Miriam E. Tucker

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy. Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, who is professor of epidemiology at the University of Pittsburgh.

Follow-up data were examined for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and for participants in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977–86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994. The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years. The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

Based on data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%). For nephropathy (defined as having albuminuria greater than 300 mg/24 hour or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively. Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially. The improvements seen in the recent cohorts may underestimate the improvements currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” Dr. Orchard noted.

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy. Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, who is professor of epidemiology at the University of Pittsburgh.

Follow-up data were examined for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and for participants in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977–86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994. The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years. The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

Based on data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%). For nephropathy (defined as having albuminuria greater than 300 mg/24 hour or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively. Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially. The improvements seen in the recent cohorts may underestimate the improvements currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” Dr. Orchard noted.

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy. Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, who is professor of epidemiology at the University of Pittsburgh.

Follow-up data were examined for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and for participants in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977–86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994. The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years. The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

Based on data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%). For nephropathy (defined as having albuminuria greater than 300 mg/24 hour or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively. Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially. The improvements seen in the recent cohorts may underestimate the improvements currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” Dr. Orchard noted.

ROME — Youth with type 2 diabetes had an average of nearly three cardiovascular risk factors each, compared with just one among healthy controls in an analysis of 295 participants in a large, multicenter, U.S. case-control study.

The data come from 106 patients with type 2 diabetes and 189 healthy controls (matched for age, sex, and race/ethnicity) recruited by primary care providers at two sites (Colorado and South Carolina) of the six sites participating in the federally-funded SEARCH for Diabetes in Youth, a study designed to investigate the prevalence and characteristics of diabetes among individuals aged younger than 20 years (www.searchfordiabetes.org

The current analysis, one of the first to look specifically at cardiovascular (CV) risk in youth with type 2 diabetes, also revealed that not all of the risk factors could be accounted for by increased obesity and/or hyperglycemia. “We believe that our data support the statement that early prevention and treatment strategies aimed at reducing the prevalence of cardiovascular risk factors in youth with type 2 diabetes mellitus are urgently needed,” Dr. Dana Dabelea said at the annual meeting of the European Association for the Study of Diabetes.

Participants were aged 10–22 years, with a mean of 16 years for the diabetic group and 14 years for the controls. (This was a statistically significant difference, despite attempts to age-match.) Duration of diabetes in the type 2 group was 1.5 years. Females comprised 69% of the diabetic group and 60% of controls, not significantly different, said Dr. Dabelea, director of the epidemiology PhD program at the University of Colorado, Denver, and a principal investigator at the SEARCH Colorado site.

The type 2 group was significantly more likely than were the controls to be African American (55% vs. 29%) and less likely to be non-Hispanic white (28% vs. 54%). The proportion of Hispanics was 17% in both groups. Body mass index was significantly greater among the youth with diabetes (35 vs. 24 kg/m

Consumption of saturated fat as a percent of total daily calories was slightly higher in the type 2 group, while the amount of daily physical activity was lower, but these did not reach statistical significance.

Highly statistically significant differences were seen between the two groups in the proportions—adjusted for age and race/ethnicity—who had hypertension, defined as systolic or diastolic blood pressure of 95th percentile or greater for age, sex, height, or medication (27% in the type 2 group vs. 5% of controls), low HDL cholesterol, defined as 35 mg/dL or below (25% of the type 2 group vs. 5% of controls) and high triglycerides, of 150 mg/dL or higher (27% vs. 6%).

Also highly significantly different were the proportions who were obese, defined as 95th percentile or greater BMI for age and sex (86% vs. 26%) and those who had a large waist circumference, defined as 90th percentile or greater for age and sex (82% vs. 22%).

Elevated albumin/creatinine ratio of 30 mcg/mg or greater was present in 17% of the type 2 group vs. 7% of controls, of borderline significance. The proportions of patients with high LDL cholesterol (130 mg/dL or greater) and who were current smokers were not significantly different, she said.

Nearly half (45%) of the controls had none of these CV risk factors, compared with just 3% of those with type 2 diabetes. In contrast, 60% of the type 2 patients had three or more risk factors, compared with just 13% of the nondiabetic controls. Those with type 2 diabetes had a mean of 2.9 CV risk factors each, compared with 1 for the controls.

The type 2 group also had a less favorable profile of nontraditional CV risk factors, including significantly lower levels of adiponectin and LDL particle density, and higher levels of apolipoprotein B, fibrinogen, and interleukin-6.

In a series of multiple linear regression models, adjustment for differences in obesity accounted for the differences between the type 2 group and the controls in HDL cholesterol, systolic blood pressure, and adiponectin, while adjustment for hemoglobin A_1c between the groups accounted for the differences in apolipoprotein B and LDL particle size. Adjustment for both obesity and HbA_1c accounted for the difference in triglycerides.

ROME — Youth with type 2 diabetes had an average of nearly three cardiovascular risk factors each, compared with just one among healthy controls in an analysis of 295 participants in a large, multicenter, U.S. case-control study.

The data come from 106 patients with type 2 diabetes and 189 healthy controls (matched for age, sex, and race/ethnicity) recruited by primary care providers at two sites (Colorado and South Carolina) of the six sites participating in the federally-funded SEARCH for Diabetes in Youth, a study designed to investigate the prevalence and characteristics of diabetes among individuals aged younger than 20 years (www.searchfordiabetes.org

The current analysis, one of the first to look specifically at cardiovascular (CV) risk in youth with type 2 diabetes, also revealed that not all of the risk factors could be accounted for by increased obesity and/or hyperglycemia. “We believe that our data support the statement that early prevention and treatment strategies aimed at reducing the prevalence of cardiovascular risk factors in youth with type 2 diabetes mellitus are urgently needed,” Dr. Dana Dabelea said at the annual meeting of the European Association for the Study of Diabetes.

Participants were aged 10–22 years, with a mean of 16 years for the diabetic group and 14 years for the controls. (This was a statistically significant difference, despite attempts to age-match.) Duration of diabetes in the type 2 group was 1.5 years. Females comprised 69% of the diabetic group and 60% of controls, not significantly different, said Dr. Dabelea, director of the epidemiology PhD program at the University of Colorado, Denver, and a principal investigator at the SEARCH Colorado site.

The type 2 group was significantly more likely than were the controls to be African American (55% vs. 29%) and less likely to be non-Hispanic white (28% vs. 54%). The proportion of Hispanics was 17% in both groups. Body mass index was significantly greater among the youth with diabetes (35 vs. 24 kg/m

Consumption of saturated fat as a percent of total daily calories was slightly higher in the type 2 group, while the amount of daily physical activity was lower, but these did not reach statistical significance.

Highly statistically significant differences were seen between the two groups in the proportions—adjusted for age and race/ethnicity—who had hypertension, defined as systolic or diastolic blood pressure of 95th percentile or greater for age, sex, height, or medication (27% in the type 2 group vs. 5% of controls), low HDL cholesterol, defined as 35 mg/dL or below (25% of the type 2 group vs. 5% of controls) and high triglycerides, of 150 mg/dL or higher (27% vs. 6%).

Also highly significantly different were the proportions who were obese, defined as 95th percentile or greater BMI for age and sex (86% vs. 26%) and those who had a large waist circumference, defined as 90th percentile or greater for age and sex (82% vs. 22%).

Elevated albumin/creatinine ratio of 30 mcg/mg or greater was present in 17% of the type 2 group vs. 7% of controls, of borderline significance. The proportions of patients with high LDL cholesterol (130 mg/dL or greater) and who were current smokers were not significantly different, she said.

Nearly half (45%) of the controls had none of these CV risk factors, compared with just 3% of those with type 2 diabetes. In contrast, 60% of the type 2 patients had three or more risk factors, compared with just 13% of the nondiabetic controls. Those with type 2 diabetes had a mean of 2.9 CV risk factors each, compared with 1 for the controls.

The type 2 group also had a less favorable profile of nontraditional CV risk factors, including significantly lower levels of adiponectin and LDL particle density, and higher levels of apolipoprotein B, fibrinogen, and interleukin-6.

In a series of multiple linear regression models, adjustment for differences in obesity accounted for the differences between the type 2 group and the controls in HDL cholesterol, systolic blood pressure, and adiponectin, while adjustment for hemoglobin A_1c between the groups accounted for the differences in apolipoprotein B and LDL particle size. Adjustment for both obesity and HbA_1c accounted for the difference in triglycerides.

ROME — Youth with type 2 diabetes had an average of nearly three cardiovascular risk factors each, compared with just one among healthy controls in an analysis of 295 participants in a large, multicenter, U.S. case-control study.

The data come from 106 patients with type 2 diabetes and 189 healthy controls (matched for age, sex, and race/ethnicity) recruited by primary care providers at two sites (Colorado and South Carolina) of the six sites participating in the federally-funded SEARCH for Diabetes in Youth, a study designed to investigate the prevalence and characteristics of diabetes among individuals aged younger than 20 years (www.searchfordiabetes.org

The current analysis, one of the first to look specifically at cardiovascular (CV) risk in youth with type 2 diabetes, also revealed that not all of the risk factors could be accounted for by increased obesity and/or hyperglycemia. “We believe that our data support the statement that early prevention and treatment strategies aimed at reducing the prevalence of cardiovascular risk factors in youth with type 2 diabetes mellitus are urgently needed,” Dr. Dana Dabelea said at the annual meeting of the European Association for the Study of Diabetes.

Participants were aged 10–22 years, with a mean of 16 years for the diabetic group and 14 years for the controls. (This was a statistically significant difference, despite attempts to age-match.) Duration of diabetes in the type 2 group was 1.5 years. Females comprised 69% of the diabetic group and 60% of controls, not significantly different, said Dr. Dabelea, director of the epidemiology PhD program at the University of Colorado, Denver, and a principal investigator at the SEARCH Colorado site.

The type 2 group was significantly more likely than were the controls to be African American (55% vs. 29%) and less likely to be non-Hispanic white (28% vs. 54%). The proportion of Hispanics was 17% in both groups. Body mass index was significantly greater among the youth with diabetes (35 vs. 24 kg/m

Consumption of saturated fat as a percent of total daily calories was slightly higher in the type 2 group, while the amount of daily physical activity was lower, but these did not reach statistical significance.

Highly statistically significant differences were seen between the two groups in the proportions—adjusted for age and race/ethnicity—who had hypertension, defined as systolic or diastolic blood pressure of 95th percentile or greater for age, sex, height, or medication (27% in the type 2 group vs. 5% of controls), low HDL cholesterol, defined as 35 mg/dL or below (25% of the type 2 group vs. 5% of controls) and high triglycerides, of 150 mg/dL or higher (27% vs. 6%).

Also highly significantly different were the proportions who were obese, defined as 95th percentile or greater BMI for age and sex (86% vs. 26%) and those who had a large waist circumference, defined as 90th percentile or greater for age and sex (82% vs. 22%).

Elevated albumin/creatinine ratio of 30 mcg/mg or greater was present in 17% of the type 2 group vs. 7% of controls, of borderline significance. The proportions of patients with high LDL cholesterol (130 mg/dL or greater) and who were current smokers were not significantly different, she said.

Nearly half (45%) of the controls had none of these CV risk factors, compared with just 3% of those with type 2 diabetes. In contrast, 60% of the type 2 patients had three or more risk factors, compared with just 13% of the nondiabetic controls. Those with type 2 diabetes had a mean of 2.9 CV risk factors each, compared with 1 for the controls.

The type 2 group also had a less favorable profile of nontraditional CV risk factors, including significantly lower levels of adiponectin and LDL particle density, and higher levels of apolipoprotein B, fibrinogen, and interleukin-6.

In a series of multiple linear regression models, adjustment for differences in obesity accounted for the differences between the type 2 group and the controls in HDL cholesterol, systolic blood pressure, and adiponectin, while adjustment for hemoglobin A_1c between the groups accounted for the differences in apolipoprotein B and LDL particle size. Adjustment for both obesity and HbA_1c accounted for the difference in triglycerides.

The Food and Drug Administration will no longer issue “approvable” or “not approvable” letters when a drug application is not approved, but will instead issue a “complete response” letter at the end of the review period, the agency announced in July.

“These new regulations will help the FDA adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form,” Dr. Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, said in a written statement.

Currently, when assessing new drug and generic drug applications, the FDA can respond to a sponsor in one of three types of letters: an “approval” letter, meaning the drug has met agency standards for safety and efficacy and can be marketed for sale in the United States; an “approvable” letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to the labeling); or a “not approvable” letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before approval.

A “complete response” letter, which will replace options 2 and 3, will be issued to inform the company that the review period for a drug is complete and that the application is not yet ready for approval, the statement said. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to prepare the application for approval. The way that the FDA communicates its decisions to approve an application—option 1—will not change.

The move, which went into effect in late summer, brings the process for communication about drug licensing applications in line with that of biologics, for which “complete response” letters have been used since 1998. The revision should not affect the overall time it takes the FDA to review new or generic drug applications or biologic license applications, according to the agency.

Other changes involve modifications to the schedule for reviewing amendments to licensing applications, classification of responses to a complete response letter, timelines for submitting a response to a complete response letter and administrative actions for a failure to respond, and definition of an efficacy supplement.

The Food and Drug Administration will no longer issue “approvable” or “not approvable” letters when a drug application is not approved, but will instead issue a “complete response” letter at the end of the review period, the agency announced in July.

“These new regulations will help the FDA adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form,” Dr. Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, said in a written statement.

Currently, when assessing new drug and generic drug applications, the FDA can respond to a sponsor in one of three types of letters: an “approval” letter, meaning the drug has met agency standards for safety and efficacy and can be marketed for sale in the United States; an “approvable” letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to the labeling); or a “not approvable” letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before approval.

A “complete response” letter, which will replace options 2 and 3, will be issued to inform the company that the review period for a drug is complete and that the application is not yet ready for approval, the statement said. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to prepare the application for approval. The way that the FDA communicates its decisions to approve an application—option 1—will not change.

The move, which went into effect in late summer, brings the process for communication about drug licensing applications in line with that of biologics, for which “complete response” letters have been used since 1998. The revision should not affect the overall time it takes the FDA to review new or generic drug applications or biologic license applications, according to the agency.

Other changes involve modifications to the schedule for reviewing amendments to licensing applications, classification of responses to a complete response letter, timelines for submitting a response to a complete response letter and administrative actions for a failure to respond, and definition of an efficacy supplement.

The Food and Drug Administration will no longer issue “approvable” or “not approvable” letters when a drug application is not approved, but will instead issue a “complete response” letter at the end of the review period, the agency announced in July.

“These new regulations will help the FDA adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form,” Dr. Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, said in a written statement.

Currently, when assessing new drug and generic drug applications, the FDA can respond to a sponsor in one of three types of letters: an “approval” letter, meaning the drug has met agency standards for safety and efficacy and can be marketed for sale in the United States; an “approvable” letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to the labeling); or a “not approvable” letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before approval.

A “complete response” letter, which will replace options 2 and 3, will be issued to inform the company that the review period for a drug is complete and that the application is not yet ready for approval, the statement said. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to prepare the application for approval. The way that the FDA communicates its decisions to approve an application—option 1—will not change.

The move, which went into effect in late summer, brings the process for communication about drug licensing applications in line with that of biologics, for which “complete response” letters have been used since 1998. The revision should not affect the overall time it takes the FDA to review new or generic drug applications or biologic license applications, according to the agency.

Other changes involve modifications to the schedule for reviewing amendments to licensing applications, classification of responses to a complete response letter, timelines for submitting a response to a complete response letter and administrative actions for a failure to respond, and definition of an efficacy supplement.

WASHINGTON — The development of acute coronary syndrome was eight times more common among 206 patients hospitalized with community-acquired bacterial pneumonia than among 395 hospitalized controls in a 7-year study.

Moreover, the risk of having an acute coronary event was 45 times greater among the pneumonia patients in the first 15 days after admission—and more than 100 times greater during the first 3 days—than it was during either the previous or subsequent year.

“The association between bacterial pneumonia and the development of ACS is so striking that a causal relation is suggested,” Dr. Vicente Corrales-Medina and his associates wrote in a poster presented at the jointly-held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Several previous studies have suggested an association between acute infections—including those of the respiratory, gastrointestinal, and urinary tract—and the occurrence of ACS in the days and weeks after the infection. Most of those studies have not clearly defined or confirmed the infections, however, Dr. Corrales-Medina of the infectious diseases department of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, said in an interview.

Researchers in the current study enrolled patients hospitalized at the Houston VA Medical Center during 2000–2006. Study participants had either clinical and radiologic evidence for pneumonia and one blood culture yielding Streptococcus pneumoniae or Haemophilus influenzae, or a clinical syndrome of pneumonia, radiologic documentation of a new pulmonary infiltrate, a sputum sample showing more than 10 inflammatory cells per epithelial cell with predominance of gram-positive cocci in pairs or gram-negative coccobacilli, and a culture yielding pneumococci or H. influenzae with no other likely bacterial pathogens.

Case controls were patients whose reason for admission was not an elective or therapeutic procedure and whose admission diagnosis was different from pneumonia or ACS. Final diagnoses of ACS were determined by a senior cardiologist.

Of the 206 cases of pneumonia, 144 were due to S. pneumoniae and 62 to H. influenzae.

There were 22 (10.7%) cases of ACS in the group with community-acquired pneumonia (CAP) and 6 (1.5%) in the controls, a significant difference with an odds ratio of 7.8. The odds ratio was 7.0 for cases of CAP caused by S. pneumoniae and 9.6 for those caused by H. influenzae.

Dr. Corrales-Medina stated that he had no financial disclosures.

WASHINGTON — The development of acute coronary syndrome was eight times more common among 206 patients hospitalized with community-acquired bacterial pneumonia than among 395 hospitalized controls in a 7-year study.

Moreover, the risk of having an acute coronary event was 45 times greater among the pneumonia patients in the first 15 days after admission—and more than 100 times greater during the first 3 days—than it was during either the previous or subsequent year.

“The association between bacterial pneumonia and the development of ACS is so striking that a causal relation is suggested,” Dr. Vicente Corrales-Medina and his associates wrote in a poster presented at the jointly-held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Several previous studies have suggested an association between acute infections—including those of the respiratory, gastrointestinal, and urinary tract—and the occurrence of ACS in the days and weeks after the infection. Most of those studies have not clearly defined or confirmed the infections, however, Dr. Corrales-Medina of the infectious diseases department of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, said in an interview.

Researchers in the current study enrolled patients hospitalized at the Houston VA Medical Center during 2000–2006. Study participants had either clinical and radiologic evidence for pneumonia and one blood culture yielding Streptococcus pneumoniae or Haemophilus influenzae, or a clinical syndrome of pneumonia, radiologic documentation of a new pulmonary infiltrate, a sputum sample showing more than 10 inflammatory cells per epithelial cell with predominance of gram-positive cocci in pairs or gram-negative coccobacilli, and a culture yielding pneumococci or H. influenzae with no other likely bacterial pathogens.

Case controls were patients whose reason for admission was not an elective or therapeutic procedure and whose admission diagnosis was different from pneumonia or ACS. Final diagnoses of ACS were determined by a senior cardiologist.

Of the 206 cases of pneumonia, 144 were due to S. pneumoniae and 62 to H. influenzae.

There were 22 (10.7%) cases of ACS in the group with community-acquired pneumonia (CAP) and 6 (1.5%) in the controls, a significant difference with an odds ratio of 7.8. The odds ratio was 7.0 for cases of CAP caused by S. pneumoniae and 9.6 for those caused by H. influenzae.

Dr. Corrales-Medina stated that he had no financial disclosures.

WASHINGTON — The development of acute coronary syndrome was eight times more common among 206 patients hospitalized with community-acquired bacterial pneumonia than among 395 hospitalized controls in a 7-year study.

Moreover, the risk of having an acute coronary event was 45 times greater among the pneumonia patients in the first 15 days after admission—and more than 100 times greater during the first 3 days—than it was during either the previous or subsequent year.

“The association between bacterial pneumonia and the development of ACS is so striking that a causal relation is suggested,” Dr. Vicente Corrales-Medina and his associates wrote in a poster presented at the jointly-held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Several previous studies have suggested an association between acute infections—including those of the respiratory, gastrointestinal, and urinary tract—and the occurrence of ACS in the days and weeks after the infection. Most of those studies have not clearly defined or confirmed the infections, however, Dr. Corrales-Medina of the infectious diseases department of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, said in an interview.

Researchers in the current study enrolled patients hospitalized at the Houston VA Medical Center during 2000–2006. Study participants had either clinical and radiologic evidence for pneumonia and one blood culture yielding Streptococcus pneumoniae or Haemophilus influenzae, or a clinical syndrome of pneumonia, radiologic documentation of a new pulmonary infiltrate, a sputum sample showing more than 10 inflammatory cells per epithelial cell with predominance of gram-positive cocci in pairs or gram-negative coccobacilli, and a culture yielding pneumococci or H. influenzae with no other likely bacterial pathogens.

Case controls were patients whose reason for admission was not an elective or therapeutic procedure and whose admission diagnosis was different from pneumonia or ACS. Final diagnoses of ACS were determined by a senior cardiologist.

Of the 206 cases of pneumonia, 144 were due to S. pneumoniae and 62 to H. influenzae.

There were 22 (10.7%) cases of ACS in the group with community-acquired pneumonia (CAP) and 6 (1.5%) in the controls, a significant difference with an odds ratio of 7.8. The odds ratio was 7.0 for cases of CAP caused by S. pneumoniae and 9.6 for those caused by H. influenzae.

Dr. Corrales-Medina stated that he had no financial disclosures.

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy.

Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, professor of epidemiology at the University of Pittsburgh.

Investigators examined follow-up data for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) and for subjects participating in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977-86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994.

The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years.

The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

On the basis of data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%).

In terms of nephropathy outcomes (defined as having albuminuria greater than 300 mg/24 hours or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively.

Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/ EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially,” Dr. Orchard concluded.

The improvements seen in the recent cohorts may underestimate the improvements that are currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” he continued.

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy.

Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, professor of epidemiology at the University of Pittsburgh.

Investigators examined follow-up data for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) and for subjects participating in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977-86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994.

The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years.

The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

On the basis of data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%).

In terms of nephropathy outcomes (defined as having albuminuria greater than 300 mg/24 hours or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively.

Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/ EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially,” Dr. Orchard concluded.

The improvements seen in the recent cohorts may underestimate the improvements that are currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” he continued.

ROME — The long-term outlook for patients with type 1 diabetes today is improving substantially and is projected to improve further now that intensive therapy is used more widely.

That conclusion is based on an analysis of epidemiologic data from two major studies involving three patient cohorts with different durations of intensive therapy.

Results were presented by Dr. Trevor J. Orchard at the annual meeting of the European Association for the Study of Diabetes.

“Recent reports from Europe and North America show declines in incidences of complications, particularly in renal disease, in type 1 diabetes mellitus. However, the full potential of improved care through intensive therapy and decreasing hemoglobin A_1c levels has not been well recognized, particularly by insurers,” said Dr. Orchard, professor of epidemiology at the University of Pittsburgh.

Investigators examined follow-up data for both the intensive and conventional therapy groups from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) and for subjects participating in the community-based Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

The DCCT, conducted between 1984 and 1993, was the landmark study that demonstrated that intensive glucose control (achieved via three or more daily insulin injections or an insulin pump) significantly delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy, compared with conventional (two injections/day) therapy (N. Engl. J. Med. 1993;329:977-86).

The 1,441 patients randomized in DCCT are now being followed in EDIC, which began in 1994.

The 730 patients who had been randomized to conventional treatment in DCCT were offered intensive therapy upon transitioning to EDIC. Mean follow-up duration is now 19 years. The EDC (Pittsburgh) cohort comprised 658 patients with childhood-onset type 1 diabetes who were first examined between 1986 and 1988, when their mean age was 28 years and mean diabetes duration was 19 years.

The study is now in its 20th year of follow-up, Dr. Orchard said.

The proportion of each group's entire diabetes duration spent on intensive therapy is now 74% for the 620 patients from the DCCT/EDIC intensive therapy cohort included in the current analysis, 42% for the 606 from the conventional DCCT/EDIC cohort, and 26% for the 161 from the EDC population. The DCCT/EDIC conventional treatment group and the EDC group reflect current clinical care outcomes, while the outcomes for the DCCT/EDIC intensive treatment group represent what can be expected of diabetes care going forward, he explained.

On the basis of data obtained at clinical follow-ups done between 2004 and 2007, the estimated 30-year cumulative incidence of proliferative retinopathy is 21.1% for the DCCT/EDIC intensive group—less than half that of the DCCT/EDIC conventional patients (49.7%) and the EDC group (47%).

In terms of nephropathy outcomes (defined as having albuminuria greater than 300 mg/24 hours or being on dialysis), projected 30-year cumulative incidence for the intensive group is just 8.6%, compared with 25.1% and 17% for the conventional and EDC groups, respectively.

Cardiovascular disease 30-year estimates are 8.5% for the intensive DCCT/ EDIC patients vs. 14% for both of the other cohorts.

“The clinical course of type 1 diabetes and development of complications are improving substantially,” Dr. Orchard concluded.

The improvements seen in the recent cohorts may underestimate the improvements that are currently achievable as cohorts accumulate a greater proportion of their duration on intensive therapy,” he continued.

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% 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].”

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, 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 mandated reporting for 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 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.

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% 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].”

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, 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 mandated reporting for 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 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.

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% 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].”

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, 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 mandated reporting for 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 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.

ROME — Treatment of polycystic ovary syndrome with exenatide plus metformin was more effective than either medication alone in improving menstrual cycle frequency and in ameliorating hormonal and metabolic derangements, according to a study of 60 patients.

The study findings were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Ted Okerson of Amylin Pharmaceuticals Inc. on behalf of the scheduled presenter, Dr. Rajat Bhushan of the Metabolic Center of Louisiana Research Foundation, Baton Rouge, who was unable to attend the meeting because of a hurricane. Dr. Karen Elkind-Hirsch of the same institution was the principal author of the study, published in the Journal of Clinical Endocrinology and Metabolism (2008;93:2670-8).

Metformin has been shown to reduce insulin resistance and androgen levels while increasing ovulation in women with polycystic ovary syndrome (PCOS). However, metformin does not alter insulin secretion. Exenatide (Byetta), used to treat type 2 diabetes, has been shown to restore first- and second-phase insulin secretion, which is attenuated in women with PCOS, as well as to promote weight loss, thereby potentially further improving insulin sensitivity, Dr. Okerson said.

An open-label, prospective 24-week pilot study of 60 obese oligo-ovulatory women with PCOS was funded by a grant from Amylin Pharmaceuticals and Eli Lilly & Co. In the study, 40 white and 20 African American women with PCOS were randomized to receive either 1,000 mg metformin twice daily, exenatide 10 mcg twice daily, or a combination of the two, for 24 weeks. All were aged 18-40, with a body mass index above 27 kg/m

Menstrual cycle frequency, the primary study end point, was significantly increased in all treatment groups at 24 weeks and to a significantly greater degree with the combination, compared with metformin alone. The proportion of normal cycles in the group increased from a mean of 22% at baseline to 57% with exenatide alone, from 21% to 49% with metformin alone, and from 29% to 83% with both drugs. Ovulatory rates also improved with all three regimens, but significantly more so with the combination. Ovulation occurred in 12 of the combination patients (86%), compared with 7 who received exenatide alone (50%) and 4 with metformin alone (29%).

Body weight changes were significant in both groups receiving exenatide, but not in those receiving metformin alone. At 24 weeks, mean weight loss was 6 kg in the combination group and 3.2 kg with exenatide alone, vs. just 1.6 kg with metformin alone. Similar reductions were seen in body mass index. Abdominal girth diminished slightly in both exenatide groups but increased slightly between weeks 12 and 24 among the metformin-alone patients, Dr. Okerson reported.

Total testosterone was significantly decreased from baseline in all treatment groups, by 10.2 ng/dL with exenatide alone, 3.6 ng/dL with metformin alone, and 18.4 ng/dL with the combination. The free androgen index was significantly more reduced with the combination, compared with metformin alone but not compared with exenatide alone. Levels of sex hormone-binding globulin were increased, but not significantly, with all treatments, while levels of dehydroepiandrosterone sulfate and thyroid-stimulating hormone were not significantly altered in any group.

Insulin sensitivity improved significantly with all treatments, and was significantly higher in the combination group than in the metformin group at 24 weeks. After therapy, the calculated mean insulin secretion sensitivity index was 516 with combination therapy, 395 with exenatide alone, and 232 with metformin alone. Total cholesterol and triglycerides decreased significantly with combination therapy vs. metformin monotherapy, which did not consistently improve those levels, while HDL and LDL cholesterol levels did not change significantly with treatment. Adiponectin levels increased significantly with all treatments, while other inflammatory markers did not change.

The most common adverse events were mild or moderate gastrointestinal problems, including nausea, which occurred in 15% with exenatide alone, 20% with metformin alone, and 45% with the combination.

ROME — Treatment of polycystic ovary syndrome with exenatide plus metformin was more effective than either medication alone in improving menstrual cycle frequency and in ameliorating hormonal and metabolic derangements, according to a study of 60 patients.

The study findings were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Ted Okerson of Amylin Pharmaceuticals Inc. on behalf of the scheduled presenter, Dr. Rajat Bhushan of the Metabolic Center of Louisiana Research Foundation, Baton Rouge, who was unable to attend the meeting because of a hurricane. Dr. Karen Elkind-Hirsch of the same institution was the principal author of the study, published in the Journal of Clinical Endocrinology and Metabolism (2008;93:2670-8).

Metformin has been shown to reduce insulin resistance and androgen levels while increasing ovulation in women with polycystic ovary syndrome (PCOS). However, metformin does not alter insulin secretion. Exenatide (Byetta), used to treat type 2 diabetes, has been shown to restore first- and second-phase insulin secretion, which is attenuated in women with PCOS, as well as to promote weight loss, thereby potentially further improving insulin sensitivity, Dr. Okerson said.

An open-label, prospective 24-week pilot study of 60 obese oligo-ovulatory women with PCOS was funded by a grant from Amylin Pharmaceuticals and Eli Lilly & Co. In the study, 40 white and 20 African American women with PCOS were randomized to receive either 1,000 mg metformin twice daily, exenatide 10 mcg twice daily, or a combination of the two, for 24 weeks. All were aged 18-40, with a body mass index above 27 kg/m

Menstrual cycle frequency, the primary study end point, was significantly increased in all treatment groups at 24 weeks and to a significantly greater degree with the combination, compared with metformin alone. The proportion of normal cycles in the group increased from a mean of 22% at baseline to 57% with exenatide alone, from 21% to 49% with metformin alone, and from 29% to 83% with both drugs. Ovulatory rates also improved with all three regimens, but significantly more so with the combination. Ovulation occurred in 12 of the combination patients (86%), compared with 7 who received exenatide alone (50%) and 4 with metformin alone (29%).

Body weight changes were significant in both groups receiving exenatide, but not in those receiving metformin alone. At 24 weeks, mean weight loss was 6 kg in the combination group and 3.2 kg with exenatide alone, vs. just 1.6 kg with metformin alone. Similar reductions were seen in body mass index. Abdominal girth diminished slightly in both exenatide groups but increased slightly between weeks 12 and 24 among the metformin-alone patients, Dr. Okerson reported.

Total testosterone was significantly decreased from baseline in all treatment groups, by 10.2 ng/dL with exenatide alone, 3.6 ng/dL with metformin alone, and 18.4 ng/dL with the combination. The free androgen index was significantly more reduced with the combination, compared with metformin alone but not compared with exenatide alone. Levels of sex hormone-binding globulin were increased, but not significantly, with all treatments, while levels of dehydroepiandrosterone sulfate and thyroid-stimulating hormone were not significantly altered in any group.

Insulin sensitivity improved significantly with all treatments, and was significantly higher in the combination group than in the metformin group at 24 weeks. After therapy, the calculated mean insulin secretion sensitivity index was 516 with combination therapy, 395 with exenatide alone, and 232 with metformin alone. Total cholesterol and triglycerides decreased significantly with combination therapy vs. metformin monotherapy, which did not consistently improve those levels, while HDL and LDL cholesterol levels did not change significantly with treatment. Adiponectin levels increased significantly with all treatments, while other inflammatory markers did not change.

The most common adverse events were mild or moderate gastrointestinal problems, including nausea, which occurred in 15% with exenatide alone, 20% with metformin alone, and 45% with the combination.

ROME — Treatment of polycystic ovary syndrome with exenatide plus metformin was more effective than either medication alone in improving menstrual cycle frequency and in ameliorating hormonal and metabolic derangements, according to a study of 60 patients.

The study findings were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Ted Okerson of Amylin Pharmaceuticals Inc. on behalf of the scheduled presenter, Dr. Rajat Bhushan of the Metabolic Center of Louisiana Research Foundation, Baton Rouge, who was unable to attend the meeting because of a hurricane. Dr. Karen Elkind-Hirsch of the same institution was the principal author of the study, published in the Journal of Clinical Endocrinology and Metabolism (2008;93:2670-8).

Metformin has been shown to reduce insulin resistance and androgen levels while increasing ovulation in women with polycystic ovary syndrome (PCOS). However, metformin does not alter insulin secretion. Exenatide (Byetta), used to treat type 2 diabetes, has been shown to restore first- and second-phase insulin secretion, which is attenuated in women with PCOS, as well as to promote weight loss, thereby potentially further improving insulin sensitivity, Dr. Okerson said.

An open-label, prospective 24-week pilot study of 60 obese oligo-ovulatory women with PCOS was funded by a grant from Amylin Pharmaceuticals and Eli Lilly & Co. In the study, 40 white and 20 African American women with PCOS were randomized to receive either 1,000 mg metformin twice daily, exenatide 10 mcg twice daily, or a combination of the two, for 24 weeks. All were aged 18-40, with a body mass index above 27 kg/m

Menstrual cycle frequency, the primary study end point, was significantly increased in all treatment groups at 24 weeks and to a significantly greater degree with the combination, compared with metformin alone. The proportion of normal cycles in the group increased from a mean of 22% at baseline to 57% with exenatide alone, from 21% to 49% with metformin alone, and from 29% to 83% with both drugs. Ovulatory rates also improved with all three regimens, but significantly more so with the combination. Ovulation occurred in 12 of the combination patients (86%), compared with 7 who received exenatide alone (50%) and 4 with metformin alone (29%).

Body weight changes were significant in both groups receiving exenatide, but not in those receiving metformin alone. At 24 weeks, mean weight loss was 6 kg in the combination group and 3.2 kg with exenatide alone, vs. just 1.6 kg with metformin alone. Similar reductions were seen in body mass index. Abdominal girth diminished slightly in both exenatide groups but increased slightly between weeks 12 and 24 among the metformin-alone patients, Dr. Okerson reported.

Total testosterone was significantly decreased from baseline in all treatment groups, by 10.2 ng/dL with exenatide alone, 3.6 ng/dL with metformin alone, and 18.4 ng/dL with the combination. The free androgen index was significantly more reduced with the combination, compared with metformin alone but not compared with exenatide alone. Levels of sex hormone-binding globulin were increased, but not significantly, with all treatments, while levels of dehydroepiandrosterone sulfate and thyroid-stimulating hormone were not significantly altered in any group.

Insulin sensitivity improved significantly with all treatments, and was significantly higher in the combination group than in the metformin group at 24 weeks. After therapy, the calculated mean insulin secretion sensitivity index was 516 with combination therapy, 395 with exenatide alone, and 232 with metformin alone. Total cholesterol and triglycerides decreased significantly with combination therapy vs. metformin monotherapy, which did not consistently improve those levels, while HDL and LDL cholesterol levels did not change significantly with treatment. Adiponectin levels increased significantly with all treatments, while other inflammatory markers did not change.

The most common adverse events were mild or moderate gastrointestinal problems, including nausea, which occurred in 15% with exenatide alone, 20% with metformin alone, and 45% with the combination.

ROME — The investigational, once-daily, human glucagon-like peptide-1 analog, liraglutide, produced a 1.5 percentage point drop in hemoglobin A_1c, as well as significant drops in body weight and blood pressure, in a study of patients with type 2 diabetes who were also taking metformin and rosiglitazone.

The findings of this 26-week phase IIIA randomized, placebo-controlled trial of 533 patients were reported by Dr. Bernard Zinman at a press briefing held during the annual meeting of the European Association for the Study of Diabetes.

The LEAD (Liraglutide Efficacy and Action in Diabetes) 4 trial, sponsored by Novo-Nordisk, comprised 533 subjects with a mean age of 55 years, mean body mass index of 33.5 kg/m

At 26 weeks, HbA_1c levels had dropped from baseline by a statistically significant 1.5 percentage points in both the 1.2-mg and 1.8-mg liraglutide groups, to 7.0% and 7.1%, respectively, compared with a drop of just 0.5 percentage point (to 7.9%) in the placebo group.

The proportions who achieved an HbA_1c of less than 7.0% were 58% of those on the 1.2-mg dose and 54% of those on the 1.8-mg dose, compared with just 28% of the placebo group.

More than a third of both groups (36% of those on the 1.2-mg dose and 37% of those on the 1.8-mg dose) achieved HbA_1c levels of 6.5% or less.

Fasting plasma glucose (FPG) levels also dropped significantly with both liraglutide doses (by 2.2 mmol/L with 1.2 mg and by 2.4 mmol/L with 1.8 mg) to final FPG levels of 7.7 mmol/L and 7.6 mmol/L, respectively. The FPG drop in the placebo subjects was just 0.4 mmol/L (to 9.5 mmol/L).

Body weight dropped by 1.02 kg with the 1.2-mg dose and by 2.02 kg with the 1.8-mg dose, both statistically significant changes.

Mean systolic blood pressure levels were reduced by 6.7 mm Hg with the 1.2-mg dose and by 5.6 mm Hg with the 1.8-mg dose, compared with just 1.1 mm Hg with placebo, which were also statistically significant differences.

No major hypoglycemic episodes were reported during the study. Minor hypoglycemia (defined as less than 3.1 mmol/L), occurred in 9% of the 1.2-mg group, 8% of the 1.8-mg group, and 5% of the placebo group. The rate of 0.64 events per subject per year that was seen in the 1.8-mg group was statistically significant, compared with the 0.17 rate seen in the placebo group.

Nausea was the most common adverse event reported, occurring in 29% of the 1.2-mg group and 40% of the 1.8-mg group, compared with just 9% with placebo. Nausea occurred early in the treatment regimen and returned to placebo levels after 16 weeks.

On May 23, 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the United States, as well as a marketing authorization application to the European Medicines Agency for the approval of liraglutide for the treatment of type 2 diabetes. If approved, liraglutide would be the first human-derived GLP-1 analog.

Exenatide (Byetta), the GLP-1 mimetic currently on the market, is derived from the salivary gland of a lizard.

Novo-Nordisk has completed a head-to-head comparison study that compares liraglutide with exenatide, both combined with metformin and sulfonylurea. Those results will be presented this month at the Canadian Diabetes Association annual meeting in Quebec.

Dr. Zinman is a consultant for Novo Nordisk Inc.

ROME — The investigational, once-daily, human glucagon-like peptide-1 analog, liraglutide, produced a 1.5 percentage point drop in hemoglobin A_1c, as well as significant drops in body weight and blood pressure, in a study of patients with type 2 diabetes who were also taking metformin and rosiglitazone.

The findings of this 26-week phase IIIA randomized, placebo-controlled trial of 533 patients were reported by Dr. Bernard Zinman at a press briefing held during the annual meeting of the European Association for the Study of Diabetes.

The LEAD (Liraglutide Efficacy and Action in Diabetes) 4 trial, sponsored by Novo-Nordisk, comprised 533 subjects with a mean age of 55 years, mean body mass index of 33.5 kg/m

At 26 weeks, HbA_1c levels had dropped from baseline by a statistically significant 1.5 percentage points in both the 1.2-mg and 1.8-mg liraglutide groups, to 7.0% and 7.1%, respectively, compared with a drop of just 0.5 percentage point (to 7.9%) in the placebo group.

The proportions who achieved an HbA_1c of less than 7.0% were 58% of those on the 1.2-mg dose and 54% of those on the 1.8-mg dose, compared with just 28% of the placebo group.

More than a third of both groups (36% of those on the 1.2-mg dose and 37% of those on the 1.8-mg dose) achieved HbA_1c levels of 6.5% or less.

Fasting plasma glucose (FPG) levels also dropped significantly with both liraglutide doses (by 2.2 mmol/L with 1.2 mg and by 2.4 mmol/L with 1.8 mg) to final FPG levels of 7.7 mmol/L and 7.6 mmol/L, respectively. The FPG drop in the placebo subjects was just 0.4 mmol/L (to 9.5 mmol/L).

Body weight dropped by 1.02 kg with the 1.2-mg dose and by 2.02 kg with the 1.8-mg dose, both statistically significant changes.

Mean systolic blood pressure levels were reduced by 6.7 mm Hg with the 1.2-mg dose and by 5.6 mm Hg with the 1.8-mg dose, compared with just 1.1 mm Hg with placebo, which were also statistically significant differences.

No major hypoglycemic episodes were reported during the study. Minor hypoglycemia (defined as less than 3.1 mmol/L), occurred in 9% of the 1.2-mg group, 8% of the 1.8-mg group, and 5% of the placebo group. The rate of 0.64 events per subject per year that was seen in the 1.8-mg group was statistically significant, compared with the 0.17 rate seen in the placebo group.

Nausea was the most common adverse event reported, occurring in 29% of the 1.2-mg group and 40% of the 1.8-mg group, compared with just 9% with placebo. Nausea occurred early in the treatment regimen and returned to placebo levels after 16 weeks.

On May 23, 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the United States, as well as a marketing authorization application to the European Medicines Agency for the approval of liraglutide for the treatment of type 2 diabetes. If approved, liraglutide would be the first human-derived GLP-1 analog.

Exenatide (Byetta), the GLP-1 mimetic currently on the market, is derived from the salivary gland of a lizard.

Novo-Nordisk has completed a head-to-head comparison study that compares liraglutide with exenatide, both combined with metformin and sulfonylurea. Those results will be presented this month at the Canadian Diabetes Association annual meeting in Quebec.

Dr. Zinman is a consultant for Novo Nordisk Inc.

ROME — The investigational, once-daily, human glucagon-like peptide-1 analog, liraglutide, produced a 1.5 percentage point drop in hemoglobin A_1c, as well as significant drops in body weight and blood pressure, in a study of patients with type 2 diabetes who were also taking metformin and rosiglitazone.

The findings of this 26-week phase IIIA randomized, placebo-controlled trial of 533 patients were reported by Dr. Bernard Zinman at a press briefing held during the annual meeting of the European Association for the Study of Diabetes.

The LEAD (Liraglutide Efficacy and Action in Diabetes) 4 trial, sponsored by Novo-Nordisk, comprised 533 subjects with a mean age of 55 years, mean body mass index of 33.5 kg/m

At 26 weeks, HbA_1c levels had dropped from baseline by a statistically significant 1.5 percentage points in both the 1.2-mg and 1.8-mg liraglutide groups, to 7.0% and 7.1%, respectively, compared with a drop of just 0.5 percentage point (to 7.9%) in the placebo group.

The proportions who achieved an HbA_1c of less than 7.0% were 58% of those on the 1.2-mg dose and 54% of those on the 1.8-mg dose, compared with just 28% of the placebo group.

More than a third of both groups (36% of those on the 1.2-mg dose and 37% of those on the 1.8-mg dose) achieved HbA_1c levels of 6.5% or less.

Fasting plasma glucose (FPG) levels also dropped significantly with both liraglutide doses (by 2.2 mmol/L with 1.2 mg and by 2.4 mmol/L with 1.8 mg) to final FPG levels of 7.7 mmol/L and 7.6 mmol/L, respectively. The FPG drop in the placebo subjects was just 0.4 mmol/L (to 9.5 mmol/L).

Body weight dropped by 1.02 kg with the 1.2-mg dose and by 2.02 kg with the 1.8-mg dose, both statistically significant changes.

Mean systolic blood pressure levels were reduced by 6.7 mm Hg with the 1.2-mg dose and by 5.6 mm Hg with the 1.8-mg dose, compared with just 1.1 mm Hg with placebo, which were also statistically significant differences.

No major hypoglycemic episodes were reported during the study. Minor hypoglycemia (defined as less than 3.1 mmol/L), occurred in 9% of the 1.2-mg group, 8% of the 1.8-mg group, and 5% of the placebo group. The rate of 0.64 events per subject per year that was seen in the 1.8-mg group was statistically significant, compared with the 0.17 rate seen in the placebo group.

Nausea was the most common adverse event reported, occurring in 29% of the 1.2-mg group and 40% of the 1.8-mg group, compared with just 9% with placebo. Nausea occurred early in the treatment regimen and returned to placebo levels after 16 weeks.

On May 23, 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the United States, as well as a marketing authorization application to the European Medicines Agency for the approval of liraglutide for the treatment of type 2 diabetes. If approved, liraglutide would be the first human-derived GLP-1 analog.

Exenatide (Byetta), the GLP-1 mimetic currently on the market, is derived from the salivary gland of a lizard.

Novo-Nordisk has completed a head-to-head comparison study that compares liraglutide with exenatide, both combined with metformin and sulfonylurea. Those results will be presented this month at the Canadian Diabetes Association annual meeting in Quebec.

Dr. Zinman is a consultant for Novo Nordisk Inc.

Pramlintide treatment combined with lifestyle intervention resulted in sustained weight loss at 12 months in a single-blind, placebo-controlled extension study.

Pramlintide (Symlin) is an injectable synthetic analogue of human amylin, a peptide hormone that is naturally cosecreted with insulin in response to meals. Pramlintide has been shown to reduce caloric intake and promote weight loss in obese individuals.

The drug has been approved for the treatment of type 1 and type 2 diabetes and is currently under investigation by its manufacturer Amylin as a potential treatment for obesity.

In the company's initial 4-month randomized, double-blind, placebo-controlled dose-escalation study conducted at 24 centers, 411 obese subjects were randomized to receive placebo three times daily or pramlintide in doses of 120, 240, or 360 mcg either two or three times daily. (Those participants randomized to twice-daily pramlintide received placebo at midday meals.) All subjects participated in a lifestyle intervention program in which they were encouraged to reduce their caloric intake by 500 kcal/day and to increase their steps to 10,000/day with the aid of a digital pedometer.

Subjects were nondiabetic adults aged 18–70 years with a body mass index between 30 and 50 kg/m

At 4 months, weight loss in the evaluable pramlintide groups ranged from 3.9 to 5.7 kg, compared with 2.6 kg in the placebo group. The results were significant for the 120-mcg b.i.d. and 360-mcg t.i.d. and b.i.d. groups, compared with placebo. Within those arms, 44%–47% of evaluable participants achieved a weight loss of 5% or greater, compared with just 28% of the placebo participants. Reductions in weight appeared to be dose-dependent for the pramlintide twice-daily but not the thrice-daily arms, said Dr. Smith, of the Pennington Biomedical Research Center, Baton Rouge, La.

In the 8-month single-blind extension, most of the placebo subjects gained weight while all the pramlintide subjects except for the lowest dose (120 mcg) either maintained their weight or continued to lose. Excluding that one group, weight loss from baseline to month 12 ranged from 6.0 to 7.9 kg among the evaluable subjects, compared with 1.1 kg with placebo. Weight loss was statistically significant for the thrice-daily 120-, 240- and 360-mcg groups and the twice-daily 360-mcg group. In those arms, 41%–65% achieved weight loss of 5% or greater from baseline to 12 months, compared with just 18% in the placebo group.

Similar to the 4-month results, reductions at 8 months in weight appeared to be dose dependent for the twice-daily but not thrice-daily arms, the researchers said.

Pramlintide was generally safe and well-tolerated, with no novel safety concerns identified. Nausea was the only adverse event, occurring in 5% or more of study subjects and more frequently than with placebo, and was the reason for withdrawal in 12 participants. At 4 months, the incidence of nausea ranged from 9% for the 240-mcg t.i.d. group to 29% in the 360-mcg t.i.d. group, versus 2% with placebo. Nausea was generally mild to moderate and decreased over time. Weight loss was dissociated from nausea, as subjects who did not report nausea achieved body weight reductions similar to those in the overall study population, they said.

Pramlintide treatment combined with lifestyle intervention resulted in sustained weight loss at 12 months in a single-blind, placebo-controlled extension study.

Pramlintide (Symlin) is an injectable synthetic analogue of human amylin, a peptide hormone that is naturally cosecreted with insulin in response to meals. Pramlintide has been shown to reduce caloric intake and promote weight loss in obese individuals.

The drug has been approved for the treatment of type 1 and type 2 diabetes and is currently under investigation by its manufacturer Amylin as a potential treatment for obesity.

In the company's initial 4-month randomized, double-blind, placebo-controlled dose-escalation study conducted at 24 centers, 411 obese subjects were randomized to receive placebo three times daily or pramlintide in doses of 120, 240, or 360 mcg either two or three times daily. (Those participants randomized to twice-daily pramlintide received placebo at midday meals.) All subjects participated in a lifestyle intervention program in which they were encouraged to reduce their caloric intake by 500 kcal/day and to increase their steps to 10,000/day with the aid of a digital pedometer.

Subjects were nondiabetic adults aged 18–70 years with a body mass index between 30 and 50 kg/m

At 4 months, weight loss in the evaluable pramlintide groups ranged from 3.9 to 5.7 kg, compared with 2.6 kg in the placebo group. The results were significant for the 120-mcg b.i.d. and 360-mcg t.i.d. and b.i.d. groups, compared with placebo. Within those arms, 44%–47% of evaluable participants achieved a weight loss of 5% or greater, compared with just 28% of the placebo participants. Reductions in weight appeared to be dose-dependent for the pramlintide twice-daily but not the thrice-daily arms, said Dr. Smith, of the Pennington Biomedical Research Center, Baton Rouge, La.

In the 8-month single-blind extension, most of the placebo subjects gained weight while all the pramlintide subjects except for the lowest dose (120 mcg) either maintained their weight or continued to lose. Excluding that one group, weight loss from baseline to month 12 ranged from 6.0 to 7.9 kg among the evaluable subjects, compared with 1.1 kg with placebo. Weight loss was statistically significant for the thrice-daily 120-, 240- and 360-mcg groups and the twice-daily 360-mcg group. In those arms, 41%–65% achieved weight loss of 5% or greater from baseline to 12 months, compared with just 18% in the placebo group.

Similar to the 4-month results, reductions at 8 months in weight appeared to be dose dependent for the twice-daily but not thrice-daily arms, the researchers said.

Pramlintide was generally safe and well-tolerated, with no novel safety concerns identified. Nausea was the only adverse event, occurring in 5% or more of study subjects and more frequently than with placebo, and was the reason for withdrawal in 12 participants. At 4 months, the incidence of nausea ranged from 9% for the 240-mcg t.i.d. group to 29% in the 360-mcg t.i.d. group, versus 2% with placebo. Nausea was generally mild to moderate and decreased over time. Weight loss was dissociated from nausea, as subjects who did not report nausea achieved body weight reductions similar to those in the overall study population, they said.

Pramlintide treatment combined with lifestyle intervention resulted in sustained weight loss at 12 months in a single-blind, placebo-controlled extension study.

Pramlintide (Symlin) is an injectable synthetic analogue of human amylin, a peptide hormone that is naturally cosecreted with insulin in response to meals. Pramlintide has been shown to reduce caloric intake and promote weight loss in obese individuals.

The drug has been approved for the treatment of type 1 and type 2 diabetes and is currently under investigation by its manufacturer Amylin as a potential treatment for obesity.

In the company's initial 4-month randomized, double-blind, placebo-controlled dose-escalation study conducted at 24 centers, 411 obese subjects were randomized to receive placebo three times daily or pramlintide in doses of 120, 240, or 360 mcg either two or three times daily. (Those participants randomized to twice-daily pramlintide received placebo at midday meals.) All subjects participated in a lifestyle intervention program in which they were encouraged to reduce their caloric intake by 500 kcal/day and to increase their steps to 10,000/day with the aid of a digital pedometer.

Subjects were nondiabetic adults aged 18–70 years with a body mass index between 30 and 50 kg/m

At 4 months, weight loss in the evaluable pramlintide groups ranged from 3.9 to 5.7 kg, compared with 2.6 kg in the placebo group. The results were significant for the 120-mcg b.i.d. and 360-mcg t.i.d. and b.i.d. groups, compared with placebo. Within those arms, 44%–47% of evaluable participants achieved a weight loss of 5% or greater, compared with just 28% of the placebo participants. Reductions in weight appeared to be dose-dependent for the pramlintide twice-daily but not the thrice-daily arms, said Dr. Smith, of the Pennington Biomedical Research Center, Baton Rouge, La.

In the 8-month single-blind extension, most of the placebo subjects gained weight while all the pramlintide subjects except for the lowest dose (120 mcg) either maintained their weight or continued to lose. Excluding that one group, weight loss from baseline to month 12 ranged from 6.0 to 7.9 kg among the evaluable subjects, compared with 1.1 kg with placebo. Weight loss was statistically significant for the thrice-daily 120-, 240- and 360-mcg groups and the twice-daily 360-mcg group. In those arms, 41%–65% achieved weight loss of 5% or greater from baseline to 12 months, compared with just 18% in the placebo group.

Similar to the 4-month results, reductions at 8 months in weight appeared to be dose dependent for the twice-daily but not thrice-daily arms, the researchers said.

Pramlintide was generally safe and well-tolerated, with no novel safety concerns identified. Nausea was the only adverse event, occurring in 5% or more of study subjects and more frequently than with placebo, and was the reason for withdrawal in 12 participants. At 4 months, the incidence of nausea ranged from 9% for the 240-mcg t.i.d. group to 29% in the 360-mcg t.i.d. group, versus 2% with placebo. Nausea was generally mild to moderate and decreased over time. Weight loss was dissociated from nausea, as subjects who did not report nausea achieved body weight reductions similar to those in the overall study population, they said.

WASHINGTON — Significantly fewer diabetic women than men achieved target LDL cholesterol and blood pressure levels despite equivalent medication prescriptions in a study of 211 underserved inner-city and rural patients.

Evidence suggests that diabetic women carry a greater risk both for the development of cardiovascular disease (CVD) and for mortality after an acute cardiac event than do either diabetic men or women without diabetes. The finding of gender-based differences in achieving lipid and blood pressure goals suggests that sex-based physiologic differences may account for the increased cardiovascular risk in women with diabetes, Carol J. Homko, Ph.D., and her associates said in a poster presented at the annual meeting of the American Association of Diabetes Educators.

“Women with diabetes are at very high risk for CVD mortality and need to be aggressively treated to target in regards to blood pressure and cholesterol, as well as glucose,” Dr. Homko, of Temple Telemedicine Research Center, Philadelphia, said in an interview.

The patients whose charts were reviewed were enrolled in a telemedicine trial to reduce CVD risk. All had type 2 diabetes and a 10% or greater CVD risk on the Framingham 10-year absolute risk index, but they did not have overt heart disease. There were 123 women and 88 men, with no differences in mean age (61 and 59 years, respectively), body mass index (35 vs. 33 kg/m

Total cholesterol levels were significantly higher in women compared with men (201 vs. 185 mg/dL). Fewer women had total cholesterol levels of less than 200 mg/dL (57% vs. 73%), and significantly fewer were treated to an LDL cholesterol target of less than 100 mg/dL (33% vs. 48%). Similarly, mean blood pressure (BP) was higher in the women (145/79 vs. 141/83 mm Hg) and significantly fewer women achieved a target BP of less than 130/80 mm Hg (18% vs. 28%). Despite these differences, rates of insulin, aspirin, antihypertensive, and statin therapy did not differ between the two groups, the researchers reported.

It is not clear why the women in this study were less likely to be treated to target despite receiving the same pharmacotherapy that the men received. It may be that women were less compliant with their medications, although most previous studies have found women to be more compliant than men, Dr. Homko said in the interview.

“We only looked at prescription rates,” she said. “We did find that the women in our study had significantly lower rates of exercise tolerance, indicating that the men were more physically active. Therefore, the men may have experienced greater drops in BP and cholesterol because of the combination of medication and lifestyle.” And, she added, there may be some physiologic difference in response to medications between the two sexes.

The next step will be to examine gender-based differences in coagulation and endothelial function, she said.

Dr. Homko serves on the advisory board of Abbott Diabetes Care.

WASHINGTON — Significantly fewer diabetic women than men achieved target LDL cholesterol and blood pressure levels despite equivalent medication prescriptions in a study of 211 underserved inner-city and rural patients.

Evidence suggests that diabetic women carry a greater risk both for the development of cardiovascular disease (CVD) and for mortality after an acute cardiac event than do either diabetic men or women without diabetes. The finding of gender-based differences in achieving lipid and blood pressure goals suggests that sex-based physiologic differences may account for the increased cardiovascular risk in women with diabetes, Carol J. Homko, Ph.D., and her associates said in a poster presented at the annual meeting of the American Association of Diabetes Educators.

“Women with diabetes are at very high risk for CVD mortality and need to be aggressively treated to target in regards to blood pressure and cholesterol, as well as glucose,” Dr. Homko, of Temple Telemedicine Research Center, Philadelphia, said in an interview.

The patients whose charts were reviewed were enrolled in a telemedicine trial to reduce CVD risk. All had type 2 diabetes and a 10% or greater CVD risk on the Framingham 10-year absolute risk index, but they did not have overt heart disease. There were 123 women and 88 men, with no differences in mean age (61 and 59 years, respectively), body mass index (35 vs. 33 kg/m

Total cholesterol levels were significantly higher in women compared with men (201 vs. 185 mg/dL). Fewer women had total cholesterol levels of less than 200 mg/dL (57% vs. 73%), and significantly fewer were treated to an LDL cholesterol target of less than 100 mg/dL (33% vs. 48%). Similarly, mean blood pressure (BP) was higher in the women (145/79 vs. 141/83 mm Hg) and significantly fewer women achieved a target BP of less than 130/80 mm Hg (18% vs. 28%). Despite these differences, rates of insulin, aspirin, antihypertensive, and statin therapy did not differ between the two groups, the researchers reported.

It is not clear why the women in this study were less likely to be treated to target despite receiving the same pharmacotherapy that the men received. It may be that women were less compliant with their medications, although most previous studies have found women to be more compliant than men, Dr. Homko said in the interview.

“We only looked at prescription rates,” she said. “We did find that the women in our study had significantly lower rates of exercise tolerance, indicating that the men were more physically active. Therefore, the men may have experienced greater drops in BP and cholesterol because of the combination of medication and lifestyle.” And, she added, there may be some physiologic difference in response to medications between the two sexes.

The next step will be to examine gender-based differences in coagulation and endothelial function, she said.

Dr. Homko serves on the advisory board of Abbott Diabetes Care.

WASHINGTON — Significantly fewer diabetic women than men achieved target LDL cholesterol and blood pressure levels despite equivalent medication prescriptions in a study of 211 underserved inner-city and rural patients.

Evidence suggests that diabetic women carry a greater risk both for the development of cardiovascular disease (CVD) and for mortality after an acute cardiac event than do either diabetic men or women without diabetes. The finding of gender-based differences in achieving lipid and blood pressure goals suggests that sex-based physiologic differences may account for the increased cardiovascular risk in women with diabetes, Carol J. Homko, Ph.D., and her associates said in a poster presented at the annual meeting of the American Association of Diabetes Educators.

“Women with diabetes are at very high risk for CVD mortality and need to be aggressively treated to target in regards to blood pressure and cholesterol, as well as glucose,” Dr. Homko, of Temple Telemedicine Research Center, Philadelphia, said in an interview.

The patients whose charts were reviewed were enrolled in a telemedicine trial to reduce CVD risk. All had type 2 diabetes and a 10% or greater CVD risk on the Framingham 10-year absolute risk index, but they did not have overt heart disease. There were 123 women and 88 men, with no differences in mean age (61 and 59 years, respectively), body mass index (35 vs. 33 kg/m

Total cholesterol levels were significantly higher in women compared with men (201 vs. 185 mg/dL). Fewer women had total cholesterol levels of less than 200 mg/dL (57% vs. 73%), and significantly fewer were treated to an LDL cholesterol target of less than 100 mg/dL (33% vs. 48%). Similarly, mean blood pressure (BP) was higher in the women (145/79 vs. 141/83 mm Hg) and significantly fewer women achieved a target BP of less than 130/80 mm Hg (18% vs. 28%). Despite these differences, rates of insulin, aspirin, antihypertensive, and statin therapy did not differ between the two groups, the researchers reported.

It is not clear why the women in this study were less likely to be treated to target despite receiving the same pharmacotherapy that the men received. It may be that women were less compliant with their medications, although most previous studies have found women to be more compliant than men, Dr. Homko said in the interview.

“We only looked at prescription rates,” she said. “We did find that the women in our study had significantly lower rates of exercise tolerance, indicating that the men were more physically active. Therefore, the men may have experienced greater drops in BP and cholesterol because of the combination of medication and lifestyle.” And, she added, there may be some physiologic difference in response to medications between the two sexes.

The next step will be to examine gender-based differences in coagulation and endothelial function, she said.

Dr. Homko serves on the advisory board of Abbott Diabetes Care.