Miriam E. Tucker

PITTSBURGH — Preliminary results from the American Board of Internal Medicine's Comprehensive Care Project confirm what many internists already know intuitively: Overall physician “quality” can't accurately be described using a single or limited number of conditions and/or measures.

“General internists play a central role in caring for patients with multiple medical conditions and comorbidities. However, current physician performance measurement typically focuses on quality measures for a single or a limited number of conditions,” Dr. Eric S. Holmboe said at the annual meeting of the Society of General Internal Medicine.

Results of the ABIM's medical chart audit for 22,526 patients seen by 236 general internists showed wide variation both within and between physicians across a range of medical conditions, suggesting that “assessment of quality using limited numbers of existing performance measures appears not to be an accurate measure of comprehensive physician practice quality,” according to Dr. Holmboe, senior vice president for quality research and academic affairs for the ABIM.

Invitations to participate in the project were mailed to 6,709 general internists with time-limited certification residing in 13 states that were stratified by 2005 state rankings of quality by the Agency for Healthcare Research and Quality (AHRQ). Participants in the performance project received an honorarium and points toward completion of maintenance of certification. Of the 254 physicians who began the project, a total of 236 completed on-site medical record audits.

Medical records were audited for six chronic conditions (diabetes, hypertension, coronary artery disease, heart failure, atrial fibrillation, and osteoarthritis); four acute conditions (upper respiratory infection, urinary tract infection, low back pain, and depression); and six preventive processes of care (smoking cessation counseling, influenza and pneumococcal immunizations, and screening for breast cancer, colon cancer, and osteoporosis). In all, 56 performance measures were abstracted for each physician's practice, said Dr. Holmboe, also of Yale University, New Haven, Conn.

The mean age of the 236 internists was 42 years, and 36% were female. Of the 190 who completed a survey component on practice systems, 36% were in solo practice, 30% in single-specialty practices, 25% in multispecialty practices, and 6% in academic faculty practice.

The medical record audit showed that characteristics of the 22,526 patients varied widely among the physician practices. The mean patient age per physician sample was 60 years, with a per-practice range of 44–77 years. The percentage of women patients averaged 60%, ranging from 10% to 75% per practice. Ethnicity was 37% white, 9% black, 8% Hispanic, and 46% undetermined.

An average of 95 charts was abstracted per physician. Most of the physicians were able to meet the request for at least 20 performance measures each for patients with hypertension (235) and diabetes (215), but fewer could provide the requested 20 for combined upper respiratory infection/urinary tract infection (187) and the three cardiovascular conditions (120), or the 10 charts for low back pain (208). Only about a third of the physicians were able to meet the targets for all six conditions, although half were able to meet the requested targets for at least five, Dr. Holmboe said.

Performance on process and outcome measures for each of the six conditions varied considerably. For example, the two measures with the least successful overall results were foot exams for diabetic patients (11%, range 0%-100%) and appropriate use of nasal decongestants for upper respiratory infections (5%, range 0%-100%). The two measures with the most successful results were weight documentation for heart failure patients (86%, range 0%-100%) and not prescribing drugs for low back pain (86%, range 36%-100%).

For physicians, although there was modest correlation between performance on chronic condition measures and on prevention measures, performance on chronic condition measures correlated poorly with performance on acute condition measures.

Correlation was even lower between performance measures of acute care and prevention.

These preliminary findings suggest that it is feasible to measure quality performance in a general internal medicine practice for some conditions but it may not be possible for all conditions in general internal medicine practices, Dr. Homboe concluded.

PITTSBURGH — Preliminary results from the American Board of Internal Medicine's Comprehensive Care Project confirm what many internists already know intuitively: Overall physician “quality” can't accurately be described using a single or limited number of conditions and/or measures.

“General internists play a central role in caring for patients with multiple medical conditions and comorbidities. However, current physician performance measurement typically focuses on quality measures for a single or a limited number of conditions,” Dr. Eric S. Holmboe said at the annual meeting of the Society of General Internal Medicine.

Results of the ABIM's medical chart audit for 22,526 patients seen by 236 general internists showed wide variation both within and between physicians across a range of medical conditions, suggesting that “assessment of quality using limited numbers of existing performance measures appears not to be an accurate measure of comprehensive physician practice quality,” according to Dr. Holmboe, senior vice president for quality research and academic affairs for the ABIM.

Invitations to participate in the project were mailed to 6,709 general internists with time-limited certification residing in 13 states that were stratified by 2005 state rankings of quality by the Agency for Healthcare Research and Quality (AHRQ). Participants in the performance project received an honorarium and points toward completion of maintenance of certification. Of the 254 physicians who began the project, a total of 236 completed on-site medical record audits.

Medical records were audited for six chronic conditions (diabetes, hypertension, coronary artery disease, heart failure, atrial fibrillation, and osteoarthritis); four acute conditions (upper respiratory infection, urinary tract infection, low back pain, and depression); and six preventive processes of care (smoking cessation counseling, influenza and pneumococcal immunizations, and screening for breast cancer, colon cancer, and osteoporosis). In all, 56 performance measures were abstracted for each physician's practice, said Dr. Holmboe, also of Yale University, New Haven, Conn.

The mean age of the 236 internists was 42 years, and 36% were female. Of the 190 who completed a survey component on practice systems, 36% were in solo practice, 30% in single-specialty practices, 25% in multispecialty practices, and 6% in academic faculty practice.

The medical record audit showed that characteristics of the 22,526 patients varied widely among the physician practices. The mean patient age per physician sample was 60 years, with a per-practice range of 44–77 years. The percentage of women patients averaged 60%, ranging from 10% to 75% per practice. Ethnicity was 37% white, 9% black, 8% Hispanic, and 46% undetermined.

An average of 95 charts was abstracted per physician. Most of the physicians were able to meet the request for at least 20 performance measures each for patients with hypertension (235) and diabetes (215), but fewer could provide the requested 20 for combined upper respiratory infection/urinary tract infection (187) and the three cardiovascular conditions (120), or the 10 charts for low back pain (208). Only about a third of the physicians were able to meet the targets for all six conditions, although half were able to meet the requested targets for at least five, Dr. Holmboe said.

Performance on process and outcome measures for each of the six conditions varied considerably. For example, the two measures with the least successful overall results were foot exams for diabetic patients (11%, range 0%-100%) and appropriate use of nasal decongestants for upper respiratory infections (5%, range 0%-100%). The two measures with the most successful results were weight documentation for heart failure patients (86%, range 0%-100%) and not prescribing drugs for low back pain (86%, range 36%-100%).

For physicians, although there was modest correlation between performance on chronic condition measures and on prevention measures, performance on chronic condition measures correlated poorly with performance on acute condition measures.

Correlation was even lower between performance measures of acute care and prevention.

These preliminary findings suggest that it is feasible to measure quality performance in a general internal medicine practice for some conditions but it may not be possible for all conditions in general internal medicine practices, Dr. Homboe concluded.

PITTSBURGH — Preliminary results from the American Board of Internal Medicine's Comprehensive Care Project confirm what many internists already know intuitively: Overall physician “quality” can't accurately be described using a single or limited number of conditions and/or measures.

“General internists play a central role in caring for patients with multiple medical conditions and comorbidities. However, current physician performance measurement typically focuses on quality measures for a single or a limited number of conditions,” Dr. Eric S. Holmboe said at the annual meeting of the Society of General Internal Medicine.

Results of the ABIM's medical chart audit for 22,526 patients seen by 236 general internists showed wide variation both within and between physicians across a range of medical conditions, suggesting that “assessment of quality using limited numbers of existing performance measures appears not to be an accurate measure of comprehensive physician practice quality,” according to Dr. Holmboe, senior vice president for quality research and academic affairs for the ABIM.

Invitations to participate in the project were mailed to 6,709 general internists with time-limited certification residing in 13 states that were stratified by 2005 state rankings of quality by the Agency for Healthcare Research and Quality (AHRQ). Participants in the performance project received an honorarium and points toward completion of maintenance of certification. Of the 254 physicians who began the project, a total of 236 completed on-site medical record audits.

Medical records were audited for six chronic conditions (diabetes, hypertension, coronary artery disease, heart failure, atrial fibrillation, and osteoarthritis); four acute conditions (upper respiratory infection, urinary tract infection, low back pain, and depression); and six preventive processes of care (smoking cessation counseling, influenza and pneumococcal immunizations, and screening for breast cancer, colon cancer, and osteoporosis). In all, 56 performance measures were abstracted for each physician's practice, said Dr. Holmboe, also of Yale University, New Haven, Conn.

The mean age of the 236 internists was 42 years, and 36% were female. Of the 190 who completed a survey component on practice systems, 36% were in solo practice, 30% in single-specialty practices, 25% in multispecialty practices, and 6% in academic faculty practice.

The medical record audit showed that characteristics of the 22,526 patients varied widely among the physician practices. The mean patient age per physician sample was 60 years, with a per-practice range of 44–77 years. The percentage of women patients averaged 60%, ranging from 10% to 75% per practice. Ethnicity was 37% white, 9% black, 8% Hispanic, and 46% undetermined.

An average of 95 charts was abstracted per physician. Most of the physicians were able to meet the request for at least 20 performance measures each for patients with hypertension (235) and diabetes (215), but fewer could provide the requested 20 for combined upper respiratory infection/urinary tract infection (187) and the three cardiovascular conditions (120), or the 10 charts for low back pain (208). Only about a third of the physicians were able to meet the targets for all six conditions, although half were able to meet the requested targets for at least five, Dr. Holmboe said.

Performance on process and outcome measures for each of the six conditions varied considerably. For example, the two measures with the least successful overall results were foot exams for diabetic patients (11%, range 0%-100%) and appropriate use of nasal decongestants for upper respiratory infections (5%, range 0%-100%). The two measures with the most successful results were weight documentation for heart failure patients (86%, range 0%-100%) and not prescribing drugs for low back pain (86%, range 36%-100%).

For physicians, although there was modest correlation between performance on chronic condition measures and on prevention measures, performance on chronic condition measures correlated poorly with performance on acute condition measures.

Correlation was even lower between performance measures of acute care and prevention.

These preliminary findings suggest that it is feasible to measure quality performance in a general internal medicine practice for some conditions but it may not be possible for all conditions in general internal medicine practices, Dr. Homboe concluded.

SAN FRANCISCO — A novel investigational agent that suppresses resorption of glucose in the kidney improved glycemic control in a 12-week trial of 389 treatment-naive patients with type 2 diabetes.

Bristol-Myers Squibb Co.'s dapagliflozin selectively inhibits the renal sodium-glucose cotransporter 2 (SGLT2), which is the primary transporter of glucose in the kidney, while avoiding the intestinal glucose transporter SGLT1. The inhibition of SGLT2 modulates resorption of glucose in the proximal tubule, which results in excretion of glucose into the urine.

Previous studies have shown that SGLT2 inhibition reduces blood glucose independently of insulin secretion or action and also results in urinary loss of calories, Dr. James F. List said at the annual scientific sessions of the American Diabetes Association.

Dr. List, associate director of global clinical research for Bristol-Myers Squibb Co., Princeton, N.J., presented results from the phase IIb dose-ranging study of dapagliflozin. After a 2-week placebo lead-in phase, the patients were randomized in equal ratios to either once-daily dapagliflozin in doses of 2.5, 5, 10, 20, and 50 mg, metformin (750 mg titrated to 1,500 mg), or placebo for 12 weeks. The 389 patients had a mean age of about 55 years, a mean weight of 89 kg, and a mean body mass index of 31 kg/m

Mean hemoglobin A_1c (HbA_1c) values ranged from 7.7% to 8.0% in all treatment arms and were similar to the median HbA_1c in all groups except the 20-mg arm, which had a median HbA_1c of 7.4%. Mean fasting plasma glucose (FPG) was about 150 mg/dL in all the treatment arms. At baseline, glycosuria levels ranged from 6 g in 24 hours to 11g/24 hours.

Reduction in HbA_1c at 12 weeks, the primary end point, was significant in all dapagliflozin dose groups, ranging from 0.55 percentage points in the 20-mg group to 0.90 in the 50-mg group. Reductions in HbA_1c were 0.71 with 2.5 mg and 0.72 with 5.0 mg, similar to the 0.73 seen with metformin. The placebo group, in contrast, had a reduction of only 0.18. Dose-dependent drops in FPG were similarly significant in all of the dapagliflozin treatment arms, from 16.2 mg/dL in the 2.5-mg treatment group, to 21.1 mg/dL in the 10-mg arm, to 30.5 mg/dL in the group receiving 50 mg dapagliflozin. Reductions in FPG averaged 18.0 mg/dL with metformin and just 5.8 mg/dL with placebo.

Changes in postprandial glucose, assessed by 75-g 3-hour oral glucose tolerance test, also were significant with all doses of dapagliflozin, compared with placebo. However, unlike FPG, those reductions showed no clear dose-dependency, Dr. List said.

The normalized 24-hour urinary glucose:creatinine ratio ranged from 31.72 g/g creatinine at the 2.5-mg dose to 64.75 g/g creatinine for the 20-mg dose, also significant and dose-dependent. There were no changes in those ratios for either metformin or placebo.

The nonnormalized values, expressed as total urinary glucose in 24 hours at week 12, ranged from 51.8 g/day with the lowest dose to a high of 85 g/day with the 20-mg dose (the 50-mg value was similar), compared with baseline values of 5.8–10.9 g/day. That degree of glycosuria translates to a loss of 208–340 calories/day, Dr. List noted.

Changes in weight ranged from 2.5 kg with the 5-mg dapagliflozin dose to 3.4 kg for both the 20-mg and 50-mg doses, compared with 1.7 kg and 1.2 kg with metformin and placebo, respectively. There were no significant changes in serum sodium, potassium, calcium, or urinary calcium, and no changes in renal function assessed by serum creatinine and by measured 24-hour creatinine clearance.

Adverse events were evenly distributed among the study arms, with 63% of the dapagliflozin groups reporting at least one event of any kind, compared with 68% of the metformin patients and 54% with placebo. There were no deaths, and a total of five serious events that were evenly distributed among the dose arms. Discontinuations due to adverse events were also similar between groups, with no particular event standing out, he said.

Hypoglycemia (defined as a confirmed glucose value of 50 mg/dL or below) was not increased in the dapagliflozin groups, in which it ranged from 6%–10%, compared with 9% in the metformin group and 4% with placebo. Rates of urinary tract infections—a concern because of the possibility that the excess urinary glucose could serve as a growth medium for microorganisms—were 5%–12% with dapagliflozin, compared with 9% and 6% for metformin and placebo, respectively.

Genital infections occurred in 2%–3% of the dapagliflozin groups, compared with 2% on metformin and none with placebo. Hypotension—a theoretical concern because of the osmotic diuretic effect of the urinary glucose—was seen in one patient on 50 mg dapagliflozin, two metformin patients, and one on placebo.

Dapagliflozin is now in phase III testing.

SAN FRANCISCO — A novel investigational agent that suppresses resorption of glucose in the kidney improved glycemic control in a 12-week trial of 389 treatment-naive patients with type 2 diabetes.

Bristol-Myers Squibb Co.'s dapagliflozin selectively inhibits the renal sodium-glucose cotransporter 2 (SGLT2), which is the primary transporter of glucose in the kidney, while avoiding the intestinal glucose transporter SGLT1. The inhibition of SGLT2 modulates resorption of glucose in the proximal tubule, which results in excretion of glucose into the urine.

Previous studies have shown that SGLT2 inhibition reduces blood glucose independently of insulin secretion or action and also results in urinary loss of calories, Dr. James F. List said at the annual scientific sessions of the American Diabetes Association.

Dr. List, associate director of global clinical research for Bristol-Myers Squibb Co., Princeton, N.J., presented results from the phase IIb dose-ranging study of dapagliflozin. After a 2-week placebo lead-in phase, the patients were randomized in equal ratios to either once-daily dapagliflozin in doses of 2.5, 5, 10, 20, and 50 mg, metformin (750 mg titrated to 1,500 mg), or placebo for 12 weeks. The 389 patients had a mean age of about 55 years, a mean weight of 89 kg, and a mean body mass index of 31 kg/m

Mean hemoglobin A_1c (HbA_1c) values ranged from 7.7% to 8.0% in all treatment arms and were similar to the median HbA_1c in all groups except the 20-mg arm, which had a median HbA_1c of 7.4%. Mean fasting plasma glucose (FPG) was about 150 mg/dL in all the treatment arms. At baseline, glycosuria levels ranged from 6 g in 24 hours to 11g/24 hours.

Reduction in HbA_1c at 12 weeks, the primary end point, was significant in all dapagliflozin dose groups, ranging from 0.55 percentage points in the 20-mg group to 0.90 in the 50-mg group. Reductions in HbA_1c were 0.71 with 2.5 mg and 0.72 with 5.0 mg, similar to the 0.73 seen with metformin. The placebo group, in contrast, had a reduction of only 0.18. Dose-dependent drops in FPG were similarly significant in all of the dapagliflozin treatment arms, from 16.2 mg/dL in the 2.5-mg treatment group, to 21.1 mg/dL in the 10-mg arm, to 30.5 mg/dL in the group receiving 50 mg dapagliflozin. Reductions in FPG averaged 18.0 mg/dL with metformin and just 5.8 mg/dL with placebo.

Changes in postprandial glucose, assessed by 75-g 3-hour oral glucose tolerance test, also were significant with all doses of dapagliflozin, compared with placebo. However, unlike FPG, those reductions showed no clear dose-dependency, Dr. List said.

The normalized 24-hour urinary glucose:creatinine ratio ranged from 31.72 g/g creatinine at the 2.5-mg dose to 64.75 g/g creatinine for the 20-mg dose, also significant and dose-dependent. There were no changes in those ratios for either metformin or placebo.

The nonnormalized values, expressed as total urinary glucose in 24 hours at week 12, ranged from 51.8 g/day with the lowest dose to a high of 85 g/day with the 20-mg dose (the 50-mg value was similar), compared with baseline values of 5.8–10.9 g/day. That degree of glycosuria translates to a loss of 208–340 calories/day, Dr. List noted.

Changes in weight ranged from 2.5 kg with the 5-mg dapagliflozin dose to 3.4 kg for both the 20-mg and 50-mg doses, compared with 1.7 kg and 1.2 kg with metformin and placebo, respectively. There were no significant changes in serum sodium, potassium, calcium, or urinary calcium, and no changes in renal function assessed by serum creatinine and by measured 24-hour creatinine clearance.

Adverse events were evenly distributed among the study arms, with 63% of the dapagliflozin groups reporting at least one event of any kind, compared with 68% of the metformin patients and 54% with placebo. There were no deaths, and a total of five serious events that were evenly distributed among the dose arms. Discontinuations due to adverse events were also similar between groups, with no particular event standing out, he said.

Hypoglycemia (defined as a confirmed glucose value of 50 mg/dL or below) was not increased in the dapagliflozin groups, in which it ranged from 6%–10%, compared with 9% in the metformin group and 4% with placebo. Rates of urinary tract infections—a concern because of the possibility that the excess urinary glucose could serve as a growth medium for microorganisms—were 5%–12% with dapagliflozin, compared with 9% and 6% for metformin and placebo, respectively.

Genital infections occurred in 2%–3% of the dapagliflozin groups, compared with 2% on metformin and none with placebo. Hypotension—a theoretical concern because of the osmotic diuretic effect of the urinary glucose—was seen in one patient on 50 mg dapagliflozin, two metformin patients, and one on placebo.

Dapagliflozin is now in phase III testing.

SAN FRANCISCO — A novel investigational agent that suppresses resorption of glucose in the kidney improved glycemic control in a 12-week trial of 389 treatment-naive patients with type 2 diabetes.

Bristol-Myers Squibb Co.'s dapagliflozin selectively inhibits the renal sodium-glucose cotransporter 2 (SGLT2), which is the primary transporter of glucose in the kidney, while avoiding the intestinal glucose transporter SGLT1. The inhibition of SGLT2 modulates resorption of glucose in the proximal tubule, which results in excretion of glucose into the urine.

Previous studies have shown that SGLT2 inhibition reduces blood glucose independently of insulin secretion or action and also results in urinary loss of calories, Dr. James F. List said at the annual scientific sessions of the American Diabetes Association.

Dr. List, associate director of global clinical research for Bristol-Myers Squibb Co., Princeton, N.J., presented results from the phase IIb dose-ranging study of dapagliflozin. After a 2-week placebo lead-in phase, the patients were randomized in equal ratios to either once-daily dapagliflozin in doses of 2.5, 5, 10, 20, and 50 mg, metformin (750 mg titrated to 1,500 mg), or placebo for 12 weeks. The 389 patients had a mean age of about 55 years, a mean weight of 89 kg, and a mean body mass index of 31 kg/m

Mean hemoglobin A_1c (HbA_1c) values ranged from 7.7% to 8.0% in all treatment arms and were similar to the median HbA_1c in all groups except the 20-mg arm, which had a median HbA_1c of 7.4%. Mean fasting plasma glucose (FPG) was about 150 mg/dL in all the treatment arms. At baseline, glycosuria levels ranged from 6 g in 24 hours to 11g/24 hours.

Reduction in HbA_1c at 12 weeks, the primary end point, was significant in all dapagliflozin dose groups, ranging from 0.55 percentage points in the 20-mg group to 0.90 in the 50-mg group. Reductions in HbA_1c were 0.71 with 2.5 mg and 0.72 with 5.0 mg, similar to the 0.73 seen with metformin. The placebo group, in contrast, had a reduction of only 0.18. Dose-dependent drops in FPG were similarly significant in all of the dapagliflozin treatment arms, from 16.2 mg/dL in the 2.5-mg treatment group, to 21.1 mg/dL in the 10-mg arm, to 30.5 mg/dL in the group receiving 50 mg dapagliflozin. Reductions in FPG averaged 18.0 mg/dL with metformin and just 5.8 mg/dL with placebo.

Changes in postprandial glucose, assessed by 75-g 3-hour oral glucose tolerance test, also were significant with all doses of dapagliflozin, compared with placebo. However, unlike FPG, those reductions showed no clear dose-dependency, Dr. List said.

The normalized 24-hour urinary glucose:creatinine ratio ranged from 31.72 g/g creatinine at the 2.5-mg dose to 64.75 g/g creatinine for the 20-mg dose, also significant and dose-dependent. There were no changes in those ratios for either metformin or placebo.

The nonnormalized values, expressed as total urinary glucose in 24 hours at week 12, ranged from 51.8 g/day with the lowest dose to a high of 85 g/day with the 20-mg dose (the 50-mg value was similar), compared with baseline values of 5.8–10.9 g/day. That degree of glycosuria translates to a loss of 208–340 calories/day, Dr. List noted.

Changes in weight ranged from 2.5 kg with the 5-mg dapagliflozin dose to 3.4 kg for both the 20-mg and 50-mg doses, compared with 1.7 kg and 1.2 kg with metformin and placebo, respectively. There were no significant changes in serum sodium, potassium, calcium, or urinary calcium, and no changes in renal function assessed by serum creatinine and by measured 24-hour creatinine clearance.

Adverse events were evenly distributed among the study arms, with 63% of the dapagliflozin groups reporting at least one event of any kind, compared with 68% of the metformin patients and 54% with placebo. There were no deaths, and a total of five serious events that were evenly distributed among the dose arms. Discontinuations due to adverse events were also similar between groups, with no particular event standing out, he said.

Hypoglycemia (defined as a confirmed glucose value of 50 mg/dL or below) was not increased in the dapagliflozin groups, in which it ranged from 6%–10%, compared with 9% in the metformin group and 4% with placebo. Rates of urinary tract infections—a concern because of the possibility that the excess urinary glucose could serve as a growth medium for microorganisms—were 5%–12% with dapagliflozin, compared with 9% and 6% for metformin and placebo, respectively.

Genital infections occurred in 2%–3% of the dapagliflozin groups, compared with 2% on metformin and none with placebo. Hypotension—a theoretical concern because of the osmotic diuretic effect of the urinary glucose—was seen in one patient on 50 mg dapagliflozin, two metformin patients, and one on placebo.

Dapagliflozin is now in phase III testing.

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a multinational study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months in 507 individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” lead author Dr. David M. Nathan said at a press briefing during the meeting.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1-6).

Although previous data had provided a rough estimate of average glucose from HbA_1c—and indeed, many labs have long reported those numbers—they were generated from old studies using infrequent fingerstick monitoring. In contrast, the participants in this study, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated approximately 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c - 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

For the overall study results to be considered acceptable, it had been decided a priori that at least 90% of the individual patients' calculated AG would have to fall within 15% of the studywide calculated AG. The actual percentage was 89.95%, and was considered to have met the requirement.

There was no effect of gender, age, ethnicity, diabetes type, or cigarette smoking on the results. However, the number of ethnic minority patients was small, which is a limitation of the study. Other limitations include the lack of data on children, pregnant women, or people with impaired renal function, Dr. Horton noted.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399-400).

At the briefing, study coauthor Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. Now three numbers will be reported, but we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

To anyone who might object to this move, Dr. Nathan reminded the audience that the decision to move to a new standard for HbA_1c measurement and its reporting had come from the IFCC and was not going to change. “We were faced with a change in the units and the reporting that was out of our control. [The IFCC's] new standard is a fine thing, but they were going to report it in a way we thought would be confusing.” Indeed, he noted, a study in Sweden had shown that when laboratories there made a change in units, diabetes control among patients suffered (Diabetes Care 2002;25:2110-1).

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once, and some upgrades could take a year or two. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

When asked whether the HbA_1c percentage value eventually will be eliminated from the physician-patient conversation in favor of the eAG alone, Dr. Nathan replied, “I think that many of us think [eAG] may ultimately replace [HbA_1c]. Why present two numbers when you can present just one?”

Laboratory machines that some physicians have in their offices will be a challenge to upgrade. DR. NATHAN

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a multinational study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months in 507 individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” lead author Dr. David M. Nathan said at a press briefing during the meeting.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1-6).

Although previous data had provided a rough estimate of average glucose from HbA_1c—and indeed, many labs have long reported those numbers—they were generated from old studies using infrequent fingerstick monitoring. In contrast, the participants in this study, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated approximately 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c - 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

For the overall study results to be considered acceptable, it had been decided a priori that at least 90% of the individual patients' calculated AG would have to fall within 15% of the studywide calculated AG. The actual percentage was 89.95%, and was considered to have met the requirement.

There was no effect of gender, age, ethnicity, diabetes type, or cigarette smoking on the results. However, the number of ethnic minority patients was small, which is a limitation of the study. Other limitations include the lack of data on children, pregnant women, or people with impaired renal function, Dr. Horton noted.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399-400).

At the briefing, study coauthor Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. Now three numbers will be reported, but we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

To anyone who might object to this move, Dr. Nathan reminded the audience that the decision to move to a new standard for HbA_1c measurement and its reporting had come from the IFCC and was not going to change. “We were faced with a change in the units and the reporting that was out of our control. [The IFCC's] new standard is a fine thing, but they were going to report it in a way we thought would be confusing.” Indeed, he noted, a study in Sweden had shown that when laboratories there made a change in units, diabetes control among patients suffered (Diabetes Care 2002;25:2110-1).

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once, and some upgrades could take a year or two. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

When asked whether the HbA_1c percentage value eventually will be eliminated from the physician-patient conversation in favor of the eAG alone, Dr. Nathan replied, “I think that many of us think [eAG] may ultimately replace [HbA_1c]. Why present two numbers when you can present just one?”

Laboratory machines that some physicians have in their offices will be a challenge to upgrade. DR. NATHAN

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a multinational study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months in 507 individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” lead author Dr. David M. Nathan said at a press briefing during the meeting.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1-6).

Although previous data had provided a rough estimate of average glucose from HbA_1c—and indeed, many labs have long reported those numbers—they were generated from old studies using infrequent fingerstick monitoring. In contrast, the participants in this study, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated approximately 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c - 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

For the overall study results to be considered acceptable, it had been decided a priori that at least 90% of the individual patients' calculated AG would have to fall within 15% of the studywide calculated AG. The actual percentage was 89.95%, and was considered to have met the requirement.

There was no effect of gender, age, ethnicity, diabetes type, or cigarette smoking on the results. However, the number of ethnic minority patients was small, which is a limitation of the study. Other limitations include the lack of data on children, pregnant women, or people with impaired renal function, Dr. Horton noted.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399-400).

At the briefing, study coauthor Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. Now three numbers will be reported, but we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

To anyone who might object to this move, Dr. Nathan reminded the audience that the decision to move to a new standard for HbA_1c measurement and its reporting had come from the IFCC and was not going to change. “We were faced with a change in the units and the reporting that was out of our control. [The IFCC's] new standard is a fine thing, but they were going to report it in a way we thought would be confusing.” Indeed, he noted, a study in Sweden had shown that when laboratories there made a change in units, diabetes control among patients suffered (Diabetes Care 2002;25:2110-1).

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once, and some upgrades could take a year or two. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

When asked whether the HbA_1c percentage value eventually will be eliminated from the physician-patient conversation in favor of the eAG alone, Dr. Nathan replied, “I think that many of us think [eAG] may ultimately replace [HbA_1c]. Why present two numbers when you can present just one?”

Laboratory machines that some physicians have in their offices will be a challenge to upgrade. DR. NATHAN

SAN FRANCISCO — An investigational once-weekly formulation of exenatide resulted in superior improvements in glucose control at 30 weeks, compared with the current twice-daily version, and elicited sustained glycemic control and weight loss at 1 year in patients with type 2 diabetes.

The phase III data were presented in two separate sessions at the annual scientific sessions of the American Diabetes Association. Known commercially as Byetta, the twice-daily injectable incretin mimetic is comarketed by Amylin Pharmaceuticals Inc., Eli Lilly & Co., and Alkermes Inc. An application for approval of the long-acting release formulation was filed with the Food and Drug Administration in the first quarter of 2008, according to a statement issued by the three companies, which funded the study.

Dr. Daniel J. Drucker, professor of medicine and director of the Banting and Best Diabetes Centre at the University of Toronto, presented the 30-week data from an open-label study in which 295 patients with type 2 diabetes were randomized to receive either the twice-daily formulation (10 mcg twice a day) or the once-weekly version (2 mg/wk). At baseline, about 15% of the patients were drug-naive, while the rest were being treated with one or more oral glucose-lowering agents. They had a mean hemoglobin A_1c (HbA_1c) of 8.3%, fasting plasma glucose (FPG) of 169 mg/dL, body mass index (BMI) of 35 kg/m

Withdrawals prior to 30 weeks were not significantly different between the groups: 13.5% of the 148 patients with the once-weekly formulation, vs. 11.6% of the 147 patients in the twice-daily group. At 30 weeks, the mean HbA_1c had dropped by 1.9 percentage points in the once-weekly group, compared with 1.5% in the twice-daily group. The proportion of patients in the entire cohort achieving an HbA_1c of less than or equal to 7% was 77%, while 49% reached an HbA_1c of 6.5% or below and 25% dropped to 6% or lower. Improvements in HbA_1c were significantly greater among the patients in both formulation groups who had baseline values of 9% or higher, Dr. Drucker reported.

Fasting plasma glucose levels also dropped to a greater degree in the once-weekly group, by 42 mg/dL, compared with 25 mg/dL for the twice-daily patients. Despite the improved glycemic control, weight loss occurred in both groups, with an average loss of 3.6 kg for patients taking the once-weekly formulation and 3.7 kg for patients taking the twice-daily formulation—not significantly different. Reductions in total cholesterol, triglycerides, and systolic and diastolic blood pressure were also seen and were predominantly due to the weight loss, he said.

No major hypoglycemia occurred in either group, and mild hypoglycemia was seen only in the patients taking concurrent sulfonylureas. Injection-site bruising was more common in the twice-daily group than in the once-weekly group (10% vs. 5%). Nausea was less frequent in the once-weekly group (26% vs. 35% for the twice-daily group), but was predominantly mild and transient. And although the patients reporting nausea did lose more weight, those without nausea also experienced weight loss, Dr. Drucker noted.

American Diabetes Association president John Buse presented the 52-week data in a special “Late-Breaking Clinical Studies” session. Following the 30-week study, a total of 120 patients from the once-weekly group continued on that formulation for another 22 weeks, while 121 who had been on the twice-daily version switched to the once-weekly formulation for the next 22 weeks.

Improvements in glycemic control were sustained in the group that stayed on once-weekly exenatide (mean 2.0-percentage point drop from baseline in HbA_1c and FPG reduction of 47 mg/dL), while further improvements from baseline occurred among those who switched to the long-acting formulation (2.0% and 43 mg/dL). The mean HbA_1c in both groups at 52 weeks was 6.6%, said Dr. Buse, professor of medicine, director of the Diabetes Care Center, and chief of the division of endocrinology at the University of North Carolina at Chapel Hill.

Again, the results were far more dramatic among the patients who started with worse glycemic control. Among those with a baseline HbA_1c of 9% or above, the group that took the once-weekly formulation for the entire 52 weeks had dropped by 2.8 percentage points, and those who switched formulations dropped by 2.6. In contrast, those drops were just 1.3% and 1.2%, respectively, among those with baseline HbA_1c levels less than 9%.

Weight loss was similar in both groups at 52 weeks, with the group that stayed on once-weekly exenatide sustaining a 4.1-kg loss from baseline, while those who switched had a mean weight loss of 4.5 kg. Both groups also had clinically significant reductions in both systolic blood pressure (5.7 mm Hg in the once-weekly group and 4.0 mm Hg among those who switched) and diastolic blood pressure (2.2 and 2.1 mm Hg, respectively). Improvements in serum lipid profiles were similar in the two groups at 52 weeks, Dr. Buse said.

Rates of reported nausea were similar at 52 weeks, and lower than they had been at 30 weeks (7.0% for the once-weekly group and 7.7% among those who switched). Injection-site pruritus was reported by 0.8% of the once-weekly group at 52 weeks, compared with 4.6% of the switchers. Again, no severe hypoglycemia occurred and mild hypoglycemia occurred among only the patients also taking sulfonylureas, he reported.

SAN FRANCISCO — An investigational once-weekly formulation of exenatide resulted in superior improvements in glucose control at 30 weeks, compared with the current twice-daily version, and elicited sustained glycemic control and weight loss at 1 year in patients with type 2 diabetes.

The phase III data were presented in two separate sessions at the annual scientific sessions of the American Diabetes Association. Known commercially as Byetta, the twice-daily injectable incretin mimetic is comarketed by Amylin Pharmaceuticals Inc., Eli Lilly & Co., and Alkermes Inc. An application for approval of the long-acting release formulation was filed with the Food and Drug Administration in the first quarter of 2008, according to a statement issued by the three companies, which funded the study.

Dr. Daniel J. Drucker, professor of medicine and director of the Banting and Best Diabetes Centre at the University of Toronto, presented the 30-week data from an open-label study in which 295 patients with type 2 diabetes were randomized to receive either the twice-daily formulation (10 mcg twice a day) or the once-weekly version (2 mg/wk). At baseline, about 15% of the patients were drug-naive, while the rest were being treated with one or more oral glucose-lowering agents. They had a mean hemoglobin A_1c (HbA_1c) of 8.3%, fasting plasma glucose (FPG) of 169 mg/dL, body mass index (BMI) of 35 kg/m

Withdrawals prior to 30 weeks were not significantly different between the groups: 13.5% of the 148 patients with the once-weekly formulation, vs. 11.6% of the 147 patients in the twice-daily group. At 30 weeks, the mean HbA_1c had dropped by 1.9 percentage points in the once-weekly group, compared with 1.5% in the twice-daily group. The proportion of patients in the entire cohort achieving an HbA_1c of less than or equal to 7% was 77%, while 49% reached an HbA_1c of 6.5% or below and 25% dropped to 6% or lower. Improvements in HbA_1c were significantly greater among the patients in both formulation groups who had baseline values of 9% or higher, Dr. Drucker reported.

Fasting plasma glucose levels also dropped to a greater degree in the once-weekly group, by 42 mg/dL, compared with 25 mg/dL for the twice-daily patients. Despite the improved glycemic control, weight loss occurred in both groups, with an average loss of 3.6 kg for patients taking the once-weekly formulation and 3.7 kg for patients taking the twice-daily formulation—not significantly different. Reductions in total cholesterol, triglycerides, and systolic and diastolic blood pressure were also seen and were predominantly due to the weight loss, he said.

No major hypoglycemia occurred in either group, and mild hypoglycemia was seen only in the patients taking concurrent sulfonylureas. Injection-site bruising was more common in the twice-daily group than in the once-weekly group (10% vs. 5%). Nausea was less frequent in the once-weekly group (26% vs. 35% for the twice-daily group), but was predominantly mild and transient. And although the patients reporting nausea did lose more weight, those without nausea also experienced weight loss, Dr. Drucker noted.

American Diabetes Association president John Buse presented the 52-week data in a special “Late-Breaking Clinical Studies” session. Following the 30-week study, a total of 120 patients from the once-weekly group continued on that formulation for another 22 weeks, while 121 who had been on the twice-daily version switched to the once-weekly formulation for the next 22 weeks.

Improvements in glycemic control were sustained in the group that stayed on once-weekly exenatide (mean 2.0-percentage point drop from baseline in HbA_1c and FPG reduction of 47 mg/dL), while further improvements from baseline occurred among those who switched to the long-acting formulation (2.0% and 43 mg/dL). The mean HbA_1c in both groups at 52 weeks was 6.6%, said Dr. Buse, professor of medicine, director of the Diabetes Care Center, and chief of the division of endocrinology at the University of North Carolina at Chapel Hill.

Again, the results were far more dramatic among the patients who started with worse glycemic control. Among those with a baseline HbA_1c of 9% or above, the group that took the once-weekly formulation for the entire 52 weeks had dropped by 2.8 percentage points, and those who switched formulations dropped by 2.6. In contrast, those drops were just 1.3% and 1.2%, respectively, among those with baseline HbA_1c levels less than 9%.

Weight loss was similar in both groups at 52 weeks, with the group that stayed on once-weekly exenatide sustaining a 4.1-kg loss from baseline, while those who switched had a mean weight loss of 4.5 kg. Both groups also had clinically significant reductions in both systolic blood pressure (5.7 mm Hg in the once-weekly group and 4.0 mm Hg among those who switched) and diastolic blood pressure (2.2 and 2.1 mm Hg, respectively). Improvements in serum lipid profiles were similar in the two groups at 52 weeks, Dr. Buse said.

Rates of reported nausea were similar at 52 weeks, and lower than they had been at 30 weeks (7.0% for the once-weekly group and 7.7% among those who switched). Injection-site pruritus was reported by 0.8% of the once-weekly group at 52 weeks, compared with 4.6% of the switchers. Again, no severe hypoglycemia occurred and mild hypoglycemia occurred among only the patients also taking sulfonylureas, he reported.

SAN FRANCISCO — An investigational once-weekly formulation of exenatide resulted in superior improvements in glucose control at 30 weeks, compared with the current twice-daily version, and elicited sustained glycemic control and weight loss at 1 year in patients with type 2 diabetes.

The phase III data were presented in two separate sessions at the annual scientific sessions of the American Diabetes Association. Known commercially as Byetta, the twice-daily injectable incretin mimetic is comarketed by Amylin Pharmaceuticals Inc., Eli Lilly & Co., and Alkermes Inc. An application for approval of the long-acting release formulation was filed with the Food and Drug Administration in the first quarter of 2008, according to a statement issued by the three companies, which funded the study.

Dr. Daniel J. Drucker, professor of medicine and director of the Banting and Best Diabetes Centre at the University of Toronto, presented the 30-week data from an open-label study in which 295 patients with type 2 diabetes were randomized to receive either the twice-daily formulation (10 mcg twice a day) or the once-weekly version (2 mg/wk). At baseline, about 15% of the patients were drug-naive, while the rest were being treated with one or more oral glucose-lowering agents. They had a mean hemoglobin A_1c (HbA_1c) of 8.3%, fasting plasma glucose (FPG) of 169 mg/dL, body mass index (BMI) of 35 kg/m

Withdrawals prior to 30 weeks were not significantly different between the groups: 13.5% of the 148 patients with the once-weekly formulation, vs. 11.6% of the 147 patients in the twice-daily group. At 30 weeks, the mean HbA_1c had dropped by 1.9 percentage points in the once-weekly group, compared with 1.5% in the twice-daily group. The proportion of patients in the entire cohort achieving an HbA_1c of less than or equal to 7% was 77%, while 49% reached an HbA_1c of 6.5% or below and 25% dropped to 6% or lower. Improvements in HbA_1c were significantly greater among the patients in both formulation groups who had baseline values of 9% or higher, Dr. Drucker reported.

Fasting plasma glucose levels also dropped to a greater degree in the once-weekly group, by 42 mg/dL, compared with 25 mg/dL for the twice-daily patients. Despite the improved glycemic control, weight loss occurred in both groups, with an average loss of 3.6 kg for patients taking the once-weekly formulation and 3.7 kg for patients taking the twice-daily formulation—not significantly different. Reductions in total cholesterol, triglycerides, and systolic and diastolic blood pressure were also seen and were predominantly due to the weight loss, he said.

No major hypoglycemia occurred in either group, and mild hypoglycemia was seen only in the patients taking concurrent sulfonylureas. Injection-site bruising was more common in the twice-daily group than in the once-weekly group (10% vs. 5%). Nausea was less frequent in the once-weekly group (26% vs. 35% for the twice-daily group), but was predominantly mild and transient. And although the patients reporting nausea did lose more weight, those without nausea also experienced weight loss, Dr. Drucker noted.

American Diabetes Association president John Buse presented the 52-week data in a special “Late-Breaking Clinical Studies” session. Following the 30-week study, a total of 120 patients from the once-weekly group continued on that formulation for another 22 weeks, while 121 who had been on the twice-daily version switched to the once-weekly formulation for the next 22 weeks.

Improvements in glycemic control were sustained in the group that stayed on once-weekly exenatide (mean 2.0-percentage point drop from baseline in HbA_1c and FPG reduction of 47 mg/dL), while further improvements from baseline occurred among those who switched to the long-acting formulation (2.0% and 43 mg/dL). The mean HbA_1c in both groups at 52 weeks was 6.6%, said Dr. Buse, professor of medicine, director of the Diabetes Care Center, and chief of the division of endocrinology at the University of North Carolina at Chapel Hill.

Again, the results were far more dramatic among the patients who started with worse glycemic control. Among those with a baseline HbA_1c of 9% or above, the group that took the once-weekly formulation for the entire 52 weeks had dropped by 2.8 percentage points, and those who switched formulations dropped by 2.6. In contrast, those drops were just 1.3% and 1.2%, respectively, among those with baseline HbA_1c levels less than 9%.

Weight loss was similar in both groups at 52 weeks, with the group that stayed on once-weekly exenatide sustaining a 4.1-kg loss from baseline, while those who switched had a mean weight loss of 4.5 kg. Both groups also had clinically significant reductions in both systolic blood pressure (5.7 mm Hg in the once-weekly group and 4.0 mm Hg among those who switched) and diastolic blood pressure (2.2 and 2.1 mm Hg, respectively). Improvements in serum lipid profiles were similar in the two groups at 52 weeks, Dr. Buse said.

Rates of reported nausea were similar at 52 weeks, and lower than they had been at 30 weeks (7.0% for the once-weekly group and 7.7% among those who switched). Injection-site pruritus was reported by 0.8% of the once-weekly group at 52 weeks, compared with 4.6% of the switchers. Again, no severe hypoglycemia occurred and mild hypoglycemia occurred among only the patients also taking sulfonylureas, he reported.

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” said lead author Dr. David M. Nathan.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1–6).

The participants, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated about 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable throughout the study, with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c − 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399–400).

Study coauthor, Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. … we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” said lead author Dr. David M. Nathan.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1–6).

The participants, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated about 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable throughout the study, with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c − 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399–400).

Study coauthor, Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. … we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” said lead author Dr. David M. Nathan.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1–6).

The participants, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated about 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable throughout the study, with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c − 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399–400).

Study coauthor, Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. … we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”

The timetable for the new reporting standard is not clear. Manufacturers will need to upgrade laboratory machines with new software, which may not necessarily happen all at once. New point-of-care machines will come with the new standard, but the machines that some physicians already have in their offices will be “more of a challenge” to upgrade, said Dr. Nathan, professor of medicine at Harvard Medical School. In the meantime, the ADA has an online calculator (www.diabetes.org/ag

ARLINGTON, VA. — As hospitals in the United States face the new reality of nonpayment for certain health care-associated infections, ensuring “accurate and appropriate physician documentation on the patient record” is seen by infection control specialists as the area in greatest need of urgent attention.

That finding was among those from a survey of 934 hospital preventionists presented at a conference sponsored by the Association for Professionals in Infection Control and Epidemiology (APIC) and the Premier Healthcare Alliance.

As of Oct. 1, Medicare will no longer pay for care associated with hospital-acquired infections including surgical site infections, catheter-associated urinary tract infections, and vascular catheter-associated infections. Compliance requires documentation of whether the condition was present on admission (POA).

Of the survey respondents, 90% work in infection prevention/control, 2% work in quality/performance improvement, and the rest serve as patient safety experts, as administrators, or in another capacity.

A fourth of the respondents (25%) work in facilities with 100 beds or fewer, 31% work in institutions with 101-250 beds, and 16% work in facilities with 500 or more beds. Most (55%) are located in 1 of the 27 states that currently mandate reporting of health care-acquired infections (HAIs).

Asked which listed activity they believe “needs the most attention to optimize your organization's readiness” for the new payment regulations from the Centers for Medicare and Medicaid Services, 52% responded “accurate/appropriate physician documentation on the patient record.”

Another 20% of the respondents listed “accurate coding, including accurate use of new [POA] codes”; 16% checked “interdepartmental collaboration for identification and documentation of health care-acquired conditions”; and 13% selected “physician education on the impact of the CMS rule” on reimbursement for health care-acquired conditions.

“Everybody's worried about the [POA] issue. They view it as intrusive, something that could potentially create new costs and all sorts of other things,” Dr. Daniel Varga, chief medical officer of St. Louis-based SSM Healthcare, said in an interview.

But “it's probably going to be more of an issue of doctors' needing to be educated, and for us to build processes to make it easy to document presence or absence of [HAIs],” Dr. Varga added.

In a keynote speech, Dr. Thomas B. Valuck, medical officer and senior adviser at CMS, described the new rule as part of the agency's overall “value-based purchasing” strategy. The idea, he said, is to transform Medicare “from a passive player to an active purchaser of higher-quality, more-efficient health care.”

Until now, “Medicare's fee-for-service schedules and prospective payment systems [were] based on resource consumption and quantity of care, not quality or unnecessary costs avoided,” Dr. Valuck noted. If spending continues at the current rate—projected at $486 billion for 2009—the Part A trust fund will be depleted by 2019, he said.

This is the reason for the focus on hospital-acquired infections, which are estimated to add nearly $5 billion annually to the national health care tab. A 2007 study found that, in 2002, 1.7 million hospital-acquired infections were associated with 99,000 deaths. Yet that survey, which was conducted by the employer/insurer coalition known as the Leapfrog Group (www.leapfroggroup.org

The three types of infections designated for nonpayment are among a list of 10 health care-acquired conditions that Medicare no longer covers (and for which CMS has been mandating reporting during the last year). The list includes “never events” such as foreign objects retained after surgery, blood incompatibility, and other conditions such as manifestations of poor glycemic control and injury after a fall (HOSPITALIST NEWS, August 2008, p. 1).

All 10 health care-acquired conditions are subject to the “present on admission” documentation requirement, which defines as POA any conditions present at inpatient admission, including those that arose during outpatient encounters in the emergency department, observation, or outpatient surgery.

There are four possible POA indicators:

Y, which means that the diagnosis was present at the time of admission.

N, which means that the diagnosis wasn't present.

U, which means that documentation was insufficient to determine if the condition was present at the time of admission.

W, which means that the POA status could not be determined despite a full clinical work-up.

Medicare will pay the additional amount for health care-acquired conditions coded as Y or W, but not for those coded as N or U, Dr. Valuck explained.

“The challenge will be to make this a joint effort between the health care provider and the coder,” he said.

The APIC survey also highlighted other challenges that hospitals will face as the new rule goes into effect. Nearly two-thirds (59%) of respondents said that their institution's current surveillance process for detecting problem pathogens and potential HAIs that need investigation was “reasonably timely and efficient” but had “room for improvement,” while 16% said that the process was “not timely and efficient.” Also, 72% said that HAI elimination measures were “moderately” integrated into the tasks of clinicians and other staff; 9% felt that the measures were “very well integrated,” and 17% said the measures were “only indirectly integrated.”

Asked about the biggest challenge for their organization regarding HAI prevention, 36% listed “measuring compliance with infection prevention practices, such as hand hygiene,” and 30% chose “timely and efficient tracking of all or targeted HAIs across the hospital population.”

Among specific HAI prevention interventions, removal of unnecessary indwelling urinary catheters was endorsed by 55% of respondents as being the most challenging in their organizations; smaller proportions listed avoidance of central-line-associated infections (22%), antimicrobial prophylaxis for preventing surgical site infections (16%), and interventions for preventing ventilator-associated infections (6%).

Dr. Varga, who also cochairs the National Quality Forum Steering Committee on Healthcare-Acquired Infections, urged hospital-based physicians to become active participants in the development of protocols for preventing health care-acquired conditions. “Be active in the design and engineering of the protocols, of the process, then be an active participant in the feedback loop that evaluates whether that process is working or not,” he advised.

“A lot of this doesn't directly impact doctors,” Dr. Varga added. “It's the hospital that's not getting paid. But the hospital is going to be all over you to be a participant in this.”

ARLINGTON, VA. — As hospitals in the United States face the new reality of nonpayment for certain health care-associated infections, ensuring “accurate and appropriate physician documentation on the patient record” is seen by infection control specialists as the area in greatest need of urgent attention.

That finding was among those from a survey of 934 hospital preventionists presented at a conference sponsored by the Association for Professionals in Infection Control and Epidemiology (APIC) and the Premier Healthcare Alliance.

As of Oct. 1, Medicare will no longer pay for care associated with hospital-acquired infections including surgical site infections, catheter-associated urinary tract infections, and vascular catheter-associated infections. Compliance requires documentation of whether the condition was present on admission (POA).

Of the survey respondents, 90% work in infection prevention/control, 2% work in quality/performance improvement, and the rest serve as patient safety experts, as administrators, or in another capacity.

A fourth of the respondents (25%) work in facilities with 100 beds or fewer, 31% work in institutions with 101-250 beds, and 16% work in facilities with 500 or more beds. Most (55%) are located in 1 of the 27 states that currently mandate reporting of health care-acquired infections (HAIs).

Asked which listed activity they believe “needs the most attention to optimize your organization's readiness” for the new payment regulations from the Centers for Medicare and Medicaid Services, 52% responded “accurate/appropriate physician documentation on the patient record.”

Another 20% of the respondents listed “accurate coding, including accurate use of new [POA] codes”; 16% checked “interdepartmental collaboration for identification and documentation of health care-acquired conditions”; and 13% selected “physician education on the impact of the CMS rule” on reimbursement for health care-acquired conditions.

“Everybody's worried about the [POA] issue. They view it as intrusive, something that could potentially create new costs and all sorts of other things,” Dr. Daniel Varga, chief medical officer of St. Louis-based SSM Healthcare, said in an interview.

But “it's probably going to be more of an issue of doctors' needing to be educated, and for us to build processes to make it easy to document presence or absence of [HAIs],” Dr. Varga added.

In a keynote speech, Dr. Thomas B. Valuck, medical officer and senior adviser at CMS, described the new rule as part of the agency's overall “value-based purchasing” strategy. The idea, he said, is to transform Medicare “from a passive player to an active purchaser of higher-quality, more-efficient health care.”

Until now, “Medicare's fee-for-service schedules and prospective payment systems [were] based on resource consumption and quantity of care, not quality or unnecessary costs avoided,” Dr. Valuck noted. If spending continues at the current rate—projected at $486 billion for 2009—the Part A trust fund will be depleted by 2019, he said.

This is the reason for the focus on hospital-acquired infections, which are estimated to add nearly $5 billion annually to the national health care tab. A 2007 study found that, in 2002, 1.7 million hospital-acquired infections were associated with 99,000 deaths. Yet that survey, which was conducted by the employer/insurer coalition known as the Leapfrog Group (www.leapfroggroup.org

The three types of infections designated for nonpayment are among a list of 10 health care-acquired conditions that Medicare no longer covers (and for which CMS has been mandating reporting during the last year). The list includes “never events” such as foreign objects retained after surgery, blood incompatibility, and other conditions such as manifestations of poor glycemic control and injury after a fall (HOSPITALIST NEWS, August 2008, p. 1).

All 10 health care-acquired conditions are subject to the “present on admission” documentation requirement, which defines as POA any conditions present at inpatient admission, including those that arose during outpatient encounters in the emergency department, observation, or outpatient surgery.

There are four possible POA indicators:

Y, which means that the diagnosis was present at the time of admission.

N, which means that the diagnosis wasn't present.

U, which means that documentation was insufficient to determine if the condition was present at the time of admission.

W, which means that the POA status could not be determined despite a full clinical work-up.

Medicare will pay the additional amount for health care-acquired conditions coded as Y or W, but not for those coded as N or U, Dr. Valuck explained.

“The challenge will be to make this a joint effort between the health care provider and the coder,” he said.

The APIC survey also highlighted other challenges that hospitals will face as the new rule goes into effect. Nearly two-thirds (59%) of respondents said that their institution's current surveillance process for detecting problem pathogens and potential HAIs that need investigation was “reasonably timely and efficient” but had “room for improvement,” while 16% said that the process was “not timely and efficient.” Also, 72% said that HAI elimination measures were “moderately” integrated into the tasks of clinicians and other staff; 9% felt that the measures were “very well integrated,” and 17% said the measures were “only indirectly integrated.”

Asked about the biggest challenge for their organization regarding HAI prevention, 36% listed “measuring compliance with infection prevention practices, such as hand hygiene,” and 30% chose “timely and efficient tracking of all or targeted HAIs across the hospital population.”

Among specific HAI prevention interventions, removal of unnecessary indwelling urinary catheters was endorsed by 55% of respondents as being the most challenging in their organizations; smaller proportions listed avoidance of central-line-associated infections (22%), antimicrobial prophylaxis for preventing surgical site infections (16%), and interventions for preventing ventilator-associated infections (6%).

Dr. Varga, who also cochairs the National Quality Forum Steering Committee on Healthcare-Acquired Infections, urged hospital-based physicians to become active participants in the development of protocols for preventing health care-acquired conditions. “Be active in the design and engineering of the protocols, of the process, then be an active participant in the feedback loop that evaluates whether that process is working or not,” he advised.

“A lot of this doesn't directly impact doctors,” Dr. Varga added. “It's the hospital that's not getting paid. But the hospital is going to be all over you to be a participant in this.”

ARLINGTON, VA. — As hospitals in the United States face the new reality of nonpayment for certain health care-associated infections, ensuring “accurate and appropriate physician documentation on the patient record” is seen by infection control specialists as the area in greatest need of urgent attention.

That finding was among those from a survey of 934 hospital preventionists presented at a conference sponsored by the Association for Professionals in Infection Control and Epidemiology (APIC) and the Premier Healthcare Alliance.

As of Oct. 1, Medicare will no longer pay for care associated with hospital-acquired infections including surgical site infections, catheter-associated urinary tract infections, and vascular catheter-associated infections. Compliance requires documentation of whether the condition was present on admission (POA).

Of the survey respondents, 90% work in infection prevention/control, 2% work in quality/performance improvement, and the rest serve as patient safety experts, as administrators, or in another capacity.

A fourth of the respondents (25%) work in facilities with 100 beds or fewer, 31% work in institutions with 101-250 beds, and 16% work in facilities with 500 or more beds. Most (55%) are located in 1 of the 27 states that currently mandate reporting of health care-acquired infections (HAIs).

Asked which listed activity they believe “needs the most attention to optimize your organization's readiness” for the new payment regulations from the Centers for Medicare and Medicaid Services, 52% responded “accurate/appropriate physician documentation on the patient record.”

Another 20% of the respondents listed “accurate coding, including accurate use of new [POA] codes”; 16% checked “interdepartmental collaboration for identification and documentation of health care-acquired conditions”; and 13% selected “physician education on the impact of the CMS rule” on reimbursement for health care-acquired conditions.

“Everybody's worried about the [POA] issue. They view it as intrusive, something that could potentially create new costs and all sorts of other things,” Dr. Daniel Varga, chief medical officer of St. Louis-based SSM Healthcare, said in an interview.

But “it's probably going to be more of an issue of doctors' needing to be educated, and for us to build processes to make it easy to document presence or absence of [HAIs],” Dr. Varga added.

In a keynote speech, Dr. Thomas B. Valuck, medical officer and senior adviser at CMS, described the new rule as part of the agency's overall “value-based purchasing” strategy. The idea, he said, is to transform Medicare “from a passive player to an active purchaser of higher-quality, more-efficient health care.”

Until now, “Medicare's fee-for-service schedules and prospective payment systems [were] based on resource consumption and quantity of care, not quality or unnecessary costs avoided,” Dr. Valuck noted. If spending continues at the current rate—projected at $486 billion for 2009—the Part A trust fund will be depleted by 2019, he said.

This is the reason for the focus on hospital-acquired infections, which are estimated to add nearly $5 billion annually to the national health care tab. A 2007 study found that, in 2002, 1.7 million hospital-acquired infections were associated with 99,000 deaths. Yet that survey, which was conducted by the employer/insurer coalition known as the Leapfrog Group (www.leapfroggroup.org

The three types of infections designated for nonpayment are among a list of 10 health care-acquired conditions that Medicare no longer covers (and for which CMS has been mandating reporting during the last year). The list includes “never events” such as foreign objects retained after surgery, blood incompatibility, and other conditions such as manifestations of poor glycemic control and injury after a fall (HOSPITALIST NEWS, August 2008, p. 1).

All 10 health care-acquired conditions are subject to the “present on admission” documentation requirement, which defines as POA any conditions present at inpatient admission, including those that arose during outpatient encounters in the emergency department, observation, or outpatient surgery.

There are four possible POA indicators:

Y, which means that the diagnosis was present at the time of admission.

N, which means that the diagnosis wasn't present.

U, which means that documentation was insufficient to determine if the condition was present at the time of admission.

W, which means that the POA status could not be determined despite a full clinical work-up.

Medicare will pay the additional amount for health care-acquired conditions coded as Y or W, but not for those coded as N or U, Dr. Valuck explained.

“The challenge will be to make this a joint effort between the health care provider and the coder,” he said.

The APIC survey also highlighted other challenges that hospitals will face as the new rule goes into effect. Nearly two-thirds (59%) of respondents said that their institution's current surveillance process for detecting problem pathogens and potential HAIs that need investigation was “reasonably timely and efficient” but had “room for improvement,” while 16% said that the process was “not timely and efficient.” Also, 72% said that HAI elimination measures were “moderately” integrated into the tasks of clinicians and other staff; 9% felt that the measures were “very well integrated,” and 17% said the measures were “only indirectly integrated.”

Asked about the biggest challenge for their organization regarding HAI prevention, 36% listed “measuring compliance with infection prevention practices, such as hand hygiene,” and 30% chose “timely and efficient tracking of all or targeted HAIs across the hospital population.”

Among specific HAI prevention interventions, removal of unnecessary indwelling urinary catheters was endorsed by 55% of respondents as being the most challenging in their organizations; smaller proportions listed avoidance of central-line-associated infections (22%), antimicrobial prophylaxis for preventing surgical site infections (16%), and interventions for preventing ventilator-associated infections (6%).

Dr. Varga, who also cochairs the National Quality Forum Steering Committee on Healthcare-Acquired Infections, urged hospital-based physicians to become active participants in the development of protocols for preventing health care-acquired conditions. “Be active in the design and engineering of the protocols, of the process, then be an active participant in the feedback loop that evaluates whether that process is working or not,” he advised.

“A lot of this doesn't directly impact doctors,” Dr. Varga added. “It's the hospital that's not getting paid. But the hospital is going to be all over you to be a participant in this.”

WASHINGTON — Thrombolytic therapy has resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce amputations, but its use has not extended to the rural northern areas where most cases of frostbite occur.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Prostaglandins and other chemical mediators are released locally, resulting in intense spasm and blistering. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

Traditional treatment has simply been to rewarm the affected extremity, wait to see how much tissue recovers, then amputate the rest, but over the last couple of decades, investigators have been experimenting with intra-arterial infusion of various thrombolytic and vasodilating agents to dissolve clots and relieve arterial spasm in attempts to preserve more tissue.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the process used at Regions Hospital, also in St. Paul. Patients are admitted to the burn unit, where the the affected limb is assessed. Diagnostic arteriography is done to assess small vessel occlusion and loss of "distal tuft blush" at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase, he explained.

During three unusually mild Minnesota winters, six patients aged 18-65 years with severe frostbite who were at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb with coaxial papaverine at 30 mg/hour per limb and intravenous heparin at 500 mcg/hour.

Of the six patients, three who had 16 involved digits responded well and required no amputations. The other three (6 limbs, 30 digits) had incomplete angiographic responses. Of those, two (4 limbs, 20 involved digits) improved following TNK infusion but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved.

Those patients were compared with surviving patients (aged 14-77 years) of 12 treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, four had lost 31 digits at 45 days, and two had amputations but more distally than would have been anticipated without treatment.

Fingers with severe frostbite (left) can be saved from amputation with restored blood flow (right) after treatment with tenecteplase, papaverine, and heparin. Photos courtesy Dr. George R. Edmonson

WASHINGTON — Thrombolytic therapy has resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce amputations, but its use has not extended to the rural northern areas where most cases of frostbite occur.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Prostaglandins and other chemical mediators are released locally, resulting in intense spasm and blistering. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

Traditional treatment has simply been to rewarm the affected extremity, wait to see how much tissue recovers, then amputate the rest, but over the last couple of decades, investigators have been experimenting with intra-arterial infusion of various thrombolytic and vasodilating agents to dissolve clots and relieve arterial spasm in attempts to preserve more tissue.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the process used at Regions Hospital, also in St. Paul. Patients are admitted to the burn unit, where the the affected limb is assessed. Diagnostic arteriography is done to assess small vessel occlusion and loss of "distal tuft blush" at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase, he explained.

During three unusually mild Minnesota winters, six patients aged 18-65 years with severe frostbite who were at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb with coaxial papaverine at 30 mg/hour per limb and intravenous heparin at 500 mcg/hour.

Of the six patients, three who had 16 involved digits responded well and required no amputations. The other three (6 limbs, 30 digits) had incomplete angiographic responses. Of those, two (4 limbs, 20 involved digits) improved following TNK infusion but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved.

Those patients were compared with surviving patients (aged 14-77 years) of 12 treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, four had lost 31 digits at 45 days, and two had amputations but more distally than would have been anticipated without treatment.

Fingers with severe frostbite (left) can be saved from amputation with restored blood flow (right) after treatment with tenecteplase, papaverine, and heparin. Photos courtesy Dr. George R. Edmonson

WASHINGTON — Thrombolytic therapy has resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce amputations, but its use has not extended to the rural northern areas where most cases of frostbite occur.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Prostaglandins and other chemical mediators are released locally, resulting in intense spasm and blistering. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

Traditional treatment has simply been to rewarm the affected extremity, wait to see how much tissue recovers, then amputate the rest, but over the last couple of decades, investigators have been experimenting with intra-arterial infusion of various thrombolytic and vasodilating agents to dissolve clots and relieve arterial spasm in attempts to preserve more tissue.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the process used at Regions Hospital, also in St. Paul. Patients are admitted to the burn unit, where the the affected limb is assessed. Diagnostic arteriography is done to assess small vessel occlusion and loss of "distal tuft blush" at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase, he explained.

During three unusually mild Minnesota winters, six patients aged 18-65 years with severe frostbite who were at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb with coaxial papaverine at 30 mg/hour per limb and intravenous heparin at 500 mcg/hour.

Of the six patients, three who had 16 involved digits responded well and required no amputations. The other three (6 limbs, 30 digits) had incomplete angiographic responses. Of those, two (4 limbs, 20 involved digits) improved following TNK infusion but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved.

Those patients were compared with surviving patients (aged 14-77 years) of 12 treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, four had lost 31 digits at 45 days, and two had amputations but more distally than would have been anticipated without treatment.

Fingers with severe frostbite (left) can be saved from amputation with restored blood flow (right) after treatment with tenecteplase, papaverine, and heparin. Photos courtesy Dr. George R. Edmonson

ORLANDO — A deficiency of vitamin D is extremely common among patients with diabetes and other endocrine conditions, according to findings from two recent studies.

In one study, Dr. Kanakasabai Nara- simhan and Dr. Ali A. Rizvi of the University of South Carolina, Columbia, looked at 97 patients who were seen at their institution's diabetes unit. The group comprised 39 men and 58 women, with an average age of 55 years. Two-thirds of the patients were white and one-third were black. The researchers presented their findings in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

The mean serum calcium for the study group was 9.46 mg/dL (reference range, 8.6–10.2), mean serum creatinine was 1.06 mg/dL (range, 0.5–1.3), average hemoglobin A_1c (HbA_1c) was 7.52%, and most of the patients had estimated glomerular filtration rate values greater than 60 mL/min per 1.73 m

The average serum 25-hydroxyvitamin D (25[OH]D) level for the group was 23.3 ng/mL (range, 7–68 ng/mL). “Deficient” or “extremely low” 25(OH)D values less than or equal to 20 ng/mL were found in 49 patients (50.5%), whereas 23 patients (23.7%) had “relatively insufficient” levels in the 21- to 29-ng/mL range. Only 25 patients (25.8%) had 25(OH)D levels of 30 ng/mL or greater, which is considered “sufficient” or normal, Dr. Narasimhan and Dr. Rizvi reported.

The mean 25(OH)D values were slightly lower in women (22.6 ng/mL) than in men (24.4 ng/mL). Younger patients tended to have lower mean 25(OH)D values, with 22.9 ng/mL among those younger than 50 years, 25.8 ng/ml in those aged 50–59 years, and 23.5 ng/mL among those aged 60 years and older. The mean 25(OH)D value was also slightly lower among those with poorer diabetes control (22.54 ng/mL for the patients with HbA_1c levels above 7%, compared with 24.3 ng/mL for those who had HbA_1c levels of 7% or lower).

Although none of these correlations was statistically significant, the findings may still be clinically important in a selected population such as this one. Alternatively, “the lack of a clear-cut association with any single parameter may be due to the general risk that the presence of diabetes imparts, or may simply reflect the high prevalence of vitamin D deficiency in the general population,” Dr. Narasimhan and Dr. Rizvi said.

Regardless, until the data are confirmed, “consideration may be given to recommendations for screening for vitamin D deficiency in the diabetic population,” they concluded.

In the other study, which was also presented in a poster at the meeting, Dr. Syeda Zaidi and Dr. Thomas A. Hughes of the University of Tennessee, Memphis, reviewed the charts of 262 patients seen over a 6-year period at a private endocrinology-lipid clinic. The “relatively healthy, affluent” group had a mean age of 59.9 years (range, 21–88 years); 89% were white, 7% were black, and 46% were male. Their mean serum calcium level was 9.6 mg/dL (range, 7.8–11.0 mg/dL) and serum creatinine was 1.0 mg/dL (range, 0.5–2.0 mg/dL). One-fourth had known osteopenia or osteoporosis. Other diagnoses included hyperlipidemia (92%), type 2 diabetes (60%), and thyroid disease (28%).

Severe 25(OH)D deficiency (below 10 ng/mL) was present in 6% of the patients, moderate deficiency (10–20 ng/mL) in 32%, and mild deficiency (20–32 ng/mL) in 35%. Only 11% had levels considered satisfactory (above 40 ng/mL). These patients were typically younger and/or on low-dose vitamin D supplements. However, 23% of the patients with 25(OH)D levels below 32 ng/mL were taking low-dose vitamin D supplements, and 58% were taking multivitamin supplements.

Moreover, only one of the 18 black patients in the group had 25(OH)D levels above 32 ng/mL, noted Dr. Zaidi and Dr. Hughes. They also pointed out that their institution is located in the Sunbelt, where one might expect to see higher 25(OH)D levels than elsewhere in the country.

“Vitamin D deficiency and secondary hyperparathyroidism are associated with metabolic bone disease, myopathy, cardiomyopathy, vasculopathy, and carcinogenesis. Therefore, this high incidence of deficit could have widespread clinical consequences,” they commented.

ORLANDO — A deficiency of vitamin D is extremely common among patients with diabetes and other endocrine conditions, according to findings from two recent studies.

In one study, Dr. Kanakasabai Nara- simhan and Dr. Ali A. Rizvi of the University of South Carolina, Columbia, looked at 97 patients who were seen at their institution's diabetes unit. The group comprised 39 men and 58 women, with an average age of 55 years. Two-thirds of the patients were white and one-third were black. The researchers presented their findings in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

The mean serum calcium for the study group was 9.46 mg/dL (reference range, 8.6–10.2), mean serum creatinine was 1.06 mg/dL (range, 0.5–1.3), average hemoglobin A_1c (HbA_1c) was 7.52%, and most of the patients had estimated glomerular filtration rate values greater than 60 mL/min per 1.73 m

The average serum 25-hydroxyvitamin D (25[OH]D) level for the group was 23.3 ng/mL (range, 7–68 ng/mL). “Deficient” or “extremely low” 25(OH)D values less than or equal to 20 ng/mL were found in 49 patients (50.5%), whereas 23 patients (23.7%) had “relatively insufficient” levels in the 21- to 29-ng/mL range. Only 25 patients (25.8%) had 25(OH)D levels of 30 ng/mL or greater, which is considered “sufficient” or normal, Dr. Narasimhan and Dr. Rizvi reported.

The mean 25(OH)D values were slightly lower in women (22.6 ng/mL) than in men (24.4 ng/mL). Younger patients tended to have lower mean 25(OH)D values, with 22.9 ng/mL among those younger than 50 years, 25.8 ng/ml in those aged 50–59 years, and 23.5 ng/mL among those aged 60 years and older. The mean 25(OH)D value was also slightly lower among those with poorer diabetes control (22.54 ng/mL for the patients with HbA_1c levels above 7%, compared with 24.3 ng/mL for those who had HbA_1c levels of 7% or lower).

Although none of these correlations was statistically significant, the findings may still be clinically important in a selected population such as this one. Alternatively, “the lack of a clear-cut association with any single parameter may be due to the general risk that the presence of diabetes imparts, or may simply reflect the high prevalence of vitamin D deficiency in the general population,” Dr. Narasimhan and Dr. Rizvi said.

Regardless, until the data are confirmed, “consideration may be given to recommendations for screening for vitamin D deficiency in the diabetic population,” they concluded.

In the other study, which was also presented in a poster at the meeting, Dr. Syeda Zaidi and Dr. Thomas A. Hughes of the University of Tennessee, Memphis, reviewed the charts of 262 patients seen over a 6-year period at a private endocrinology-lipid clinic. The “relatively healthy, affluent” group had a mean age of 59.9 years (range, 21–88 years); 89% were white, 7% were black, and 46% were male. Their mean serum calcium level was 9.6 mg/dL (range, 7.8–11.0 mg/dL) and serum creatinine was 1.0 mg/dL (range, 0.5–2.0 mg/dL). One-fourth had known osteopenia or osteoporosis. Other diagnoses included hyperlipidemia (92%), type 2 diabetes (60%), and thyroid disease (28%).

Severe 25(OH)D deficiency (below 10 ng/mL) was present in 6% of the patients, moderate deficiency (10–20 ng/mL) in 32%, and mild deficiency (20–32 ng/mL) in 35%. Only 11% had levels considered satisfactory (above 40 ng/mL). These patients were typically younger and/or on low-dose vitamin D supplements. However, 23% of the patients with 25(OH)D levels below 32 ng/mL were taking low-dose vitamin D supplements, and 58% were taking multivitamin supplements.

Moreover, only one of the 18 black patients in the group had 25(OH)D levels above 32 ng/mL, noted Dr. Zaidi and Dr. Hughes. They also pointed out that their institution is located in the Sunbelt, where one might expect to see higher 25(OH)D levels than elsewhere in the country.

“Vitamin D deficiency and secondary hyperparathyroidism are associated with metabolic bone disease, myopathy, cardiomyopathy, vasculopathy, and carcinogenesis. Therefore, this high incidence of deficit could have widespread clinical consequences,” they commented.

ORLANDO — A deficiency of vitamin D is extremely common among patients with diabetes and other endocrine conditions, according to findings from two recent studies.

In one study, Dr. Kanakasabai Nara- simhan and Dr. Ali A. Rizvi of the University of South Carolina, Columbia, looked at 97 patients who were seen at their institution's diabetes unit. The group comprised 39 men and 58 women, with an average age of 55 years. Two-thirds of the patients were white and one-third were black. The researchers presented their findings in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

The mean serum calcium for the study group was 9.46 mg/dL (reference range, 8.6–10.2), mean serum creatinine was 1.06 mg/dL (range, 0.5–1.3), average hemoglobin A_1c (HbA_1c) was 7.52%, and most of the patients had estimated glomerular filtration rate values greater than 60 mL/min per 1.73 m

The average serum 25-hydroxyvitamin D (25[OH]D) level for the group was 23.3 ng/mL (range, 7–68 ng/mL). “Deficient” or “extremely low” 25(OH)D values less than or equal to 20 ng/mL were found in 49 patients (50.5%), whereas 23 patients (23.7%) had “relatively insufficient” levels in the 21- to 29-ng/mL range. Only 25 patients (25.8%) had 25(OH)D levels of 30 ng/mL or greater, which is considered “sufficient” or normal, Dr. Narasimhan and Dr. Rizvi reported.

The mean 25(OH)D values were slightly lower in women (22.6 ng/mL) than in men (24.4 ng/mL). Younger patients tended to have lower mean 25(OH)D values, with 22.9 ng/mL among those younger than 50 years, 25.8 ng/ml in those aged 50–59 years, and 23.5 ng/mL among those aged 60 years and older. The mean 25(OH)D value was also slightly lower among those with poorer diabetes control (22.54 ng/mL for the patients with HbA_1c levels above 7%, compared with 24.3 ng/mL for those who had HbA_1c levels of 7% or lower).

Although none of these correlations was statistically significant, the findings may still be clinically important in a selected population such as this one. Alternatively, “the lack of a clear-cut association with any single parameter may be due to the general risk that the presence of diabetes imparts, or may simply reflect the high prevalence of vitamin D deficiency in the general population,” Dr. Narasimhan and Dr. Rizvi said.

Regardless, until the data are confirmed, “consideration may be given to recommendations for screening for vitamin D deficiency in the diabetic population,” they concluded.

In the other study, which was also presented in a poster at the meeting, Dr. Syeda Zaidi and Dr. Thomas A. Hughes of the University of Tennessee, Memphis, reviewed the charts of 262 patients seen over a 6-year period at a private endocrinology-lipid clinic. The “relatively healthy, affluent” group had a mean age of 59.9 years (range, 21–88 years); 89% were white, 7% were black, and 46% were male. Their mean serum calcium level was 9.6 mg/dL (range, 7.8–11.0 mg/dL) and serum creatinine was 1.0 mg/dL (range, 0.5–2.0 mg/dL). One-fourth had known osteopenia or osteoporosis. Other diagnoses included hyperlipidemia (92%), type 2 diabetes (60%), and thyroid disease (28%).

Severe 25(OH)D deficiency (below 10 ng/mL) was present in 6% of the patients, moderate deficiency (10–20 ng/mL) in 32%, and mild deficiency (20–32 ng/mL) in 35%. Only 11% had levels considered satisfactory (above 40 ng/mL). These patients were typically younger and/or on low-dose vitamin D supplements. However, 23% of the patients with 25(OH)D levels below 32 ng/mL were taking low-dose vitamin D supplements, and 58% were taking multivitamin supplements.

Moreover, only one of the 18 black patients in the group had 25(OH)D levels above 32 ng/mL, noted Dr. Zaidi and Dr. Hughes. They also pointed out that their institution is located in the Sunbelt, where one might expect to see higher 25(OH)D levels than elsewhere in the country.

“Vitamin D deficiency and secondary hyperparathyroidism are associated with metabolic bone disease, myopathy, cardiomyopathy, vasculopathy, and carcinogenesis. Therefore, this high incidence of deficit could have widespread clinical consequences,” they commented.

WASHINGTON — Isolated pharmaco-mechanical thrombolysis using the Trellis-8 peripheral infusion system achieved at least 50% thrombus removal with restored patency in over 90% of 827 limbs in 771 patients with deep vein thrombosis.

That finding was among the prospective data collected from Trellis manufacturer Bacchus Vascular's patient registry presented by Dr. Gerard J. O'Sullivan at the annual meeting of the Society of Interventional Radiology.

Intended as an adjunct to anticoagulation, pharmaco-mechanical thrombectomy combines physical maceration of the clot and drug dispersal through the clot, followed by aspiration of the clot out of the body. In contrast to catheter-directed thrombolysis (CDT), which takes 2–3 days, usually requires a stay in intensive care, and incurs a 10%–20% risk of bleeding complications, pharmaco-mechanical thrombectomy can be done in a single setting in less than 2 hours with far less chance of bleeding, said Dr. O'Sullivan, an interventional radiologist with University Hospital, Galway, Ireland.

The data set included 827 venous limbs in 771 patients, with procedures performed between February 2005 and February 2008 at 362 centers in the United States, Canada, Ireland, and Belgium. Mean patient age was 54 years, with 51% female.

Clinical presentation of the clot—based on the Society of Interventional Radiology's reporting criteria (J. Vasc. Interv. Radiol. 2006;17:417–34)—was acute (present for 14 days or less) in 74% (608) of the limbs, including 44% (360) in patients who also had venographic evidence of a previous deep vein thrombosis (DVT) that had been present for longer than 28 days (defined as chronic). Another 10% (87) had subacute DVT (15–28 days), 11% (89) had “subacute on chronic,” and 5% (43) had chronic DVT alone. The majority (85%) of clots were in a lower extremity. Of those 703, 79% (554) had iliac involvement. Among the upper extremity clots, most (90%) were subclavian only.

Outcomes were slightly better for acute than for chronic clots: Lysis of either grade II (50%–94% thrombus removal) or grade III (95% or greater thrombus removal) was achieved in 97% of the acute-only clots, in 94% of the “acute on chronic” clots, 95% of the subacute clots, 89% of the “subacute on chronic,” and in 91% of the chronic-only clots. Venous patency was established in all cases, Dr. O'Sullivan said.

Adjunctive therapies delivered during the primary procedure included percutaneous transluminal angioplasty (PTA) alone in 46%, stent alone in 4%, and PTA plus stent in 27%. In most of these cases, the reason for the adjunctive treatment was either underlying chronic obstruction or culprit lesion that would have greatly increased the likelihood of DVT recurrence if not treated, he explained.

More than 80% of all cases—ranging from 77% of the subacute and acute/chronic clots to 95% of the chronic—were completed in a single setting in less than 2 hours, with an average Trellis-8 use time of 22 minutes. Tissue plasminogen activator was the thrombolytic used in most (93%) of the cases, at an average lytic dose of 6.0 mg per run, 13.4 mg total per patient. These doses are considerably lower than those used with CDT, he noted.

No bleeding complications were reported in short-term follow-up.

The percutaneous Trellis-8 peripheral infusion system, designed specifically for single-setting DVT thrombolysis, comprises an 8 French catheter with two occluding balloons and drug infusion holes between the balloons. With the clot isolated between the two balloons within a targeted vessel, the device mechanically disperses infused thrombolytic agents directly to it with a rotational motion (video is available at www.bacchusvascular.com

All data for this study were obtained from the data registry maintained by the device manufacturer, Bacchus Vascular.

WASHINGTON — Isolated pharmaco-mechanical thrombolysis using the Trellis-8 peripheral infusion system achieved at least 50% thrombus removal with restored patency in over 90% of 827 limbs in 771 patients with deep vein thrombosis.

That finding was among the prospective data collected from Trellis manufacturer Bacchus Vascular's patient registry presented by Dr. Gerard J. O'Sullivan at the annual meeting of the Society of Interventional Radiology.

Intended as an adjunct to anticoagulation, pharmaco-mechanical thrombectomy combines physical maceration of the clot and drug dispersal through the clot, followed by aspiration of the clot out of the body. In contrast to catheter-directed thrombolysis (CDT), which takes 2–3 days, usually requires a stay in intensive care, and incurs a 10%–20% risk of bleeding complications, pharmaco-mechanical thrombectomy can be done in a single setting in less than 2 hours with far less chance of bleeding, said Dr. O'Sullivan, an interventional radiologist with University Hospital, Galway, Ireland.

The data set included 827 venous limbs in 771 patients, with procedures performed between February 2005 and February 2008 at 362 centers in the United States, Canada, Ireland, and Belgium. Mean patient age was 54 years, with 51% female.

Clinical presentation of the clot—based on the Society of Interventional Radiology's reporting criteria (J. Vasc. Interv. Radiol. 2006;17:417–34)—was acute (present for 14 days or less) in 74% (608) of the limbs, including 44% (360) in patients who also had venographic evidence of a previous deep vein thrombosis (DVT) that had been present for longer than 28 days (defined as chronic). Another 10% (87) had subacute DVT (15–28 days), 11% (89) had “subacute on chronic,” and 5% (43) had chronic DVT alone. The majority (85%) of clots were in a lower extremity. Of those 703, 79% (554) had iliac involvement. Among the upper extremity clots, most (90%) were subclavian only.

Outcomes were slightly better for acute than for chronic clots: Lysis of either grade II (50%–94% thrombus removal) or grade III (95% or greater thrombus removal) was achieved in 97% of the acute-only clots, in 94% of the “acute on chronic” clots, 95% of the subacute clots, 89% of the “subacute on chronic,” and in 91% of the chronic-only clots. Venous patency was established in all cases, Dr. O'Sullivan said.

Adjunctive therapies delivered during the primary procedure included percutaneous transluminal angioplasty (PTA) alone in 46%, stent alone in 4%, and PTA plus stent in 27%. In most of these cases, the reason for the adjunctive treatment was either underlying chronic obstruction or culprit lesion that would have greatly increased the likelihood of DVT recurrence if not treated, he explained.

More than 80% of all cases—ranging from 77% of the subacute and acute/chronic clots to 95% of the chronic—were completed in a single setting in less than 2 hours, with an average Trellis-8 use time of 22 minutes. Tissue plasminogen activator was the thrombolytic used in most (93%) of the cases, at an average lytic dose of 6.0 mg per run, 13.4 mg total per patient. These doses are considerably lower than those used with CDT, he noted.

No bleeding complications were reported in short-term follow-up.

The percutaneous Trellis-8 peripheral infusion system, designed specifically for single-setting DVT thrombolysis, comprises an 8 French catheter with two occluding balloons and drug infusion holes between the balloons. With the clot isolated between the two balloons within a targeted vessel, the device mechanically disperses infused thrombolytic agents directly to it with a rotational motion (video is available at www.bacchusvascular.com

All data for this study were obtained from the data registry maintained by the device manufacturer, Bacchus Vascular.

WASHINGTON — Isolated pharmaco-mechanical thrombolysis using the Trellis-8 peripheral infusion system achieved at least 50% thrombus removal with restored patency in over 90% of 827 limbs in 771 patients with deep vein thrombosis.

That finding was among the prospective data collected from Trellis manufacturer Bacchus Vascular's patient registry presented by Dr. Gerard J. O'Sullivan at the annual meeting of the Society of Interventional Radiology.

Intended as an adjunct to anticoagulation, pharmaco-mechanical thrombectomy combines physical maceration of the clot and drug dispersal through the clot, followed by aspiration of the clot out of the body. In contrast to catheter-directed thrombolysis (CDT), which takes 2–3 days, usually requires a stay in intensive care, and incurs a 10%–20% risk of bleeding complications, pharmaco-mechanical thrombectomy can be done in a single setting in less than 2 hours with far less chance of bleeding, said Dr. O'Sullivan, an interventional radiologist with University Hospital, Galway, Ireland.

The data set included 827 venous limbs in 771 patients, with procedures performed between February 2005 and February 2008 at 362 centers in the United States, Canada, Ireland, and Belgium. Mean patient age was 54 years, with 51% female.

Clinical presentation of the clot—based on the Society of Interventional Radiology's reporting criteria (J. Vasc. Interv. Radiol. 2006;17:417–34)—was acute (present for 14 days or less) in 74% (608) of the limbs, including 44% (360) in patients who also had venographic evidence of a previous deep vein thrombosis (DVT) that had been present for longer than 28 days (defined as chronic). Another 10% (87) had subacute DVT (15–28 days), 11% (89) had “subacute on chronic,” and 5% (43) had chronic DVT alone. The majority (85%) of clots were in a lower extremity. Of those 703, 79% (554) had iliac involvement. Among the upper extremity clots, most (90%) were subclavian only.

Outcomes were slightly better for acute than for chronic clots: Lysis of either grade II (50%–94% thrombus removal) or grade III (95% or greater thrombus removal) was achieved in 97% of the acute-only clots, in 94% of the “acute on chronic” clots, 95% of the subacute clots, 89% of the “subacute on chronic,” and in 91% of the chronic-only clots. Venous patency was established in all cases, Dr. O'Sullivan said.

Adjunctive therapies delivered during the primary procedure included percutaneous transluminal angioplasty (PTA) alone in 46%, stent alone in 4%, and PTA plus stent in 27%. In most of these cases, the reason for the adjunctive treatment was either underlying chronic obstruction or culprit lesion that would have greatly increased the likelihood of DVT recurrence if not treated, he explained.

More than 80% of all cases—ranging from 77% of the subacute and acute/chronic clots to 95% of the chronic—were completed in a single setting in less than 2 hours, with an average Trellis-8 use time of 22 minutes. Tissue plasminogen activator was the thrombolytic used in most (93%) of the cases, at an average lytic dose of 6.0 mg per run, 13.4 mg total per patient. These doses are considerably lower than those used with CDT, he noted.

No bleeding complications were reported in short-term follow-up.

The percutaneous Trellis-8 peripheral infusion system, designed specifically for single-setting DVT thrombolysis, comprises an 8 French catheter with two occluding balloons and drug infusion holes between the balloons. With the clot isolated between the two balloons within a targeted vessel, the device mechanically disperses infused thrombolytic agents directly to it with a rotational motion (video is available at www.bacchusvascular.com

All data for this study were obtained from the data registry maintained by the device manufacturer, Bacchus Vascular.

Infusion pump technology for treating diabetes and pain management might pose special risks for adolescent patients, a 10-year Food and Drug Administration analysis of 1,647 medical device adverse event reports in patients aged 12–21 years suggests.

Prompted by five adolescent death reports associated with the use of insulin pumps during 2005, the agency conducted a search of its own medical device adverse events reports database for all those related to either insulin pumps or patient-controlled analgesia (PCA) pumps for adolescents from Jan. 1, 1996, through Dec. 31, 2005. Included are 1,594 reports for insulin pumps and 53 for PCA pumps, with 13 deaths in the former and 5 for the latter.

“[Adolescents] deserve careful consideration of risk and benefit for use of device technology. Studies need to further identify safety problems in this age group,” said Dr. Judith U. Cope of the FDA's Division of Postmarket Surveillance and her associates (Pediatrics 2008;121:e1133–8).

However, pediatric endocrinologist Dr. Francine R. Kaufman sees the insulin pump part of the article as “an example of reporting bias” because no equivalent data are included about insulin injection regimens or the risks of diabetes itself in adolescents.

“There is evidence in the pediatric community of reduction in hypoglycemia, improvement in [hemoglobin] A1c, improvement in quality of life measures with pump use. Insulin pump therapy allows for a better outcome for those children appropriately selected and willing and able to manage diabetes,” Dr. Kaufman, professor of pediatrics at the University of Southern California and director of the Comprehensive Childhood Diabetes Center and head of the Center for Endocrinology, Diabetes, and Metabolism at Childrens Hospital Los Angeles, said in an interview.

The number of insulin pump adverse event reports to the FDA for adolescents increased annually over the 10-year period. There were 1,038 injuries, 528 device malfunctions, 13 deaths, and 15 events classified as “other.”

Since 2003, a greater proportion of the reports were for patient injuries than for device malfunctions. Of the 499 reports in 2005, 76% were patient injuries and 22% were device malfunctions. Deaths made up 1%, and the remaining reports were classified as other.

Of the 13 insulin pump-related deaths over the period, 5 were related to either hyperglycemic or hypoglycemic complications, 3 to diabetic ketoacidosis, 1 to seizure, and 1 to coma; 3 death reports did not indicate a cause.

Of the total, 987 (62%) reported episodes of hyperglycemia, 47% indicated the patient had diabetic ketoacidosis. Of the 987 hyperglycemia reports, 7% concerned underinfusion. There were some reports of the device's need for repair, replacement, or removal, and also of device failure and/or failure to deliver.

Another 167 (10.5%) reports involved patient and device problems with hypoglycemia or overdelivery of insulin. A small number of reports were coded as incorrect use of the device, problem with self-activating key and overbolusing, error message, and alarm problems. The problem was coded as unknown for 60 of the 167 reports.

Special adolescent issues were identified in 6% (102) of the reports, including 82 resulting in hospitalization. The top three of these involved education, noncompliance, and problems during sports or other activities. Four of the reports indicated risk-taking behaviors, including two cases of insulin overbolusing that were believed to be suicide attempts. Three deaths occurred when there was no parental supervision.

“An increased risk for hypoglycemic complications may occur with binge drinking of alcohol,” the investigators said.

Most of the 53 PCA pump-related events occurred in patients using the devices to treat pain associated with orthopedic conditions, cancer, sickle cell disease, and pregnancy-related events; there were 19 injuries, 21 device malfunctions, and 8 other events.

In 51% of the reports, the patient received an excess dose of medication, and in 12 of those 27 reports the patient had respiratory depression and unresponsiveness requiring ventilation and/or Narcan administration. Two patients tampered with the pump and removed morphine from the device, and one smoked marijuana while using the pump.

To report device-related problems, visit www.fda.gov/medwatch

Insulin pump therapy allows for a better outcome in appropriately selected children who are able to manage diabetes. DR. KAUFMAN

Infusion pump technology for treating diabetes and pain management might pose special risks for adolescent patients, a 10-year Food and Drug Administration analysis of 1,647 medical device adverse event reports in patients aged 12–21 years suggests.

Prompted by five adolescent death reports associated with the use of insulin pumps during 2005, the agency conducted a search of its own medical device adverse events reports database for all those related to either insulin pumps or patient-controlled analgesia (PCA) pumps for adolescents from Jan. 1, 1996, through Dec. 31, 2005. Included are 1,594 reports for insulin pumps and 53 for PCA pumps, with 13 deaths in the former and 5 for the latter.

“[Adolescents] deserve careful consideration of risk and benefit for use of device technology. Studies need to further identify safety problems in this age group,” said Dr. Judith U. Cope of the FDA's Division of Postmarket Surveillance and her associates (Pediatrics 2008;121:e1133–8).

However, pediatric endocrinologist Dr. Francine R. Kaufman sees the insulin pump part of the article as “an example of reporting bias” because no equivalent data are included about insulin injection regimens or the risks of diabetes itself in adolescents.

“There is evidence in the pediatric community of reduction in hypoglycemia, improvement in [hemoglobin] A1c, improvement in quality of life measures with pump use. Insulin pump therapy allows for a better outcome for those children appropriately selected and willing and able to manage diabetes,” Dr. Kaufman, professor of pediatrics at the University of Southern California and director of the Comprehensive Childhood Diabetes Center and head of the Center for Endocrinology, Diabetes, and Metabolism at Childrens Hospital Los Angeles, said in an interview.

The number of insulin pump adverse event reports to the FDA for adolescents increased annually over the 10-year period. There were 1,038 injuries, 528 device malfunctions, 13 deaths, and 15 events classified as “other.”

Since 2003, a greater proportion of the reports were for patient injuries than for device malfunctions. Of the 499 reports in 2005, 76% were patient injuries and 22% were device malfunctions. Deaths made up 1%, and the remaining reports were classified as other.

Of the 13 insulin pump-related deaths over the period, 5 were related to either hyperglycemic or hypoglycemic complications, 3 to diabetic ketoacidosis, 1 to seizure, and 1 to coma; 3 death reports did not indicate a cause.

Of the total, 987 (62%) reported episodes of hyperglycemia, 47% indicated the patient had diabetic ketoacidosis. Of the 987 hyperglycemia reports, 7% concerned underinfusion. There were some reports of the device's need for repair, replacement, or removal, and also of device failure and/or failure to deliver.

Another 167 (10.5%) reports involved patient and device problems with hypoglycemia or overdelivery of insulin. A small number of reports were coded as incorrect use of the device, problem with self-activating key and overbolusing, error message, and alarm problems. The problem was coded as unknown for 60 of the 167 reports.

Special adolescent issues were identified in 6% (102) of the reports, including 82 resulting in hospitalization. The top three of these involved education, noncompliance, and problems during sports or other activities. Four of the reports indicated risk-taking behaviors, including two cases of insulin overbolusing that were believed to be suicide attempts. Three deaths occurred when there was no parental supervision.

“An increased risk for hypoglycemic complications may occur with binge drinking of alcohol,” the investigators said.

Most of the 53 PCA pump-related events occurred in patients using the devices to treat pain associated with orthopedic conditions, cancer, sickle cell disease, and pregnancy-related events; there were 19 injuries, 21 device malfunctions, and 8 other events.

In 51% of the reports, the patient received an excess dose of medication, and in 12 of those 27 reports the patient had respiratory depression and unresponsiveness requiring ventilation and/or Narcan administration. Two patients tampered with the pump and removed morphine from the device, and one smoked marijuana while using the pump.

To report device-related problems, visit www.fda.gov/medwatch

Insulin pump therapy allows for a better outcome in appropriately selected children who are able to manage diabetes. DR. KAUFMAN

Infusion pump technology for treating diabetes and pain management might pose special risks for adolescent patients, a 10-year Food and Drug Administration analysis of 1,647 medical device adverse event reports in patients aged 12–21 years suggests.

Prompted by five adolescent death reports associated with the use of insulin pumps during 2005, the agency conducted a search of its own medical device adverse events reports database for all those related to either insulin pumps or patient-controlled analgesia (PCA) pumps for adolescents from Jan. 1, 1996, through Dec. 31, 2005. Included are 1,594 reports for insulin pumps and 53 for PCA pumps, with 13 deaths in the former and 5 for the latter.

“[Adolescents] deserve careful consideration of risk and benefit for use of device technology. Studies need to further identify safety problems in this age group,” said Dr. Judith U. Cope of the FDA's Division of Postmarket Surveillance and her associates (Pediatrics 2008;121:e1133–8).

However, pediatric endocrinologist Dr. Francine R. Kaufman sees the insulin pump part of the article as “an example of reporting bias” because no equivalent data are included about insulin injection regimens or the risks of diabetes itself in adolescents.

“There is evidence in the pediatric community of reduction in hypoglycemia, improvement in [hemoglobin] A1c, improvement in quality of life measures with pump use. Insulin pump therapy allows for a better outcome for those children appropriately selected and willing and able to manage diabetes,” Dr. Kaufman, professor of pediatrics at the University of Southern California and director of the Comprehensive Childhood Diabetes Center and head of the Center for Endocrinology, Diabetes, and Metabolism at Childrens Hospital Los Angeles, said in an interview.

The number of insulin pump adverse event reports to the FDA for adolescents increased annually over the 10-year period. There were 1,038 injuries, 528 device malfunctions, 13 deaths, and 15 events classified as “other.”

Since 2003, a greater proportion of the reports were for patient injuries than for device malfunctions. Of the 499 reports in 2005, 76% were patient injuries and 22% were device malfunctions. Deaths made up 1%, and the remaining reports were classified as other.

Of the 13 insulin pump-related deaths over the period, 5 were related to either hyperglycemic or hypoglycemic complications, 3 to diabetic ketoacidosis, 1 to seizure, and 1 to coma; 3 death reports did not indicate a cause.

Of the total, 987 (62%) reported episodes of hyperglycemia, 47% indicated the patient had diabetic ketoacidosis. Of the 987 hyperglycemia reports, 7% concerned underinfusion. There were some reports of the device's need for repair, replacement, or removal, and also of device failure and/or failure to deliver.

Another 167 (10.5%) reports involved patient and device problems with hypoglycemia or overdelivery of insulin. A small number of reports were coded as incorrect use of the device, problem with self-activating key and overbolusing, error message, and alarm problems. The problem was coded as unknown for 60 of the 167 reports.

Special adolescent issues were identified in 6% (102) of the reports, including 82 resulting in hospitalization. The top three of these involved education, noncompliance, and problems during sports or other activities. Four of the reports indicated risk-taking behaviors, including two cases of insulin overbolusing that were believed to be suicide attempts. Three deaths occurred when there was no parental supervision.

“An increased risk for hypoglycemic complications may occur with binge drinking of alcohol,” the investigators said.

Most of the 53 PCA pump-related events occurred in patients using the devices to treat pain associated with orthopedic conditions, cancer, sickle cell disease, and pregnancy-related events; there were 19 injuries, 21 device malfunctions, and 8 other events.

In 51% of the reports, the patient received an excess dose of medication, and in 12 of those 27 reports the patient had respiratory depression and unresponsiveness requiring ventilation and/or Narcan administration. Two patients tampered with the pump and removed morphine from the device, and one smoked marijuana while using the pump.

To report device-related problems, visit www.fda.gov/medwatch

Insulin pump therapy allows for a better outcome in appropriately selected children who are able to manage diabetes. DR. KAUFMAN