Intakes for Vitamin D and Calcium. The committee will release new recommendations for national daily requirements of vitamin D and calcium later this year.

CHICAGO – Dr. Richard L. Gallo put on his Myth Busters hat at a recent dermatology meeting to debunk – and in some cases uphold – some of the most popular ideas about vitamin D.

"This subject is nothing new," noted Dr. Gallo, recounting a bit of vitamin D yore. "In 1936, Schlitz beer urged customers to drink the beverage because it contained 100 units of vitamin D, and could ward off colds and flu. So even back then, they were on to something."

But, Dr. Gallo questioned, is the idea that vitamin D can strengthen the immune system a reality – or a myth? And how about other claims touted in the public press, that sunlight is the best source of vitamin D, that the vitamin strengthen bones and protects against cancer.

"Unfortunately, vitamin D information has become something of a shell game, with positions that overstate the strength of the evidence. As dermatologists, for example, we know the carcinogenic potential of sunlight, but there are now opposing groups that advocate health by increasing vitamin D through sun exposure."

Myth No. 1: Fifteen minutes per day of sunlight provides adequate amounts of vitamin D.

"In a test tube, ultraviolet B is the optimal spectrum for converting 25-hydroxy D into vitamin D in the human body," Dr. Gallo said. "But randomized studies on this vary in results."

One frequently cited study examined the issue in Denmark. "Northern latitudes are very useful for studies like this because of the high intensity of the sun during the summer, and the low intensity in winter," said Dr. Gallo, chief of dermatology and professor of medicine and pediatrics at the University of California San Diego. "In this study, the 25-hydroxy D in the population varied dramatically with change in sunlight exposure, and tended to lag about 1 month behind the sunlight levels."

But the study also found that 53% of the subjects who sought sun exposure were still suboptimal in their vitamin D levels. "So sun-seeking behavior in one of the most intense sun-exposed areas of the world is not sufficient to cover optimal vitamin D in a population." (Photochem. Photobiol. 2009;85:1,480-4).

A 2009 study looked at sunlight exposure and vitamin D in twins (PLoS One 2010 5(7):e11555 [doi: 10.1371/journal.pone.0011555]). More than 200 twins were evaluated for the seasonal impact of genetic factors on serum 25-hydroxy vitamin D concentrations. "This showed very wide distributions in levels during the different seasons, and concluded that more than 50% of the variation in summer levels was not due to sun or diet, but to genetic influences independent of skin pigment," Dr. Gallo said.

"So, Myth No. 1 – busted," he concluded.

Myth No. 2: Vitamin D improves bone health.

Prospective cohort studies such as the National Health and Nutrition Examination Survey show that hip fracture is reduced by more than one-third in patients with adequate vitamin D levels (more than 60 nmol/L). "However, we still have a lot to learn. Data from a recent 3-year study of 2,000 perimenopasual women concluded that if vitamin D were given as a single annual dose of 500,000 IU, the women had a 15% increased risk of falls and a 26% increase in the risk of fractures." (JAMA 2010;303:1815-22).

"As far as Myth No. 2 goes, I'd say it's true, but we don't understand everything yet."

Myth No. 3: Vitamin D protects against cancer.

"This has been quite a popular theme in the press for years now, but there are no great mechanistic explanations as to why it may be true," Dr Gallo said. "There are a number of randomized controlled trials, but the data are inconsistent."

A 2009 Agency for Healthcare Research and Quality review examined more than 170 studies and reviews for several health outcomes and vitamin D. "Only one study really showed a level of significance [for cancer reduction]. The others showed inconsistent data on cancer and some showed a slight trend toward an increased risk for colon cancer." (Evid. Rep. Technol. Assess. (Full Rep.) 2009;183:1-420).

"Myth No. 3 is still a plausible possibility, but no benefit has been clearly demonstrated."

Myth No. 4: Vitamin D improves immune function.

"We have excellent mechanistic data to support this claim, including a number of observational studies and a few randomized controlled trials," Dr. Gallo said.

He coauthored a 2009 study concluding that vitamin D activates an enzyme on the surface of monocytes and keratinocytes, increasing the cells' pattern recognition and boosting their antimicrobial effect. "This enhances the immune barrier in injured skin," Dr. Gallo said (J. Clin. Invest. 2007;117:803-11).

Animal models also "show quite clearly that the extent of infection can be limited in an animal supplemented with vitamin D compared to a deficient one," he added. "There also seems to be a relative association between viral infections and upper respiratory infections, with the highest incidence occurring at the lowest levels of vitamin D on a seasonal basis. So maybe Schlitz did have an idea there. Therefore I’d say Myth No. 4 is plausible, but not yet clearly defined."

Dr. Gallo did not have any relevant financial disclosures. However, he is a member of the Institute of Medicine’s committee on Dietary Reference Intakes for Vitamin D and Calcium. The committee will release new recommendations for national daily requirements of vitamin D and calcium later this year.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

The first human trial of metformin for precancerous colorectal lesions hints that the diabetes drug may be poised for a second incarnation – this time as a chemopreventive agent for several cancers, including lung, colon, and prostate cancers, and even breast malignancies.

The small study, published in the September issue of Cancer Prevention Research, found that after 1 month of oral metformin, nondiabetic patients who already had at least one colorectal adenoma removed experienced a significant reduction in their number of colorectal aberrant crypt foci – an endoscopic finding that some consider a precursor of adenomatous colon polyps.

A second study, published in the same issue of the journal, found that mice who received the drug after exposure to a potent lung carcinogen developed significantly fewer lung tumors than did those who received a placebo.

In light of these data, physicians may want to look closely at metformin when choosing an oral antidiabetic agent for their patients, Dr. Phillip Dennis of the National Cancer Institute said during a press briefing Sept. 1.

“It’s true that we don’t have an indication for metformin as a cancer chemopreventive,” said Dr. Dennis, lead author of the mouse study. “But a clinician who has four different oral agents for diabetes has to make a choice for his patients, and in that process, this early evidence that metformin may have an oncologic benefit will certainly play a role.”

A growing body of data suggests that metformin reduces the risk of several types of cancer, but thus far the only human evidence had come from observational studies of patients with diabetes. Three epidemiologic studies suggest that metformin decreases the incidence of cancer and cancer-related deaths in diabetic patients by 15%-77% (Euro. J. Cancer 2010;46:2369-2380). In vitro and animal studies suggest similar reductions.

The study released today shows the drug’s potential not only to reduce the number of precancerous lesions, but also to decrease the level of proliferating cell nuclear antigen (PCNA), a marker of tumor virulence, wrote Dr. Kunihiro Hosono of the Yokohama City University School of Medicine, Japan, and colleagues: “This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal aberrant crypt foci, suggesting its promise for the chemoprevention of colorectal cancer” (Cancer Prev. Res. 2010;3:1077-83).

The murine study examined metformin’s potential to prevent lung cancers. Mice that had been exposed to tobacco carcinogens and consumed or were injected with metformin had up to 72% fewer lung tumors than did placebo-treated mice, reported Dr. Dennis and his colleagues (Cancer Prev. Res. 2010;3:1066-76).

Although the new data are exciting, metformin is not ready to grab the spotlight, Dr. Ernest Hawk cautioned in an interview.

“The story is quite compelling, suggesting that metformin may have a role in therapy or in maintenance treatment for cancer survivors,” said Dr. Hawk, division head of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center, Houston. “Before we make any assumptions, though, we need many more trials to figure out if it will live up to the potential it seems to have.”

The Japanese study included 23 nondiabetic patients who had an average of five adenomas removed during a screening colonoscopy. Nine of the patients were treated with 250 mg/day of metformin for 1 month; the remaining 14 did not receive any treatment.

At baseline, the 23 patients had a mean of eight aberrant cryptal foci (ACF). “ACF are tiny lesions that develop in the earliest stage of colorectal carcinogenesis and consist of large, thick crypts,” Dr. Hosono and his team wrote. “ACF have been shown to be precursor lesions of the adenoma-carcinoma sequence in humans, and have been suggested as a suitable surrogate end point for colorectal chemoprevention.”

After the treatment period, patients were examined again; ACF were detected by methylene blue staining of rectal mucosa. The number of lesions decreased significantly in the active group, from a mean of nine per patient to six (P = .007). There was no change in the untreated group (mean of seven at each exam). The mean number of ACF considered dysplastic also decreased significantly in the treated group, while again, there was no change in the untreated group. The drug also proved safe, with no patient experiencing hypoglycemia.

The researchers also examined rectal epithelial proliferation by proliferative cell nuclear antigen (PCNA) immunoassay. The PCNA index decreased significantly in the treated group but remained steady in the untreated group. However, the drug did not affect the percentage of cells undergoing apoptosis.

Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.

“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”

It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”

While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”

A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).

If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).

“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”

Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.

CANCÚN, MEXICO — Feeling the squeeze from government cutbacks and the need to wean itself from big pharma dollars, the Mayo Clinic has found a new source of support for resident education: the Physician Quality Reporting Initiative (PQRI) program.

Launched last year, a program aimed at tracking key measures of diabetes care has helped the Mayo Clinic of Jacksonville, Fla., turn its already strong performance in diabetes care into a revenue stream for the residency program while also improving the consistency of care and giving residents an invaluable window on the logistics of conducting quality improvement projects.

From the outset, however, the goal was on improving diabetes care, Dr. Jerry Sayre emphasized.

The project was spurred by a request from the leaders of Mayo's family medicine department to create a diabetes care improvement program. “In Florida, we spend more than $12 billion each year to care for patients with diabetes,” Dr. Sayre said.

These patients use more health care resources than nondiabetic patients in the clinic's family medicine sector and cost 42% more to care for than nondiabetic patients. Nearly one-quarter of patients hospitalized each year at the Mayo Hospital in Jacksonville have diabetes as a primary diagnosis or comorbidity.

Consistently good preventive care really pays off for this group, Dr. Sayre said. “A hemoglobin A_1c that's decreased by 1% decreases diabetic complications by 35%. And keeping LDL and blood pressure [in normal ranges] decreases cardiovascular morbidity by 50%.”

Using the American Board of Family Medicine's 2010 Diabetes Module, physicians at the clinic identified their most consistently implemented care measures and pinpointed those that needed improvement, he said.

Data collected for the ABFM module can be used to fulfill requirements for the PQRI. Under that program, physicians who meet certain clinical quality standards data for 30 individual Medicare patients can earn an incentive payment of 2% of their total allowed charges for Medicare Physician Fee Schedule–covered professional services.

In the Mayo Clinic's case, that incentive payment amounts to $86,000, which Dr. Sayre plans to funnel back into resident education projects.

In addition to providing an alternative means for fulfilling PQRI requirements, the ABFM's Diabetes Module provides data for generating research and satisfies certification and continuing medical education requirements, said Dr. Sayre.

The module measures how often six clinical tests are performed against what the ABFM considers benchmark rates for patients each year: HbA_1c (benchmark 95%), LDL-cholesterol control (94%), hypertension control (100%), diabetic eye exams (60%), microalbumin testing for diabetic neuropathy (80%), and diabetic foot exams (visual, monofilament, and pulses [77%]). Patient records must contain documentation that each measure was performed in the prior year.

Data were collected on 600 patients seen in Mayo's family medicine clinic during 2009 and were compared with data from a fee-for-service regional medical clinic and national benchmarks.

Mayo physicians were doing “a pretty consistently good job” in most areas, exceeding the benchmark goal for each parameter, Dr. Sayre said. However, “we could have done better in some areas,” such as diabetic foot exams, which were performed 95% of the time. Mayo's goal is to perform it at every visit. As it turned out, a key reason for the shortfall was the lack of monofilaments in every office. “So we purchased monofilaments for each exam room.”

Other measurements included HbA_1c testing documentation (98%), LDL testing (97%), blood pressure control (99%), eye exam (68%), and microalbumin testing (92%).

Scores at the regional medical clinic were almost identical, although two were slightly higher than they were at Mayo: blood pressure control (100%) and eye exams (71%).

Once the data were available, Dr. Sayre and his Mayo Clinic colleagues, Dr. Scott Simmons and Dr. Ramon Cancino, “created a kind of 'doctor report card' to show patients how their doctors are measuring up to these goals,” he explained.

The report shows how each patient's doctor compares with the overall picture of care at the facility and also against national benchmarks.

Dr. Sayre reported having no relevant financial conflicts.

Data from the module can fulfill PQRI incentive requirements; those payments then go back to fund the program.

Source DR. SAYRE

CANCÚN, MEXICO — Feeling the squeeze from government cutbacks and the need to wean itself from big pharma dollars, the Mayo Clinic has found a new source of support for resident education: the Physician Quality Reporting Initiative (PQRI) program.

Launched last year, a program aimed at tracking key measures of diabetes care has helped the Mayo Clinic of Jacksonville, Fla., turn its already strong performance in diabetes care into a revenue stream for the residency program while also improving the consistency of care and giving residents an invaluable window on the logistics of conducting quality improvement projects.

From the outset, however, the goal was on improving diabetes care, Dr. Jerry Sayre emphasized.

The project was spurred by a request from the leaders of Mayo's family medicine department to create a diabetes care improvement program. “In Florida, we spend more than $12 billion each year to care for patients with diabetes,” Dr. Sayre said.

These patients use more health care resources than nondiabetic patients in the clinic's family medicine sector and cost 42% more to care for than nondiabetic patients. Nearly one-quarter of patients hospitalized each year at the Mayo Hospital in Jacksonville have diabetes as a primary diagnosis or comorbidity.

Consistently good preventive care really pays off for this group, Dr. Sayre said. “A hemoglobin A_1c that's decreased by 1% decreases diabetic complications by 35%. And keeping LDL and blood pressure [in normal ranges] decreases cardiovascular morbidity by 50%.”

Using the American Board of Family Medicine's 2010 Diabetes Module, physicians at the clinic identified their most consistently implemented care measures and pinpointed those that needed improvement, he said.

Data collected for the ABFM module can be used to fulfill requirements for the PQRI. Under that program, physicians who meet certain clinical quality standards data for 30 individual Medicare patients can earn an incentive payment of 2% of their total allowed charges for Medicare Physician Fee Schedule–covered professional services.

In the Mayo Clinic's case, that incentive payment amounts to $86,000, which Dr. Sayre plans to funnel back into resident education projects.

In addition to providing an alternative means for fulfilling PQRI requirements, the ABFM's Diabetes Module provides data for generating research and satisfies certification and continuing medical education requirements, said Dr. Sayre.

The module measures how often six clinical tests are performed against what the ABFM considers benchmark rates for patients each year: HbA_1c (benchmark 95%), LDL-cholesterol control (94%), hypertension control (100%), diabetic eye exams (60%), microalbumin testing for diabetic neuropathy (80%), and diabetic foot exams (visual, monofilament, and pulses [77%]). Patient records must contain documentation that each measure was performed in the prior year.

Data were collected on 600 patients seen in Mayo's family medicine clinic during 2009 and were compared with data from a fee-for-service regional medical clinic and national benchmarks.

Mayo physicians were doing “a pretty consistently good job” in most areas, exceeding the benchmark goal for each parameter, Dr. Sayre said. However, “we could have done better in some areas,” such as diabetic foot exams, which were performed 95% of the time. Mayo's goal is to perform it at every visit. As it turned out, a key reason for the shortfall was the lack of monofilaments in every office. “So we purchased monofilaments for each exam room.”

Other measurements included HbA_1c testing documentation (98%), LDL testing (97%), blood pressure control (99%), eye exam (68%), and microalbumin testing (92%).

Scores at the regional medical clinic were almost identical, although two were slightly higher than they were at Mayo: blood pressure control (100%) and eye exams (71%).

Once the data were available, Dr. Sayre and his Mayo Clinic colleagues, Dr. Scott Simmons and Dr. Ramon Cancino, “created a kind of 'doctor report card' to show patients how their doctors are measuring up to these goals,” he explained.

The report shows how each patient's doctor compares with the overall picture of care at the facility and also against national benchmarks.

Dr. Sayre reported having no relevant financial conflicts.

Data from the module can fulfill PQRI incentive requirements; those payments then go back to fund the program.

Source DR. SAYRE

CANCÚN, MEXICO — Feeling the squeeze from government cutbacks and the need to wean itself from big pharma dollars, the Mayo Clinic has found a new source of support for resident education: the Physician Quality Reporting Initiative (PQRI) program.

Launched last year, a program aimed at tracking key measures of diabetes care has helped the Mayo Clinic of Jacksonville, Fla., turn its already strong performance in diabetes care into a revenue stream for the residency program while also improving the consistency of care and giving residents an invaluable window on the logistics of conducting quality improvement projects.

From the outset, however, the goal was on improving diabetes care, Dr. Jerry Sayre emphasized.

The project was spurred by a request from the leaders of Mayo's family medicine department to create a diabetes care improvement program. “In Florida, we spend more than $12 billion each year to care for patients with diabetes,” Dr. Sayre said.

These patients use more health care resources than nondiabetic patients in the clinic's family medicine sector and cost 42% more to care for than nondiabetic patients. Nearly one-quarter of patients hospitalized each year at the Mayo Hospital in Jacksonville have diabetes as a primary diagnosis or comorbidity.

Consistently good preventive care really pays off for this group, Dr. Sayre said. “A hemoglobin A_1c that's decreased by 1% decreases diabetic complications by 35%. And keeping LDL and blood pressure [in normal ranges] decreases cardiovascular morbidity by 50%.”

Using the American Board of Family Medicine's 2010 Diabetes Module, physicians at the clinic identified their most consistently implemented care measures and pinpointed those that needed improvement, he said.

Data collected for the ABFM module can be used to fulfill requirements for the PQRI. Under that program, physicians who meet certain clinical quality standards data for 30 individual Medicare patients can earn an incentive payment of 2% of their total allowed charges for Medicare Physician Fee Schedule–covered professional services.

In the Mayo Clinic's case, that incentive payment amounts to $86,000, which Dr. Sayre plans to funnel back into resident education projects.

In addition to providing an alternative means for fulfilling PQRI requirements, the ABFM's Diabetes Module provides data for generating research and satisfies certification and continuing medical education requirements, said Dr. Sayre.

The module measures how often six clinical tests are performed against what the ABFM considers benchmark rates for patients each year: HbA_1c (benchmark 95%), LDL-cholesterol control (94%), hypertension control (100%), diabetic eye exams (60%), microalbumin testing for diabetic neuropathy (80%), and diabetic foot exams (visual, monofilament, and pulses [77%]). Patient records must contain documentation that each measure was performed in the prior year.

Data were collected on 600 patients seen in Mayo's family medicine clinic during 2009 and were compared with data from a fee-for-service regional medical clinic and national benchmarks.

Mayo physicians were doing “a pretty consistently good job” in most areas, exceeding the benchmark goal for each parameter, Dr. Sayre said. However, “we could have done better in some areas,” such as diabetic foot exams, which were performed 95% of the time. Mayo's goal is to perform it at every visit. As it turned out, a key reason for the shortfall was the lack of monofilaments in every office. “So we purchased monofilaments for each exam room.”

Other measurements included HbA_1c testing documentation (98%), LDL testing (97%), blood pressure control (99%), eye exam (68%), and microalbumin testing (92%).

Scores at the regional medical clinic were almost identical, although two were slightly higher than they were at Mayo: blood pressure control (100%) and eye exams (71%).

Once the data were available, Dr. Sayre and his Mayo Clinic colleagues, Dr. Scott Simmons and Dr. Ramon Cancino, “created a kind of 'doctor report card' to show patients how their doctors are measuring up to these goals,” he explained.

The report shows how each patient's doctor compares with the overall picture of care at the facility and also against national benchmarks.

Dr. Sayre reported having no relevant financial conflicts.

Data from the module can fulfill PQRI incentive requirements; those payments then go back to fund the program.

Source DR. SAYRE

ORLANDO — The adage “Moderation in all things” may directly apply to longevity for people with diabetes, according to a national epidemiologic study from Scotland.

The study of more than 150,000 Scots with type 2 diabetes found that those with extremely high—and extremely low—body mass index were up to twice as likely to die during follow-up as were those with more moderate BMIs.

The study cannot draw any causal links between a moderate BMI and a decrease in mortality, Dr. Jeremy Walker said at the meeting. But it does raise intriguing questions about maintaining a healthy body weight that avoids becoming either over- or underweight.

“Elevated mortality in higher BMI ranges carries urgent and widely recognized public health implications,” said Dr. Walker of the University of Edinburgh Centre for Population Health Sciences. “Elevated BMI is associated with adverse effects on blood pressure, lipid levels, cardiovascular disease risk, glucose metabolism, and cancer.”

While plausible explanations for the relationship between high BMI and death have long existed, explaining the association of low BMI with death is more problematic, Dr. Walker said in an interview. “Low BMI may actually be a consequence of preexisting illness (as is the case in many cancers and much respiratory disease) rather than a cause.”

However, he said, few investigators have drawn attention to the relationship between mortality and the lower range of BMI. One major study, the Prospective Studies Collaboration (PSC), observed a significant relationship between low-normal BMI and all-cause mortality.

The PSC examined the relation between all-cause mortality and baseline BMI in almost 1 million subjects who had been included in 57 prospective studies and followed for a mean of 8 years. The investigators found a very strong U-shaped mortality curve linked with BMI. For both genders, the lowest mortality occurred at 22.5-25 kg/m

Dr. Walker and his coworkers examined the relationship between mortality and BMI in 150,396 patients with type 2 diabetes in the Scottish Care Information Diabetes Collaboration. An initial recording of patients' BMI was linked to national mortality records through 2007, with a mean follow-up of 6 years. The analysis was adjusted for age and socioeconomic status.

There were 81,004 males in the cohort, 13,059 of whom had died by 2007. There were 69,392 females, 11,179 of whom had died by the end of the study.

The mortality and BMI data showed a strong U-shaped curve, with the lowest mortality in the BMI range of 25 to less than 35. For men with a BMI of 15 to less than 20, the risk of death was almost double that of men in the 25-35 range. The risk of death was 1.5 times increased for men with a BMI of 20 to less than 22.5.

Elevation of risk also was observed for men with a BMI of above 35 to 45 kg/m

Women faced similar risks. Women with the lowest BMI of 15 to less than 20 kg/m

The study was sponsored by the Scottish Health Informatics Programme, a collaboration funded by the Wellcome Trust. Dr. Walker had no financial declarations regarding the study.

'Low BMI may actually be a consequence of preexisting illness … rather than a cause' of mortality.

Source DR. WALKER

ORLANDO — The adage “Moderation in all things” may directly apply to longevity for people with diabetes, according to a national epidemiologic study from Scotland.

The study of more than 150,000 Scots with type 2 diabetes found that those with extremely high—and extremely low—body mass index were up to twice as likely to die during follow-up as were those with more moderate BMIs.

The study cannot draw any causal links between a moderate BMI and a decrease in mortality, Dr. Jeremy Walker said at the meeting. But it does raise intriguing questions about maintaining a healthy body weight that avoids becoming either over- or underweight.

“Elevated mortality in higher BMI ranges carries urgent and widely recognized public health implications,” said Dr. Walker of the University of Edinburgh Centre for Population Health Sciences. “Elevated BMI is associated with adverse effects on blood pressure, lipid levels, cardiovascular disease risk, glucose metabolism, and cancer.”

While plausible explanations for the relationship between high BMI and death have long existed, explaining the association of low BMI with death is more problematic, Dr. Walker said in an interview. “Low BMI may actually be a consequence of preexisting illness (as is the case in many cancers and much respiratory disease) rather than a cause.”

However, he said, few investigators have drawn attention to the relationship between mortality and the lower range of BMI. One major study, the Prospective Studies Collaboration (PSC), observed a significant relationship between low-normal BMI and all-cause mortality.

The PSC examined the relation between all-cause mortality and baseline BMI in almost 1 million subjects who had been included in 57 prospective studies and followed for a mean of 8 years. The investigators found a very strong U-shaped mortality curve linked with BMI. For both genders, the lowest mortality occurred at 22.5-25 kg/m

Dr. Walker and his coworkers examined the relationship between mortality and BMI in 150,396 patients with type 2 diabetes in the Scottish Care Information Diabetes Collaboration. An initial recording of patients' BMI was linked to national mortality records through 2007, with a mean follow-up of 6 years. The analysis was adjusted for age and socioeconomic status.

There were 81,004 males in the cohort, 13,059 of whom had died by 2007. There were 69,392 females, 11,179 of whom had died by the end of the study.

The mortality and BMI data showed a strong U-shaped curve, with the lowest mortality in the BMI range of 25 to less than 35. For men with a BMI of 15 to less than 20, the risk of death was almost double that of men in the 25-35 range. The risk of death was 1.5 times increased for men with a BMI of 20 to less than 22.5.

Elevation of risk also was observed for men with a BMI of above 35 to 45 kg/m

Women faced similar risks. Women with the lowest BMI of 15 to less than 20 kg/m

The study was sponsored by the Scottish Health Informatics Programme, a collaboration funded by the Wellcome Trust. Dr. Walker had no financial declarations regarding the study.

'Low BMI may actually be a consequence of preexisting illness … rather than a cause' of mortality.

Source DR. WALKER

ORLANDO — The adage “Moderation in all things” may directly apply to longevity for people with diabetes, according to a national epidemiologic study from Scotland.

The study of more than 150,000 Scots with type 2 diabetes found that those with extremely high—and extremely low—body mass index were up to twice as likely to die during follow-up as were those with more moderate BMIs.

The study cannot draw any causal links between a moderate BMI and a decrease in mortality, Dr. Jeremy Walker said at the meeting. But it does raise intriguing questions about maintaining a healthy body weight that avoids becoming either over- or underweight.

“Elevated mortality in higher BMI ranges carries urgent and widely recognized public health implications,” said Dr. Walker of the University of Edinburgh Centre for Population Health Sciences. “Elevated BMI is associated with adverse effects on blood pressure, lipid levels, cardiovascular disease risk, glucose metabolism, and cancer.”

While plausible explanations for the relationship between high BMI and death have long existed, explaining the association of low BMI with death is more problematic, Dr. Walker said in an interview. “Low BMI may actually be a consequence of preexisting illness (as is the case in many cancers and much respiratory disease) rather than a cause.”

However, he said, few investigators have drawn attention to the relationship between mortality and the lower range of BMI. One major study, the Prospective Studies Collaboration (PSC), observed a significant relationship between low-normal BMI and all-cause mortality.

The PSC examined the relation between all-cause mortality and baseline BMI in almost 1 million subjects who had been included in 57 prospective studies and followed for a mean of 8 years. The investigators found a very strong U-shaped mortality curve linked with BMI. For both genders, the lowest mortality occurred at 22.5-25 kg/m

Dr. Walker and his coworkers examined the relationship between mortality and BMI in 150,396 patients with type 2 diabetes in the Scottish Care Information Diabetes Collaboration. An initial recording of patients' BMI was linked to national mortality records through 2007, with a mean follow-up of 6 years. The analysis was adjusted for age and socioeconomic status.

There were 81,004 males in the cohort, 13,059 of whom had died by 2007. There were 69,392 females, 11,179 of whom had died by the end of the study.

The mortality and BMI data showed a strong U-shaped curve, with the lowest mortality in the BMI range of 25 to less than 35. For men with a BMI of 15 to less than 20, the risk of death was almost double that of men in the 25-35 range. The risk of death was 1.5 times increased for men with a BMI of 20 to less than 22.5.

Elevation of risk also was observed for men with a BMI of above 35 to 45 kg/m

Women faced similar risks. Women with the lowest BMI of 15 to less than 20 kg/m

The study was sponsored by the Scottish Health Informatics Programme, a collaboration funded by the Wellcome Trust. Dr. Walker had no financial declarations regarding the study.

'Low BMI may actually be a consequence of preexisting illness … rather than a cause' of mortality.

Source DR. WALKER

A new guideline issued by the Centers for Disease Control and Prevention aims to help physicians balance the safety and efficacy of different contraceptive methods for all women, whether they are healthy or have an illness that may preclude the use of a specific method.

The Medical Eligibility Criteria for Contraceptive Use 2010 is adapted from a similar evidence-based guideline created by the World Health Organization. The U.S. document, however, includes information on disorders that were not included in the international guideline and updated scientific evidence. It was also formulated to agree with practice guidelines endorsed by U.S. health provider organizations.

A multispecialty board reviewed the WHO document and the extant literature to develop the new guideline. Dr. Robert W. Rebar, the executive director of the American Society for Reproductive Medicine, was a member of the panel. “The [Centers for Disease Control and Prevention] also asked us to recommend some particular diseases that were not covered by the WHO document, but which are relevant in the United States, among them obesity and arthritis,” Dr. Rebar said in an interview.

“Our intent was to provide guidance for physicians as to what kind of contraception appears to be safe and appropriate for these patients,” he said.

The new guideline addresses the use of hormonal contraceptives, emergency contraceptive pills, intrauterine devices for both pregnancy prevention and emergency contraception, barrier methods, sterilization, and “natural methods,” including coitus interruptus, lactational amenorrhea, and fertility awareness. Each method is examined in light of its effect on different groups of patients, and the conditions are ranked according to the related risk (MMWR 2010;59[RR-4]:1-86):

A condition for which there is no restriction for the use of the contraceptive method.

A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

A condition that represents an unacceptable health risk if the contraceptive method is used.

The guideline takes into account not only the safety of each method, but its efficacy as well, Dr. Rebar said. “We attempted to balance the risks of pregnancy—which are not inconsiderable—and the risks of contraception. In each case, physicians can use the guideline to provide patients with an evaluation of the risk, so they can choose” the method that best fits their particular situation and personal needs.

For example, while coitus interruptus is a safe method for any woman, regardless of her physical state, its relative ineffectiveness may not make it a good choice.

“Coitus interruptus is unforgiving of incorrect use, and its effectiveness depends on the willingness and ability of the couple to use withdrawal with every act of intercourse. Women with conditions that make pregnancy an unacceptable risk should be advised that [coitus interruptus] might not be appropriate for them because of its relatively higher typical-use failure rates,” according to the document.

The document also includes a summary of the evidence about potential drug interactions between hormonal contraceptives and antiretroviral therapy. Although there are limited data on the topic, those that do exist suggest that some antiretroviral drugs—particularly the ritonavir-boosted protease inhibitors—can suppress contraceptive steroid blood levels and increase the chance of pregnancy. Other studies suggest that oral contraceptives can increase the likelihood of antiretroviral drug toxicity.

The final pages are devoted to a chart of physical conditions that must be considered when recommending contraceptives, and the possible implications of each method for each reproductive age group. Health care providers can use the summary table as a quick reference guide to the classifications for hormonal contraceptive methods and intrauterine contraception and to compare classifications across these methods.

Disclosures: No conflicts of interest were reported.

The MMWR document is available for free at www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf

A new guideline issued by the Centers for Disease Control and Prevention aims to help physicians balance the safety and efficacy of different contraceptive methods for all women, whether they are healthy or have an illness that may preclude the use of a specific method.

The Medical Eligibility Criteria for Contraceptive Use 2010 is adapted from a similar evidence-based guideline created by the World Health Organization. The U.S. document, however, includes information on disorders that were not included in the international guideline and updated scientific evidence. It was also formulated to agree with practice guidelines endorsed by U.S. health provider organizations.

A multispecialty board reviewed the WHO document and the extant literature to develop the new guideline. Dr. Robert W. Rebar, the executive director of the American Society for Reproductive Medicine, was a member of the panel. “The [Centers for Disease Control and Prevention] also asked us to recommend some particular diseases that were not covered by the WHO document, but which are relevant in the United States, among them obesity and arthritis,” Dr. Rebar said in an interview.

“Our intent was to provide guidance for physicians as to what kind of contraception appears to be safe and appropriate for these patients,” he said.

The new guideline addresses the use of hormonal contraceptives, emergency contraceptive pills, intrauterine devices for both pregnancy prevention and emergency contraception, barrier methods, sterilization, and “natural methods,” including coitus interruptus, lactational amenorrhea, and fertility awareness. Each method is examined in light of its effect on different groups of patients, and the conditions are ranked according to the related risk (MMWR 2010;59[RR-4]:1-86):

A condition for which there is no restriction for the use of the contraceptive method.

A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

A condition that represents an unacceptable health risk if the contraceptive method is used.

The guideline takes into account not only the safety of each method, but its efficacy as well, Dr. Rebar said. “We attempted to balance the risks of pregnancy—which are not inconsiderable—and the risks of contraception. In each case, physicians can use the guideline to provide patients with an evaluation of the risk, so they can choose” the method that best fits their particular situation and personal needs.

For example, while coitus interruptus is a safe method for any woman, regardless of her physical state, its relative ineffectiveness may not make it a good choice.

“Coitus interruptus is unforgiving of incorrect use, and its effectiveness depends on the willingness and ability of the couple to use withdrawal with every act of intercourse. Women with conditions that make pregnancy an unacceptable risk should be advised that [coitus interruptus] might not be appropriate for them because of its relatively higher typical-use failure rates,” according to the document.

The document also includes a summary of the evidence about potential drug interactions between hormonal contraceptives and antiretroviral therapy. Although there are limited data on the topic, those that do exist suggest that some antiretroviral drugs—particularly the ritonavir-boosted protease inhibitors—can suppress contraceptive steroid blood levels and increase the chance of pregnancy. Other studies suggest that oral contraceptives can increase the likelihood of antiretroviral drug toxicity.

The final pages are devoted to a chart of physical conditions that must be considered when recommending contraceptives, and the possible implications of each method for each reproductive age group. Health care providers can use the summary table as a quick reference guide to the classifications for hormonal contraceptive methods and intrauterine contraception and to compare classifications across these methods.

Disclosures: No conflicts of interest were reported.

The MMWR document is available for free at www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf

A new guideline issued by the Centers for Disease Control and Prevention aims to help physicians balance the safety and efficacy of different contraceptive methods for all women, whether they are healthy or have an illness that may preclude the use of a specific method.

The Medical Eligibility Criteria for Contraceptive Use 2010 is adapted from a similar evidence-based guideline created by the World Health Organization. The U.S. document, however, includes information on disorders that were not included in the international guideline and updated scientific evidence. It was also formulated to agree with practice guidelines endorsed by U.S. health provider organizations.

A multispecialty board reviewed the WHO document and the extant literature to develop the new guideline. Dr. Robert W. Rebar, the executive director of the American Society for Reproductive Medicine, was a member of the panel. “The [Centers for Disease Control and Prevention] also asked us to recommend some particular diseases that were not covered by the WHO document, but which are relevant in the United States, among them obesity and arthritis,” Dr. Rebar said in an interview.

“Our intent was to provide guidance for physicians as to what kind of contraception appears to be safe and appropriate for these patients,” he said.

The new guideline addresses the use of hormonal contraceptives, emergency contraceptive pills, intrauterine devices for both pregnancy prevention and emergency contraception, barrier methods, sterilization, and “natural methods,” including coitus interruptus, lactational amenorrhea, and fertility awareness. Each method is examined in light of its effect on different groups of patients, and the conditions are ranked according to the related risk (MMWR 2010;59[RR-4]:1-86):

A condition for which there is no restriction for the use of the contraceptive method.

A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

A condition that represents an unacceptable health risk if the contraceptive method is used.

The guideline takes into account not only the safety of each method, but its efficacy as well, Dr. Rebar said. “We attempted to balance the risks of pregnancy—which are not inconsiderable—and the risks of contraception. In each case, physicians can use the guideline to provide patients with an evaluation of the risk, so they can choose” the method that best fits their particular situation and personal needs.

For example, while coitus interruptus is a safe method for any woman, regardless of her physical state, its relative ineffectiveness may not make it a good choice.

“Coitus interruptus is unforgiving of incorrect use, and its effectiveness depends on the willingness and ability of the couple to use withdrawal with every act of intercourse. Women with conditions that make pregnancy an unacceptable risk should be advised that [coitus interruptus] might not be appropriate for them because of its relatively higher typical-use failure rates,” according to the document.

The document also includes a summary of the evidence about potential drug interactions between hormonal contraceptives and antiretroviral therapy. Although there are limited data on the topic, those that do exist suggest that some antiretroviral drugs—particularly the ritonavir-boosted protease inhibitors—can suppress contraceptive steroid blood levels and increase the chance of pregnancy. Other studies suggest that oral contraceptives can increase the likelihood of antiretroviral drug toxicity.

The final pages are devoted to a chart of physical conditions that must be considered when recommending contraceptives, and the possible implications of each method for each reproductive age group. Health care providers can use the summary table as a quick reference guide to the classifications for hormonal contraceptive methods and intrauterine contraception and to compare classifications across these methods.

Disclosures: No conflicts of interest were reported.

The MMWR document is available for free at www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf