Kate Johnson

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

MONTREAL — Half of abnormal preoperative coagulation results normalize on repeat testing in children undergoing tonsillectomy and adenoidectomy—and among the other half that remain abnormal, 93% of the abnormalities are clinically insignificant, according to a retrospective chart review.

Despite this finding, relying on patient and family bleeding history alone is not sufficient for identifying potentially life-threatening bleeding abnormalities, said Dr. Neha Bhasin and her coauthor, who presented the findings in a poster.

The review included charts from 791 patients who were referred for further work-up over a 15-year period because routine presurgical coagulation tests revealed an elevated prothrombin time (PT) and/or activated partial thromboplastin time (aPTT), said Dr. Bhasin of Stony Brook (N.Y.) University Medical Center. On follow-up, only 3.4% of the cohort had an acute bleeding disorder, and of these patients 40% would have been missed based on personal or family bleeding history alone, she said.

“So we can't say family history is the sole criteria on which we should base an abnormal PT/PTT work-up,” Dr. Bhasin said in an interview. “You should repeat the PT/PTT before you go on a vast search. And if it is still abnormal, a full work-up is a good adjunct to family history to find out why.”

The study revealed no diagnosis for 394 (50%) of the 791 patients. For most in this subgroup, repeat testing showed their values had normalized, while for 131 the results remained abnormal for no apparent reason. “A transient lupus anticoagulant can sometimes cause an elevated PT/PTT temporarily,” she suggested.

Specific diagnoses were found to explain the abnormal results in the remaining 397 patients, but only 27 of these patients had clinically significant conditions: mild to moderate von Willebrand's disease (21), low Factor VII (3), hemophilia (2), and liver disease (1).

In the remaining 370 patients with clinically insignificant abnormalities, the most common explanation was a lupus anticoagulant (29.5%) or presumed lupus anticoagulant (36.5%), she said. Even though these findings had no acute clinical relevance to the patients, a persistent lupus anticoagulant “may be a predictor of an autoimmune process, and has been shown to represent a risk for thrombosis,” wrote the authors. “Therefore, identifying this abnormality on work-up may potentially be of future clinical significance.”

A personal or family bleeding history was documented in 256 (32%) of the 791 patients, but only 107 of them had an abnormality identified on further work-up, and only 16 of these abnormalities were clinically significant.

Additionally, 11 patients with no bleeding history were found to have clinically significant abnormalities. Therefore, relying solely on patient or family history of bleeding would have missed 41% of the 27 that were found, Dr. Bhasin said. “The presence of a positive personal and/or family history of bleeding is a strong but not absolute predictor of identifying a clinically significant bleeding disorder on further evaluation,” wrote the authors. “Therefore, routine preoperative coagulation testing serves as useful adjunct to clinical history.”

The clinical utility of performing routine preoperative coagulation testing on all children when just 3.4% will have clinically significant results “must be weighed against the risk to the patient of not identifying a hemostatic defect preoperatively,” they concluded.

Disclosures: The investigators did not report any financial conflicts of interest.

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

The pandemic influenza A(H1N1) virus has been virtually the only influenza virus circulating in the United States since it was first identified in April 2009, according to a report from Quest Diagnostics.

In an analysis of 195,000 lab tests performed at five of the company's laboratories, 99% of samples testing positive for influenza A were identified as H1N1, according to the report, titled “H1N1 Testing in America: H1N1 the Dominant Flu of 2009–2010.” “Our laboratory testing data also show an absence of influenza B viruses,” it noted. “These findings suggest the H1N1 virus has 'crowded out' other flu viruses.”

The data confirm that two waves of H1N1 infection have occurred, with no evidence of a third wave, the report's authors explained. The first wave, beginning in April or May 2009, ended in mid-August 2009. The second wave started in late August/early September 2009, and peaked in late October 2009. “Our data suggest that the return of children to school in the fall was likely the trigger for a second wave of H1N1 infection,” the report's authors wrote. “This trend—where children are the first to suffer from a new influenza virus that then spreads to other age groups—is consistent with the behavior of prior flu viruses.”

The report showed that H1N1 positivity was highest among children aged 10–14 years during both waves. Among that age group, the rate of H1N1-positive tests was 83% and 82% in the first and second waves, respectively. That compares with rates of 76% and 78%, respectively, in the 5- to 9-year age group. Among adults aged 25–49 years, the rates were 46% and 50%, respectively.

Since the end of the second wave, older children continue to have the highest positivity rates, compared with the other age groups, according to the report. In the 4 weeks ending April 15, 2010, 26% of tests were positive in the 10- to 14-year age group, compared with 18% among younger children and 13% among adults.

When analyzed by geographic region, positivity rates during the same 4-week period were highest (26%) in the southeastern United States (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee). In the central southern states (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), the rate was 22%. Those rates are in contrast to a combined 6% rate in the rest of the country.

The full report is available at www.QuestDiagnostics.com/HealthTrends

The H1N1 virus has “crowded out” other influenza A and B viruses.

Source Courtesy CDC

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Adolescent obesity is associated with midlife nulliparity and nulligravidity even after adjustment for adult weight, amenorrhea, and other reproductive problems according to an analysis of the Study of Women's Health Across the Nation (SWAN).

“While the data are overwhelming that obesity influences fertility, it should be noted that the precise mechanism remains to be elucidated,” emphasized Dr. Alex J. Polotsky of Albert Einstein College of Medicine, New York, and colleagues (Fertil. Steril. 2010;93:2004–11).

Previous studies have shown that adult obesity is associated with anovulation, amenorrhea, and hyperandrogenism—all of which are directly linked to reproductive problems.

However, this study adjusted for adult body mass index (BMI) as well as many explanations for infertility. “Therefore our data point to influences on fertility that are weight-related yet are not necessarily linked with anovulation,” the researchers said.

The study included 3,154 participants in the SWAN study who were aged 42–52 years, had at least one period and no hormone therapy in the prior 3 months, and had an intact uterus and at least one ovary.

Baseline weight and height were measured, and self-reported high school BMI was recorded. Race/ethnicity, education, and marital, smoking, and socioeconomic status were recorded.

The subjects were asked to report the number of times they had been pregnant and the outcome of each pregnancy. The number of induced and spontaneous abortions was recorded as well as any history of infertility, including self-reported use of fertility medications, history of eating disorders, and history of salpingitis. Questions about menstrual regularity and oral contraception were also asked, including details about any history of nongestational amenorrhea. Male factor infertility, decisions to remain childless, and preference for same-sex relationships were also recorded.

A total of 527 (16.7%) of the cohort reported childlessness, and increased high school BMI was associated with higher rates of nulliparity, despite no difference in the rate of induced or spontaneous abortions.

Among women who were underweight in high school (BMI less than 18.5 kg/m

A total of 23% of participants reported a history of a period of infertility, and there were no significant differences in this rate across the weight categories. However, a history of amenorrhea was significantly more common among those with higher high school weights (13.2% and 15.4% in those reporting underweight and normal weight in adolescence, respectively, compared with 21.5% and 30.9% in those reporting overweight and obesity in adolescence).

There was also a higher number of women who never tried to get pregnant in the higher weight categories, and although this was statistically significant (P = .2), the difference was small.

“The findings were not affected by tubal or male factor infertility, use of fertility treatments, decisions to remain voluntarily childless, or preference for same-sex sexual relationship,” wrote the authors. After adjustment for adult BMI, history of amenorrhea, marital status, ethnicity, study site, education, and socioeconomic status, adolescent obesity remained independently associated with lifetime nulliparity and nulligravidity (odds ratios 2.84 an 3.93, respectively), they concluded.

“The cross-sectional nature of our study implies that it should be hypothesis-generating: Does adolescent obesity result in diminished fertility?”

The authors reported having no disclosures. The study was supported by the National Institutes of Health.

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality in the type 1 diabetes group, found in 33.1%.

Data Source: A study of 535 adolescents with type 1 diabetes, who are part of the SEARCH study, and 241 healthy controls.

Disclosures: The SEARCH study is funded by the Centers for Disease Control and Prevention and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declared no conflicts of interest.

Abnormal vascular stiffness, a marker of early vascular disease, is found in adolescents with type 1 diabetes at a rate of about 32% in boys and 6% in girls, according to an analysis of data from the SEARCH for Diabetes in Youth Study.

Type 1 diabetes was an independent predictor of all measures of vascular stiffness, even after adjustment for cardiovascular risk factors, said Dr. Elaine M. Urbina of Cincinnati Children's Hospital Medical Center and her colleagues (J. Pediatr. 2010;156:731–7).

“Patients with [type 1 diabetes], even at a young age, are at an increased risk for vascular stiffness and endothelial function by nature of their disease,” Dr. Janet H. Silverstein, a pediatric endocrinologist at the University of Florida, Gainesville, wrote in an accompanying editorial. “Modifiable risk factors should be monitored and, if they are abnormal, aggressive treatment undertaken.”

The study involved 535 adolescents with type 1 who were part of the larger SEARCH study group; their average age was 14.6 years and 13% were “nonwhite.” The 241 healthy control subjects (average age 17.8 years, 58% “nonwhite”) were selected from an ongoing study of vascular function in adolescents.

Height, weight, body mass index, and waist circumference were recorded for all subjects, as were glycated hemoglobin A_1c, fasting glucose, triglycerides, and total, LDL, and HDL cholesterol.

Vascular function testing included measurement of systolic, diastolic, and mean arterial blood pressure, pulse, heart rate, and brachial artery distensibility (BrachD).

Arterial stiffness was assessed by measurement of pulse wave velocity for the trunk, arm, and leg, plus augmentation index, adjusted to a standard heart rate of 75 beats per minute (AIx-75).

As expected, the study noted higher BP and heart rates, HbA_1c, fasting glucose, and total and LDL cholesterol, and lower HDL cholesterol in the type 1 subjects.

Greater arterial stiffness in the type 1 group was shown in lower BrachD, higher AIx-75, and higher age-adjusted pulse wave velocity trunk measurements.

Decreased BrachD, a measure of peripheral vascular stiffness, was the most common abnormality, in 33.1% of the type 1 patients. Peripheral stiffness correlates with left ventricular hypertrophy and is associated with peripheral artery disease and vessel calcification, the investigators noted. “The independent correlates of vascular dysfunction in this cohort of youth with [type 1 diabetes] included modifiable (higher BP, greater adiposity, and more atherogenic lipid profile) and nonmodifiable CV risk factors (older age, nonwhite race/ethnicity and male sex).”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

Major Finding: More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

Data Source: A cross-sectional study of 710,949 patients aged 2-19 years who were enrolled in an integrated prepaid health plan.

Disclosures: The study was supported by Kaiser Permanente Direct Community Benefit Funds. Dr. Koebnick and her associates declared no conflicts of interest.

Extreme obesity is on the rise in children and adolescents, and certain ethnic/racial minorities face a higher risk than do others, according to a southern Californian study of more than 710,000 subjects.

More than 6% of subjects aged 2-19 years met the criteria for extreme obesity, with the highest rates seen in Hispanic boys aged 6-11 years and 12-19 years (11%), and black girls aged 12-19 years (12%).

“Extreme obesity was observed early in life,” wrote Corinna Koebnick, Ph.D., of Kaiser Permanente Southern California, Pasadena, and her colleagues (J. Pediatr. 2010 March 18 [doi:10.1016/j. jpeds.2010.01.025]).

“Analogous to the concept of 'pack-years' for smoking patients, extremely obese children may suffer cumulative effects of their 'pound-years,'” the authors suggested.

“Without major lifestyle changes, these kids face a 10 to 20 year shorter life span and will develop health problems in their twenties that we typically see in 40- to 60-year-olds,” Dr. Koebnick said in a written statement.

The cross-sectional study included 710,949 patients aged 2-19 years who were enrolled in an integrated, prepaid health plan in 2007 and 2008. All patients had at least one medical office visit during the 2-year study period, and the average number of medical encounters was 2.6 per child per year. Data for body weight and height measurements, which were routinely recorded during such visits, were extracted from a total of 1,849,256 inpatient and outpatient visits.

Weight differences and distribution was assessed across sex- and race/ethnicity–specific categories. Race and ethnicity information was obtained from administrative records and birth certificates, with incomplete information supplemented by data from the U.S. Census Bureau.

Overweight was defined according to Centers for Disease Control growth charts as a body mass index of 25 kg/m

The study found an overall prevalence of overweight, obesity, and extreme obesity in 37.1%, 19.4%, and 6.4% of the subjects, respectively—a combined total of 63% of the study population. Compared with data from 1999 to 2004 from the National Health and Nutrition Examination Survey (NHANES), which found a 3.8% prevalence of extreme obesity, the new findings demonstrate a shift. “Our study does not reflect a right shift of the entire population, but a right shift of obesity towards extreme obesity,” the authors explained.

“Children who are extremely obese are at higher risk of heart disease, type 2 diabetes, fatty liver disease and joint problems, just to name a few,” Dr. Koebnick said in her statement.

However, overall there is relatively limited knowledge about the economic burden and health consequences of extreme childhood obesity, the authors wrote. Given the marked variance in obesity across ethnic/racial groups, “robust and validated risk stratification schemes are needed to address the variability in risks for adverse health outcomes.”

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering

A study of nearly 3,500 patients indicates no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with some caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive.

“We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and his colleagues in the ACCORD Study Group, explaining that the cross-sectional analysis found an adjusted odds ratio (OR) of 0.97 with a wide confidence interval (0.67-1.40), and did not account for duration of thiazolidinedione exposure, past exposure, or type of exposure.

“A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The ACCORD Eye Substudy is the largest study to date to examine the association between diabetic macular edema (DME) and thiazolidinedione, the authors noted (Arch. Ophthalmol. 2010;128:312-8).

The Eye Substudy involved 3,473 participants from the larger ACCORD trial. Subjects were eligible only if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye. Participants had a mean age of 62 years.

DME was scored separately for each eye on a scale of 0 (none) through 3 (retinal thickness or adjacent hard exudates within 500 mcm of the center of the macula). A score of 1 was considered questionable, while 2 was defined as a zone of retinal thickness 1 disk area or greater and within 1 disk diameter or less from the center of the macula. Eyes graded at level 2 or 3 were considered to have clinically significant macular edema.

Thiazolidinedione use was defined as self-reported current use of rosiglitazone or pioglitazone at baseline. The duration of exposure before baseline was not known, however inclusion criteria for the main ACCORD trial required an antihyperglycemic washout period of 3 months before the start of the study.

Among the 3,473 participants, 695 (20%) had used thiazolidinediones, and 217 (6.2%) had DME. In the adjusted analysis, thiazolidinedione use was not significantly associated with DME (OR 0.97), nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between thiazolidinedione and both retinopathy and age.

Former and current smokers had lower prevalence of DME than did those who had never smoked, a finding that “is perhaps attributable to chance or the inclusion process,” wrote the authors, citing a previous study that contradicts this finding (Invest. Ophthalmol. Vis. Sci. 1998;39:233-52).

Thiazolidinedione use was also associated with marginally better visual acuity (P = .009), although “we do not know whether this finding is clinically significant,” they wrote.

The authors pointed out several limitations to the findings, including the possibility that “perhaps longer-term exposure to a thiazolidinedione is necessary for risk to develop.

Disclosures: The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Ambrosius disclosed no conflicts. Among his associates, Dr. Hertzel C. Gerstein has received honoraria and grants from GlaxoSmithKline for speaking, consulting, and research related to thiazolidinediones and/or rosiglitazone. Since 2005, the University of North Carolina, Chapel Hill, has contracted with pharmaceutical companies for Dr. John B. Buse's research or consulting on thiazolidinediones and related compounds. Dr. David C. Goff Jr. has received research funding from Merck and Co. for a trial involving the glucose-lowering medication sitagliptin.

Reflectance map shows edema associated with diabetic retinopathy.

Source Image courtesy Heidelberg Engineering

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

MONTREAL — Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non–insulin-dependent type 2 diabetes patients, based on results from two retrospective studies.

The studies, presented at the annual meeting of the North American Primary Care Research Group, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor for gastroesophageal reflux disease,” he said in an interview. “That was the only change in medication, and the patient's hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch said.

In the first investigation, Dr. Ivan Mefford of Richmond, Tex., studied 347 individuals with type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29–32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not prescribed a PPI (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPIs, compared with 7.3% for those on metformin without PPIs. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPIs had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPIs.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPIs (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” Dr. Crouch said. “He's doing a study now, taking people who don't have GERD and prescribing a PPI to try and improve their diabetes. So far, it's very consistent; they are responding well in about 9 out of 10 cases.”

Disclosures: Dr. Crouch reported that there were no conflicts of interest associated with either study.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

MONTREAL — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over 10 years, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and time of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

The SDI differentiates disease-related vs. treatment-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.”

Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. About 60% flare and require treatment after a median of 3 years. Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients. Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.

A study of nearly 3,500 patients shows no link between thiazolidinedione use and diabetic macular edema, but given case reports of such an association, the findings still must be interpreted with caution, researchers say.

The authors of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial Eye Substudy say the findings are reassuring yet inconclusive. “We cannot rule out the possibility of either a modest protective or deleterious association,” wrote Walter T. Ambrosius, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues in the ACCORD Study Group. “A more definitive answer may be provided from the 4-year follow-up data, which will enable us to examine prospectively the relationship between thiazolidinedione exposure and [diabetic macular edema] incidence.”

The Eye Substudy, which involved 3,473 participants from the ACCORD trial, is the largest study to examine the association between diabetic macular edema and thiazolidinedione (TZD) use, the authors noted. Subjects had a mean age of 62 years and were eligible if they had no previous laser photocoagulation or vitrectomy for diabetic retinopathy in either eye.

A total of 695 subjects (20%) had used TZDs, and 217 (6%) had diabetic macular edema. In the adjusted analysis, TZD use was not significantly associated with diabetic macular edema, nor were hemoglobin A_1c, duration of diabetes, gender, or ethnicity. Significant association was found between TZDs and both retinopathy and age (Arch. Ophthalmol. 2010;128:312–8).

The study was funded by the National Eye Institute and the National Heart, Lung, and Blood Institute. Dr. Gerstein has received honoraria and grants from GlaxoSmithKline. The University of North Carolina, Chapel Hill, has contracted with various pharmaceutical companies for coauthor Dr. John B. Buse's research or consulting on thiazolidinediones. Dr. Goff has received research funding from Merck and Co.