Jeff Evans

NATIONAL HARBOR, MD. — Patients with type 2 diabetes who have undergone laparoscopic Roux-en-Y gastric bypass surgery might experience a significant drop in hemoglobin A_1c levels to below the cutoff value recommended in guidelines, according to a retrospective study.

The procedure maintained its effect through 3 years of follow-up, during which the patients significantly lowered their use of oral hypoglycemic agents and insulin. More than half (53%) of the gastric bypass patients available for follow-up after 3 years experienced remission of their diabetes.

In comparison, an age- and gender-matched cohort of medically managed patients with type 2 diabetes who did not have surgery developed worsening hemoglobin A_1c (HbA_1c) levels and significantly increased use of oral hypoglycemic agents and insulin during a similar time frame.

“We feel that bariatric surgery should be considered a first-line treatment option for obese patients with type 2 diabetes,” Dr. Daniel E. Mumme said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The study that Dr. Mumme, a surgery resident, presented for his colleagues at Gundersen Lutheran Medical Center, La Crosse, Wis., compared the outcomes of 51 patients with type 2 diabetes who underwent laparoscopic Roux-en-Y gastric bypass at the center during 2001-2005 and 51 medically managed patients with type 2 diabetes identified within a family practice database. Patients in both groups had a mean age of 48 years and 78% were female.

In 48 surgical patients with HbA_1c values recorded after 1 year of follow-up, mean HbA_1c levels significantly dropped from 7.5% before surgery to 5.8%. The 29 patients who had 3-year follow-up data experienced a significant drop in mean HbA_1c levels from 7.8% before surgery to 6.1%. HbA_1c levels increased from 7% to 7.8% over a 3-year period in 39 patients of the medically managed comparison cohort. Current treatment guidelines of the American Diabetes Association recommend HbA_1c levels below 7%.

Data from a study investigating the association of HbA_1c with cardiovascular disease and mortality in adults showed that a percentage point increase in HbA_1c was associated with a 20%-30% increase in cardiovascular events or total mortality (Ann. Intern. Med. 2004;141:413-20). In another study, each percentage point drop in HbA_1c was associated with a 37% decline in the risk of microvascular complications (BMJ 2000;321:405-12).

In the current study, the surgical patients lost a mean of 103 pounds, or 68% of their excess weight, at 1 year. The body mass index (BMI) of surgical patients dropped from a mean of 48 kg/m

In surgical patients, the use of oral hypoglycemic agents significantly declined from 77% at baseline to 18% at 1 year and 22% at 3 years. In comparison, oral hypoglycemic use in conventionally treated patients rose from 67% at baseline to 82% at 1 year, remaining stable to 3 years. In both groups, insulin use followed the same trends as oral hypoglycemic agents.

At 3 years, 26% of gastric bypass patients used oral hypoglycemic agents and/or insulin, compared with 82% of conventionally treated patients. Remission of diabetes (defined as an HbA_1c less than 6% and off diabetic medications) occurred at 1 year in 59% of surgical patients and in 35% of conventionally treated patients.

Of the 51 surgical cohort patients, the 31 who had gone into remission during the 3 years of follow-up had had diabetes for a mean of 4.1 years. That was significantly shorter than the mean duration of disease for the 20 patients who never remitted (7.9 years). Overall, surgical patients had a slightly longer mean duration of diabetes than did nonsurgical patients, said Dr. Mumme, who had no disclosures to make for himself or his coinvestigators.

NATIONAL HARBOR, MD. — Patients with type 2 diabetes who have undergone laparoscopic Roux-en-Y gastric bypass surgery might experience a significant drop in hemoglobin A_1c levels to below the cutoff value recommended in guidelines, according to a retrospective study.

The procedure maintained its effect through 3 years of follow-up, during which the patients significantly lowered their use of oral hypoglycemic agents and insulin. More than half (53%) of the gastric bypass patients available for follow-up after 3 years experienced remission of their diabetes.

In comparison, an age- and gender-matched cohort of medically managed patients with type 2 diabetes who did not have surgery developed worsening hemoglobin A_1c (HbA_1c) levels and significantly increased use of oral hypoglycemic agents and insulin during a similar time frame.

“We feel that bariatric surgery should be considered a first-line treatment option for obese patients with type 2 diabetes,” Dr. Daniel E. Mumme said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The study that Dr. Mumme, a surgery resident, presented for his colleagues at Gundersen Lutheran Medical Center, La Crosse, Wis., compared the outcomes of 51 patients with type 2 diabetes who underwent laparoscopic Roux-en-Y gastric bypass at the center during 2001-2005 and 51 medically managed patients with type 2 diabetes identified within a family practice database. Patients in both groups had a mean age of 48 years and 78% were female.

In 48 surgical patients with HbA_1c values recorded after 1 year of follow-up, mean HbA_1c levels significantly dropped from 7.5% before surgery to 5.8%. The 29 patients who had 3-year follow-up data experienced a significant drop in mean HbA_1c levels from 7.8% before surgery to 6.1%. HbA_1c levels increased from 7% to 7.8% over a 3-year period in 39 patients of the medically managed comparison cohort. Current treatment guidelines of the American Diabetes Association recommend HbA_1c levels below 7%.

Data from a study investigating the association of HbA_1c with cardiovascular disease and mortality in adults showed that a percentage point increase in HbA_1c was associated with a 20%-30% increase in cardiovascular events or total mortality (Ann. Intern. Med. 2004;141:413-20). In another study, each percentage point drop in HbA_1c was associated with a 37% decline in the risk of microvascular complications (BMJ 2000;321:405-12).

In the current study, the surgical patients lost a mean of 103 pounds, or 68% of their excess weight, at 1 year. The body mass index (BMI) of surgical patients dropped from a mean of 48 kg/m

In surgical patients, the use of oral hypoglycemic agents significantly declined from 77% at baseline to 18% at 1 year and 22% at 3 years. In comparison, oral hypoglycemic use in conventionally treated patients rose from 67% at baseline to 82% at 1 year, remaining stable to 3 years. In both groups, insulin use followed the same trends as oral hypoglycemic agents.

At 3 years, 26% of gastric bypass patients used oral hypoglycemic agents and/or insulin, compared with 82% of conventionally treated patients. Remission of diabetes (defined as an HbA_1c less than 6% and off diabetic medications) occurred at 1 year in 59% of surgical patients and in 35% of conventionally treated patients.

Of the 51 surgical cohort patients, the 31 who had gone into remission during the 3 years of follow-up had had diabetes for a mean of 4.1 years. That was significantly shorter than the mean duration of disease for the 20 patients who never remitted (7.9 years). Overall, surgical patients had a slightly longer mean duration of diabetes than did nonsurgical patients, said Dr. Mumme, who had no disclosures to make for himself or his coinvestigators.

NATIONAL HARBOR, MD. — Patients with type 2 diabetes who have undergone laparoscopic Roux-en-Y gastric bypass surgery might experience a significant drop in hemoglobin A_1c levels to below the cutoff value recommended in guidelines, according to a retrospective study.

The procedure maintained its effect through 3 years of follow-up, during which the patients significantly lowered their use of oral hypoglycemic agents and insulin. More than half (53%) of the gastric bypass patients available for follow-up after 3 years experienced remission of their diabetes.

In comparison, an age- and gender-matched cohort of medically managed patients with type 2 diabetes who did not have surgery developed worsening hemoglobin A_1c (HbA_1c) levels and significantly increased use of oral hypoglycemic agents and insulin during a similar time frame.

“We feel that bariatric surgery should be considered a first-line treatment option for obese patients with type 2 diabetes,” Dr. Daniel E. Mumme said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

The study that Dr. Mumme, a surgery resident, presented for his colleagues at Gundersen Lutheran Medical Center, La Crosse, Wis., compared the outcomes of 51 patients with type 2 diabetes who underwent laparoscopic Roux-en-Y gastric bypass at the center during 2001-2005 and 51 medically managed patients with type 2 diabetes identified within a family practice database. Patients in both groups had a mean age of 48 years and 78% were female.

In 48 surgical patients with HbA_1c values recorded after 1 year of follow-up, mean HbA_1c levels significantly dropped from 7.5% before surgery to 5.8%. The 29 patients who had 3-year follow-up data experienced a significant drop in mean HbA_1c levels from 7.8% before surgery to 6.1%. HbA_1c levels increased from 7% to 7.8% over a 3-year period in 39 patients of the medically managed comparison cohort. Current treatment guidelines of the American Diabetes Association recommend HbA_1c levels below 7%.

Data from a study investigating the association of HbA_1c with cardiovascular disease and mortality in adults showed that a percentage point increase in HbA_1c was associated with a 20%-30% increase in cardiovascular events or total mortality (Ann. Intern. Med. 2004;141:413-20). In another study, each percentage point drop in HbA_1c was associated with a 37% decline in the risk of microvascular complications (BMJ 2000;321:405-12).

In the current study, the surgical patients lost a mean of 103 pounds, or 68% of their excess weight, at 1 year. The body mass index (BMI) of surgical patients dropped from a mean of 48 kg/m

In surgical patients, the use of oral hypoglycemic agents significantly declined from 77% at baseline to 18% at 1 year and 22% at 3 years. In comparison, oral hypoglycemic use in conventionally treated patients rose from 67% at baseline to 82% at 1 year, remaining stable to 3 years. In both groups, insulin use followed the same trends as oral hypoglycemic agents.

At 3 years, 26% of gastric bypass patients used oral hypoglycemic agents and/or insulin, compared with 82% of conventionally treated patients. Remission of diabetes (defined as an HbA_1c less than 6% and off diabetic medications) occurred at 1 year in 59% of surgical patients and in 35% of conventionally treated patients.

Of the 51 surgical cohort patients, the 31 who had gone into remission during the 3 years of follow-up had had diabetes for a mean of 4.1 years. That was significantly shorter than the mean duration of disease for the 20 patients who never remitted (7.9 years). Overall, surgical patients had a slightly longer mean duration of diabetes than did nonsurgical patients, said Dr. Mumme, who had no disclosures to make for himself or his coinvestigators.

PHILADELPHIA — Laparoscopic adjustable gastric banding in patients with a body mass index less than 35 kg/m

The study is the first to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) in U.S. patients with a BMI less than 35. This BMI value is the cutoff used in National Institutes of Health guidelines on patient selection criteria for weight-loss surgery in people with significant comorbidities, said Dr. Manish Parikh of the general surgery department at New York University.

Of the 53 patients in the study (mean age 47 years), 49 had at least one obesity-related comorbidity, and 44 were women.

The patients' mean preoperative BMI of 33 declined to 28 after 6 months and to 26 after 2 years. The patients lost 48% of their excess weight after 6 months and 70% after 2 years. More than 80% of the patients were available for follow-up at 2 years.

Overall, 75% of the patients had improvement or resolution of their comorbidities, Dr. Parikh reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

The weight loss and improvement in comorbidities seen in the study are important when put into the context of a previous study in which researchers estimated a 25% increase in mortality and 3-4 years of life lost for individuals with a BMI of 25-35—about 20% of U.S. adults, Dr. Parikh said (JAMA 2003;289:187-93).

Previous studies of LAGB in patients with a BMI less than 35 outside the United States have reported similar results. A study of 210 Italian patients reported 72% excess weight loss at 5 years, 89% resolution of comorbidities, an 8% complication rate, and one death 20 months postoperatively due to sepsis stemming from the perforation of a dilated gastric pouch (Obes. Surg. 2004;14:415-8).

A previous study conducted by Dr. Parikh and his associates found that 93 Australian patients lost an average of 54% of their excess weight at 3 years, with improvement or resolution of comorbidities in most (Surg. Obes. Relat. Dis. 2006;2:518-22).

The “most compelling data” for operating on these patients, according to Dr. Parikh, come from a trial in which 80 Australian patients were randomized to undergo LAGB or an intensive nonsurgical weight loss program (Ann. Intern. Med. 2006;144:625-33). The LAGB patients lost a significantly greater percentage of excess weight at 2 years than the nonsurgical group did (87% vs. 22%).

Two of Dr. Parikh's coinvestigators are on the medical advisory board for Allergan Inc., which manufactures the Lap-Band system used in the study.

PHILADELPHIA — Laparoscopic adjustable gastric banding in patients with a body mass index less than 35 kg/m

The study is the first to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) in U.S. patients with a BMI less than 35. This BMI value is the cutoff used in National Institutes of Health guidelines on patient selection criteria for weight-loss surgery in people with significant comorbidities, said Dr. Manish Parikh of the general surgery department at New York University.

Of the 53 patients in the study (mean age 47 years), 49 had at least one obesity-related comorbidity, and 44 were women.

The patients' mean preoperative BMI of 33 declined to 28 after 6 months and to 26 after 2 years. The patients lost 48% of their excess weight after 6 months and 70% after 2 years. More than 80% of the patients were available for follow-up at 2 years.

Overall, 75% of the patients had improvement or resolution of their comorbidities, Dr. Parikh reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

The weight loss and improvement in comorbidities seen in the study are important when put into the context of a previous study in which researchers estimated a 25% increase in mortality and 3-4 years of life lost for individuals with a BMI of 25-35—about 20% of U.S. adults, Dr. Parikh said (JAMA 2003;289:187-93).

Previous studies of LAGB in patients with a BMI less than 35 outside the United States have reported similar results. A study of 210 Italian patients reported 72% excess weight loss at 5 years, 89% resolution of comorbidities, an 8% complication rate, and one death 20 months postoperatively due to sepsis stemming from the perforation of a dilated gastric pouch (Obes. Surg. 2004;14:415-8).

A previous study conducted by Dr. Parikh and his associates found that 93 Australian patients lost an average of 54% of their excess weight at 3 years, with improvement or resolution of comorbidities in most (Surg. Obes. Relat. Dis. 2006;2:518-22).

The “most compelling data” for operating on these patients, according to Dr. Parikh, come from a trial in which 80 Australian patients were randomized to undergo LAGB or an intensive nonsurgical weight loss program (Ann. Intern. Med. 2006;144:625-33). The LAGB patients lost a significantly greater percentage of excess weight at 2 years than the nonsurgical group did (87% vs. 22%).

Two of Dr. Parikh's coinvestigators are on the medical advisory board for Allergan Inc., which manufactures the Lap-Band system used in the study.

PHILADELPHIA — Laparoscopic adjustable gastric banding in patients with a body mass index less than 35 kg/m

The study is the first to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) in U.S. patients with a BMI less than 35. This BMI value is the cutoff used in National Institutes of Health guidelines on patient selection criteria for weight-loss surgery in people with significant comorbidities, said Dr. Manish Parikh of the general surgery department at New York University.

Of the 53 patients in the study (mean age 47 years), 49 had at least one obesity-related comorbidity, and 44 were women.

The patients' mean preoperative BMI of 33 declined to 28 after 6 months and to 26 after 2 years. The patients lost 48% of their excess weight after 6 months and 70% after 2 years. More than 80% of the patients were available for follow-up at 2 years.

Overall, 75% of the patients had improvement or resolution of their comorbidities, Dr. Parikh reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

The weight loss and improvement in comorbidities seen in the study are important when put into the context of a previous study in which researchers estimated a 25% increase in mortality and 3-4 years of life lost for individuals with a BMI of 25-35—about 20% of U.S. adults, Dr. Parikh said (JAMA 2003;289:187-93).

Previous studies of LAGB in patients with a BMI less than 35 outside the United States have reported similar results. A study of 210 Italian patients reported 72% excess weight loss at 5 years, 89% resolution of comorbidities, an 8% complication rate, and one death 20 months postoperatively due to sepsis stemming from the perforation of a dilated gastric pouch (Obes. Surg. 2004;14:415-8).

A previous study conducted by Dr. Parikh and his associates found that 93 Australian patients lost an average of 54% of their excess weight at 3 years, with improvement or resolution of comorbidities in most (Surg. Obes. Relat. Dis. 2006;2:518-22).

The “most compelling data” for operating on these patients, according to Dr. Parikh, come from a trial in which 80 Australian patients were randomized to undergo LAGB or an intensive nonsurgical weight loss program (Ann. Intern. Med. 2006;144:625-33). The LAGB patients lost a significantly greater percentage of excess weight at 2 years than the nonsurgical group did (87% vs. 22%).

Two of Dr. Parikh's coinvestigators are on the medical advisory board for Allergan Inc., which manufactures the Lap-Band system used in the study.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of having developed a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of having developed resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage. Triclosan is known to act on enoyl-acyl carrier protein reductase, called Fab1. Specific mutations in the DNA coding for this protein are known to create cross-resistance to the experimental antibiotic diazaborine and the tuberculosis drug isoniazid, Dr. Aiello said.

Dr. Aiello had no conflicts of interest to disclose.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of having developed a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of having developed resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage. Triclosan is known to act on enoyl-acyl carrier protein reductase, called Fab1. Specific mutations in the DNA coding for this protein are known to create cross-resistance to the experimental antibiotic diazaborine and the tuberculosis drug isoniazid, Dr. Aiello said.

Dr. Aiello had no conflicts of interest to disclose.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of having developed a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of having developed resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage. Triclosan is known to act on enoyl-acyl carrier protein reductase, called Fab1. Specific mutations in the DNA coding for this protein are known to create cross-resistance to the experimental antibiotic diazaborine and the tuberculosis drug isoniazid, Dr. Aiello said.

Dr. Aiello had no conflicts of interest to disclose.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of developing a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of developing resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage.

Dr. Aiello had no conflicts of interest to disclose.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of developing a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of developing resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage.

Dr. Aiello had no conflicts of interest to disclose.

BETHESDA, MD. — Use of household cleaning products that contain benzalkonium chloride may decrease the susceptibility of bacteria to other antimicrobial ingredients in cleaning products and increase their resistance to antibiotics, according to the results of a randomized, double-blind study.

The study is the first randomized intervention study to assess the relationship between the use of two biocidal ingredients found in household cleaning products—benzalkonium chloride (BZK) and triclosan—and antibiotic resistance in the household setting, Allison E. Aiello, Ph.D., reported at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Consumer antiseptics and disinfectants are products that can prevent infections by killing or inhibiting the growth of microorganisms. Biocidal ingredients in these products often are quaternary ammonium compounds (such as BZK) and triclosan.

Some studies have found triclosan in more than 75% of liquid hand-washing soaps sold in the United States. Triclosan has been used ubiquitously since the 1960s and can be found in some toothpaste and embedded in products such as cutting boards and baby diapers. Triclosan also is known to remain in treated sewage that is recycled for use in agriculture, according to Dr. Aiello of the department of epidemiology at the University of Michigan, Ann Arbor.

In 2000, Dr. Aiello and her coinvestigators provided 238 households with either antibacterial products (floor cleaner with 0.08% BZK, surface cleaner with 2.7% BZK, and liquid hand-washing soap with 0.2% triclosan) or the same products without antibacterial ingredients. They cultured the hands of household members before the study started and then after 1 year. Isolates of bacteria from the cultures were tested to determine the minimum inhibitory concentrations (MICs) of BZK and triclosan on which bacteria can grow.

The investigators defined MICs that were above the median for each biocide as “high” and those equal to or less than the median as “low.” The investigators analyzed the general trends and changes over time in all bacterial species combined because they could not compare the same isolates at baseline and at the end of 1 year.

In isolates from all bacterial species combined, there were no differences between the groups in susceptibility to BZK at baseline or 1 year.

Dr. Aiello and her colleagues then analyzed of isolates of bacteria from all species with a high MIC for BZK. At baseline, these isolates from either group of households had similar rates of antibiotic resistance or high MICs for triclosan. But, after 1 year, the isolates that came from households using antibacterial cleaning products had more than twice the odds of developing a high MIC for triclosan than did isolates from households that did not use products with antibacterial ingredients. At 1 year, isolates from households that used antibacterial products also had more than double the likelihood of developing resistance to antibiotics. A subanalysis showed that gram-negative bacterial isolates from households using antibacterial products had nearly fourfold higher odds of developing antibiotic resistance, compared with gram-negative isolates from households that did not use products with antibacterial ingredients.

“Potential selective pressure may result in coselection of resistance genes for other biocides and antibiotics,” Dr. Aiello concluded.

Dr. Aiello and her associates tested all gram-negative bacteria against gentamicin, imipenem, and ciprofloxacin. Certain bacterial species were tested against other types of antibiotics.

No covariates—such as use of a product before enrollment, child day care attendance, or antibiotic use—were associated with susceptibility to BZK or with households that used products containing antibacterial ingredients.

Previous studies have shown that both quaternary ammonium compounds and triclosan can activate efflux pumps in bacteria that transfer plasmids containing resistance genes.

The specific mechanisms of action of quaternary ammonium chlorides are unclear, but they are thought to cause generalized membrane damage.

Dr. Aiello had no conflicts of interest to disclose.

Taking patients with major blunt trauma injury to hospitals that lack a high-level trauma center rather than straight to a level I trauma center may be associated with a higher odds of death, according to findings from a retrospective study.

Although the time interval between injury and reaching definitive care has been positively associated with mortality, no other study has found interhospital transfer to be a predictor of mortality, independent of a delay in care, according to Dr. Raminder Nirula of the department of surgery at the University of Utah, Salt Lake City.

Injured patients often are brought to a nearby facility, but little treatment is done until they are sent elsewhere for a higher level of care, he explained. “Does that pose a risk to the patient, and would it be better to take the patient straight to the higher level of care if it's recognized [by the EMS team] that they're going to need it?” Dr. Nirula said in an interview.

At the core of this question is when and how often it is beneficial to stop at the nearest facility to perform interventions that EMS personnel cannot do. If a lower-level facility is not going to begin definitive treatment, “why stop?” he asked.

Dr. Nirula and his colleagues examined the outcomes of 787 patients who were initially triaged to eight level I trauma centers (including one at the University of Utah Health Sciences Center) and 318 who were initially taken to a nontrauma center and later transferred to one of these level I trauma centers. The patients were part of the Inflammation and Host Response to Injury cohort study, an ongoing multicenter, prospective analysis of the relationship between the inflammatory response to injury and posttraumatic multiple organ failure.

The institutions classified as “nontrauma centers” by the investigators were level II-V trauma centers or community hospitals without a designated trauma center.

Patients who went to a nontrauma center before going to a level I trauma center had about a threefold increase in odds of death, compared with those who were sent directly to a level I trauma center, according to Dr. Nirula, who presented the study at the annual meeting of the American Association for the Surgery of Trauma in Maui, Hawaii.

In multivariate logistic regression analyses, this association remained largely the same regardless of whether clinically relevant factors (trauma center site, significant traumatic brain injury, and receipt of crystalloid or blood transfusion before arrival at a trauma center) were included along with independent predictors of mortality (age, injury severity score, interhospital transfer, time from injury to arrival at the trauma center, and APACHE II score). Exclusion of patients who died within 24 hours did not change the association.

Even though Dr. Nirula and his coinvestigators controlled their analysis for injury severity and physiologic status, no data were available about any interventions performed at the receiving hospital before patient transfer. Such data would help to determine if triage to a nontrauma center were necessary.

A prospective study will help to answer why interhospital transfer is an independent predictor of mortality. It will be important to determine the influence of interventions (or lack thereof) that patients undergo at hospitals before being transferred to a higher-level trauma center, Dr. Nirula said.

The level of EMS training and the type of medical care provided by EMS vary across locations, which may influence transport decisions. Studies of prehospital life support from EMS have reported mixed results on the reduction of mortality. Some studies have shown benefits to advanced trauma life support, whereas others have shown benefits to basic life support alone.

Taking patients with major blunt trauma injury to hospitals that lack a high-level trauma center rather than straight to a level I trauma center may be associated with a higher odds of death, according to findings from a retrospective study.

Although the time interval between injury and reaching definitive care has been positively associated with mortality, no other study has found interhospital transfer to be a predictor of mortality, independent of a delay in care, according to Dr. Raminder Nirula of the department of surgery at the University of Utah, Salt Lake City.

Injured patients often are brought to a nearby facility, but little treatment is done until they are sent elsewhere for a higher level of care, he explained. “Does that pose a risk to the patient, and would it be better to take the patient straight to the higher level of care if it's recognized [by the EMS team] that they're going to need it?” Dr. Nirula said in an interview.

At the core of this question is when and how often it is beneficial to stop at the nearest facility to perform interventions that EMS personnel cannot do. If a lower-level facility is not going to begin definitive treatment, “why stop?” he asked.

Dr. Nirula and his colleagues examined the outcomes of 787 patients who were initially triaged to eight level I trauma centers (including one at the University of Utah Health Sciences Center) and 318 who were initially taken to a nontrauma center and later transferred to one of these level I trauma centers. The patients were part of the Inflammation and Host Response to Injury cohort study, an ongoing multicenter, prospective analysis of the relationship between the inflammatory response to injury and posttraumatic multiple organ failure.

The institutions classified as “nontrauma centers” by the investigators were level II-V trauma centers or community hospitals without a designated trauma center.

Patients who went to a nontrauma center before going to a level I trauma center had about a threefold increase in odds of death, compared with those who were sent directly to a level I trauma center, according to Dr. Nirula, who presented the study at the annual meeting of the American Association for the Surgery of Trauma in Maui, Hawaii.

In multivariate logistic regression analyses, this association remained largely the same regardless of whether clinically relevant factors (trauma center site, significant traumatic brain injury, and receipt of crystalloid or blood transfusion before arrival at a trauma center) were included along with independent predictors of mortality (age, injury severity score, interhospital transfer, time from injury to arrival at the trauma center, and APACHE II score). Exclusion of patients who died within 24 hours did not change the association.

Even though Dr. Nirula and his coinvestigators controlled their analysis for injury severity and physiologic status, no data were available about any interventions performed at the receiving hospital before patient transfer. Such data would help to determine if triage to a nontrauma center were necessary.

A prospective study will help to answer why interhospital transfer is an independent predictor of mortality. It will be important to determine the influence of interventions (or lack thereof) that patients undergo at hospitals before being transferred to a higher-level trauma center, Dr. Nirula said.

The level of EMS training and the type of medical care provided by EMS vary across locations, which may influence transport decisions. Studies of prehospital life support from EMS have reported mixed results on the reduction of mortality. Some studies have shown benefits to advanced trauma life support, whereas others have shown benefits to basic life support alone.

Taking patients with major blunt trauma injury to hospitals that lack a high-level trauma center rather than straight to a level I trauma center may be associated with a higher odds of death, according to findings from a retrospective study.

Although the time interval between injury and reaching definitive care has been positively associated with mortality, no other study has found interhospital transfer to be a predictor of mortality, independent of a delay in care, according to Dr. Raminder Nirula of the department of surgery at the University of Utah, Salt Lake City.

Injured patients often are brought to a nearby facility, but little treatment is done until they are sent elsewhere for a higher level of care, he explained. “Does that pose a risk to the patient, and would it be better to take the patient straight to the higher level of care if it's recognized [by the EMS team] that they're going to need it?” Dr. Nirula said in an interview.

At the core of this question is when and how often it is beneficial to stop at the nearest facility to perform interventions that EMS personnel cannot do. If a lower-level facility is not going to begin definitive treatment, “why stop?” he asked.

Dr. Nirula and his colleagues examined the outcomes of 787 patients who were initially triaged to eight level I trauma centers (including one at the University of Utah Health Sciences Center) and 318 who were initially taken to a nontrauma center and later transferred to one of these level I trauma centers. The patients were part of the Inflammation and Host Response to Injury cohort study, an ongoing multicenter, prospective analysis of the relationship between the inflammatory response to injury and posttraumatic multiple organ failure.

The institutions classified as “nontrauma centers” by the investigators were level II-V trauma centers or community hospitals without a designated trauma center.

Patients who went to a nontrauma center before going to a level I trauma center had about a threefold increase in odds of death, compared with those who were sent directly to a level I trauma center, according to Dr. Nirula, who presented the study at the annual meeting of the American Association for the Surgery of Trauma in Maui, Hawaii.

In multivariate logistic regression analyses, this association remained largely the same regardless of whether clinically relevant factors (trauma center site, significant traumatic brain injury, and receipt of crystalloid or blood transfusion before arrival at a trauma center) were included along with independent predictors of mortality (age, injury severity score, interhospital transfer, time from injury to arrival at the trauma center, and APACHE II score). Exclusion of patients who died within 24 hours did not change the association.

Even though Dr. Nirula and his coinvestigators controlled their analysis for injury severity and physiologic status, no data were available about any interventions performed at the receiving hospital before patient transfer. Such data would help to determine if triage to a nontrauma center were necessary.

A prospective study will help to answer why interhospital transfer is an independent predictor of mortality. It will be important to determine the influence of interventions (or lack thereof) that patients undergo at hospitals before being transferred to a higher-level trauma center, Dr. Nirula said.

The level of EMS training and the type of medical care provided by EMS vary across locations, which may influence transport decisions. Studies of prehospital life support from EMS have reported mixed results on the reduction of mortality. Some studies have shown benefits to advanced trauma life support, whereas others have shown benefits to basic life support alone.

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding, compared with heparin alone, according to a small randomized trial.

This increased rate of bleeding—plus a lack of any added therapeutic benefit with eptifibatide in the trial—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary when a patient has been pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a STEMI (ST-segment elevation myocardial infarction) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many centers in the United States, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% vs. 5.5%, respectively). At 6 months, the similarity between rates persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%).

However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

The trial was performed after the establishment of an integrated, citywide rapid STEMI response system, which helped to achieve a median time from hospital arrival to PCI of 95 minutes in Ottawa.

All of the patients (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

The higher rate of bleeding during eptifibatide treatment—in addition to a lack of an improvement in effectiveness, compared with unfractionated heparin alone—may necessitate another trial in STEMI patients. In this trial, it would make sense to compare unfractionated heparin against bivalirudin (Angiomax) during primary PCI, given that in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, bivalirudin reduced all-cause mortality and rates of major bleeding significantly more than did unfractionated heparin and adjunctive eptifibatide or abciximab, Dr. Le May said.

The ASSIST trial was funded by Schering-Plough Canada Inc. and Medtronic of Canada, although Dr. Le May said that he and his associates initiated the trial independently of industry. Schering-Plough has exclusive U.S. marketing rights to eptifibatide.

Adjunctive eptifibatide led to significantly more major and minor bleeding events combined than did heparin alone. DR. LE MAY

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding, compared with heparin alone, according to a small randomized trial.

This increased rate of bleeding—plus a lack of any added therapeutic benefit with eptifibatide in the trial—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary when a patient has been pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a STEMI (ST-segment elevation myocardial infarction) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many centers in the United States, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% vs. 5.5%, respectively). At 6 months, the similarity between rates persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%).

However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

The trial was performed after the establishment of an integrated, citywide rapid STEMI response system, which helped to achieve a median time from hospital arrival to PCI of 95 minutes in Ottawa.

All of the patients (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

The higher rate of bleeding during eptifibatide treatment—in addition to a lack of an improvement in effectiveness, compared with unfractionated heparin alone—may necessitate another trial in STEMI patients. In this trial, it would make sense to compare unfractionated heparin against bivalirudin (Angiomax) during primary PCI, given that in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, bivalirudin reduced all-cause mortality and rates of major bleeding significantly more than did unfractionated heparin and adjunctive eptifibatide or abciximab, Dr. Le May said.

The ASSIST trial was funded by Schering-Plough Canada Inc. and Medtronic of Canada, although Dr. Le May said that he and his associates initiated the trial independently of industry. Schering-Plough has exclusive U.S. marketing rights to eptifibatide.

Adjunctive eptifibatide led to significantly more major and minor bleeding events combined than did heparin alone. DR. LE MAY

WASHINGTON — The adjunctive use of eptifibatide in antithrombotic regimens that are given to patients undergoing primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction significantly increases the rate of bleeding, compared with heparin alone, according to a small randomized trial.

This increased rate of bleeding—plus a lack of any added therapeutic benefit with eptifibatide in the trial—raises the question of whether treatment with a glycoprotein (GP) IIb/IIIa inhibitor is necessary when a patient has been pretreated for primary PCI with a high loading dose of clopidogrel (Plavix), Dr. Michel R. Le May said at Transcatheter Coronary Therapeutics 2008.

The trial, called ASSIST (A Safety and Efficacy Study of Integrilin-Facilitated PCI in ST Elevation Myocardial Infarction), is the first randomized trial to compare eptifibatide against a control group in the setting of a high (600-mg) loading dose of clopidogrel, said Dr. Le May, director of the Coronary Care Unit Research Group at the University of Ottawa Heart Institute.

Previously, another GP IIb/IIIa inhibitor, abciximab (ReoPro), was shown to have no benefit over unfractionated heparin when patients with a STEMI (ST-segment elevation myocardial infarction) were pretreated with a 600-mg loading dose of clopidogrel before undergoing primary PCI.

Dr. Le May noted that “in many centers in the United States, eptifibatide is now the preferred treatment for primary angioplasty, mostly because it's cheaper. It runs about $800, and abciximab is about twice the price.”

In the open-label trial, 201 patients who took eptifibatide in addition to unfractionated heparin experienced a rate of events in the composite 30-day end point of death, reinfarction, or recurrent severe ischemia that was similar to the rate in patients who received unfractionated heparin alone (6.5% vs. 5.5%, respectively). At 6 months, the similarity between rates persisted (8% and 7.1%, respectively).

Eptifibatide-treated patients experienced significantly more major and minor bleeding events combined in the first 30 days after PCI than did patients who received unfractionated heparin alone (22.4% vs. 14.6%).

However, the differences between the groups in the rates of major bleeding alone or minor bleeding alone did not reach statistical significance, according to the TIMI (Thrombolysis in Myocardial Infarction) score.

The trial was performed after the establishment of an integrated, citywide rapid STEMI response system, which helped to achieve a median time from hospital arrival to PCI of 95 minutes in Ottawa.

All of the patients (mean age, about 60 years) were required to have felt symptoms less than 12 hours before admission. In the unfractionated heparin-only arm of the trial, 3% received eptifibatide and 4% received abciximab as a bail-out treatment.

The higher rate of bleeding during eptifibatide treatment—in addition to a lack of an improvement in effectiveness, compared with unfractionated heparin alone—may necessitate another trial in STEMI patients. In this trial, it would make sense to compare unfractionated heparin against bivalirudin (Angiomax) during primary PCI, given that in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, bivalirudin reduced all-cause mortality and rates of major bleeding significantly more than did unfractionated heparin and adjunctive eptifibatide or abciximab, Dr. Le May said.

The ASSIST trial was funded by Schering-Plough Canada Inc. and Medtronic of Canada, although Dr. Le May said that he and his associates initiated the trial independently of industry. Schering-Plough has exclusive U.S. marketing rights to eptifibatide.

Adjunctive eptifibatide led to significantly more major and minor bleeding events combined than did heparin alone. DR. LE MAY

PHILADELPHIA — Perforated marginal ulcers develop in about 1% of patients who undergo laparoscopic Roux-en-Y gastric bypass, about half of whom may have an etiology associated with smoking at the time of the operation, according to a single-center review of more than 3,400 patients.

Early identification of gastric bypass patients who are at high risk of developing a marginal ulcer would help in initiating measures to prevent ulcer formation or perforation, such as prophylaxis with proton pump inhibitors (PPIs), Dr. Edward L. Felix said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

In a review of a prospectively kept database of 3,430 patients who underwent laparoscopic Roux-en-Y gastric bypass during 1999–2007 at one center, Dr. Felix found that 35 (1%) developed a perforated marginal ulcer (PMU) during a median follow-up of 4 years. These PMUs occurred a median of 18 months (range 3–70 months) after the operation.

Smoking at the time of the bypass was significantly associated with the development of a PMU.

Of the 35 patients with a PMU, 18 were actively smoking at the time of the gastric bypass.

In comparison, out of 100 age-, sex-, and body mass index-matched control patients from Dr. Felix's series who did not have a PMU, only 10 were smokers.

When an audience member asked if he would offer gastric bypass to a patient who was currently smoking, Dr. Felix said yes.

“We try to get them to stop smoking, but I think that is virtually impossible, and I think it's unfair” to deny the operation to the person who smokes and is obese, he said. “I think it's hard enough to get someone to stop eating, let alone stop eating and stop smoking.”

Dr. Felix prescribes PPIs to these patients and warns them that they are at risk of developing an ulcer.

The patients with PMUs had other potential risk factors for an ulcer, including use of nonsteroidal anti-inflammatory drugs (10 cases, 6 of which co-occurred in smokers), previous treatment for a marginal ulcer that had not perforated (4), and use of corticosteroids (2). Some patients had more than one risk factor.

Perforations occurred without any known warning factors or sign in 7 (20%) of the 35 patients with PMUs, comprising only 0.2% of the entire patient series, said Dr. Felix, director of a private bariatric surgery practice in Fresno, Calif.

The investigators tested for Helicobacter pylori infection in five patients with a PMU, but all were negative.

Of the 35 patients with a PMU, 18 were treated at Dr. Felix's center immediately after being diagnosed, 6 were initially seen at an outside hospital and referred to Dr. Felix for treatment, and 11 were seen and treated at an outside hospital.

The PMUs were repaired laparoscopically in 15 cases and as open procedures in 20 cases.

All patients who had a PMU also began taking PPIs after reparative surgery.

After a mean follow-up of 29 months (range 3–62 months), 31 patients had no further perforations, whereas 4 patients (all were current smokers) developed a second PMU. No patients died.

Dr. Felix said that he and his colleagues are now investigating whether keeping all patients who have a marginal ulcer on PPIs for life would decrease the rate of perforation.

Further investigation will be necessary to determine “whether long-term treatment with anything except a proton pump inhibitor will prevent perforation in high-risk patients post bypass,” he added.

Dr. Felix disclosed receiving ownership interest in Pare Surgical Inc. for consulting services, receiving a research grant and financial benefits from W.L. Gore & Associates Inc. for performing contracted research, and receiving financial benefits from Covidien AG.

PHILADELPHIA — Perforated marginal ulcers develop in about 1% of patients who undergo laparoscopic Roux-en-Y gastric bypass, about half of whom may have an etiology associated with smoking at the time of the operation, according to a single-center review of more than 3,400 patients.

Early identification of gastric bypass patients who are at high risk of developing a marginal ulcer would help in initiating measures to prevent ulcer formation or perforation, such as prophylaxis with proton pump inhibitors (PPIs), Dr. Edward L. Felix said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

In a review of a prospectively kept database of 3,430 patients who underwent laparoscopic Roux-en-Y gastric bypass during 1999–2007 at one center, Dr. Felix found that 35 (1%) developed a perforated marginal ulcer (PMU) during a median follow-up of 4 years. These PMUs occurred a median of 18 months (range 3–70 months) after the operation.

Smoking at the time of the bypass was significantly associated with the development of a PMU.

Of the 35 patients with a PMU, 18 were actively smoking at the time of the gastric bypass.

In comparison, out of 100 age-, sex-, and body mass index-matched control patients from Dr. Felix's series who did not have a PMU, only 10 were smokers.

When an audience member asked if he would offer gastric bypass to a patient who was currently smoking, Dr. Felix said yes.

“We try to get them to stop smoking, but I think that is virtually impossible, and I think it's unfair” to deny the operation to the person who smokes and is obese, he said. “I think it's hard enough to get someone to stop eating, let alone stop eating and stop smoking.”

Dr. Felix prescribes PPIs to these patients and warns them that they are at risk of developing an ulcer.

The patients with PMUs had other potential risk factors for an ulcer, including use of nonsteroidal anti-inflammatory drugs (10 cases, 6 of which co-occurred in smokers), previous treatment for a marginal ulcer that had not perforated (4), and use of corticosteroids (2). Some patients had more than one risk factor.

Perforations occurred without any known warning factors or sign in 7 (20%) of the 35 patients with PMUs, comprising only 0.2% of the entire patient series, said Dr. Felix, director of a private bariatric surgery practice in Fresno, Calif.

The investigators tested for Helicobacter pylori infection in five patients with a PMU, but all were negative.

Of the 35 patients with a PMU, 18 were treated at Dr. Felix's center immediately after being diagnosed, 6 were initially seen at an outside hospital and referred to Dr. Felix for treatment, and 11 were seen and treated at an outside hospital.

The PMUs were repaired laparoscopically in 15 cases and as open procedures in 20 cases.

All patients who had a PMU also began taking PPIs after reparative surgery.

After a mean follow-up of 29 months (range 3–62 months), 31 patients had no further perforations, whereas 4 patients (all were current smokers) developed a second PMU. No patients died.

Dr. Felix said that he and his colleagues are now investigating whether keeping all patients who have a marginal ulcer on PPIs for life would decrease the rate of perforation.

Further investigation will be necessary to determine “whether long-term treatment with anything except a proton pump inhibitor will prevent perforation in high-risk patients post bypass,” he added.

Dr. Felix disclosed receiving ownership interest in Pare Surgical Inc. for consulting services, receiving a research grant and financial benefits from W.L. Gore & Associates Inc. for performing contracted research, and receiving financial benefits from Covidien AG.

PHILADELPHIA — Perforated marginal ulcers develop in about 1% of patients who undergo laparoscopic Roux-en-Y gastric bypass, about half of whom may have an etiology associated with smoking at the time of the operation, according to a single-center review of more than 3,400 patients.

Early identification of gastric bypass patients who are at high risk of developing a marginal ulcer would help in initiating measures to prevent ulcer formation or perforation, such as prophylaxis with proton pump inhibitors (PPIs), Dr. Edward L. Felix said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

In a review of a prospectively kept database of 3,430 patients who underwent laparoscopic Roux-en-Y gastric bypass during 1999–2007 at one center, Dr. Felix found that 35 (1%) developed a perforated marginal ulcer (PMU) during a median follow-up of 4 years. These PMUs occurred a median of 18 months (range 3–70 months) after the operation.

Smoking at the time of the bypass was significantly associated with the development of a PMU.

Of the 35 patients with a PMU, 18 were actively smoking at the time of the gastric bypass.

In comparison, out of 100 age-, sex-, and body mass index-matched control patients from Dr. Felix's series who did not have a PMU, only 10 were smokers.

When an audience member asked if he would offer gastric bypass to a patient who was currently smoking, Dr. Felix said yes.

“We try to get them to stop smoking, but I think that is virtually impossible, and I think it's unfair” to deny the operation to the person who smokes and is obese, he said. “I think it's hard enough to get someone to stop eating, let alone stop eating and stop smoking.”

Dr. Felix prescribes PPIs to these patients and warns them that they are at risk of developing an ulcer.

The patients with PMUs had other potential risk factors for an ulcer, including use of nonsteroidal anti-inflammatory drugs (10 cases, 6 of which co-occurred in smokers), previous treatment for a marginal ulcer that had not perforated (4), and use of corticosteroids (2). Some patients had more than one risk factor.

Perforations occurred without any known warning factors or sign in 7 (20%) of the 35 patients with PMUs, comprising only 0.2% of the entire patient series, said Dr. Felix, director of a private bariatric surgery practice in Fresno, Calif.

The investigators tested for Helicobacter pylori infection in five patients with a PMU, but all were negative.

Of the 35 patients with a PMU, 18 were treated at Dr. Felix's center immediately after being diagnosed, 6 were initially seen at an outside hospital and referred to Dr. Felix for treatment, and 11 were seen and treated at an outside hospital.

The PMUs were repaired laparoscopically in 15 cases and as open procedures in 20 cases.

All patients who had a PMU also began taking PPIs after reparative surgery.

After a mean follow-up of 29 months (range 3–62 months), 31 patients had no further perforations, whereas 4 patients (all were current smokers) developed a second PMU. No patients died.

Dr. Felix said that he and his colleagues are now investigating whether keeping all patients who have a marginal ulcer on PPIs for life would decrease the rate of perforation.

Further investigation will be necessary to determine “whether long-term treatment with anything except a proton pump inhibitor will prevent perforation in high-risk patients post bypass,” he added.

Dr. Felix disclosed receiving ownership interest in Pare Surgical Inc. for consulting services, receiving a research grant and financial benefits from W.L. Gore & Associates Inc. for performing contracted research, and receiving financial benefits from Covidien AG.

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial. The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“Tolerability is not affected by doubling the dosage in patients not reaching target levels,” said Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen, the Netherlands.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone, when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment. But solubility drops dramatically with lower temperature, and so lower serum urate values are needed. A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in an interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%). After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial. The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“Tolerability is not affected by doubling the dosage in patients not reaching target levels,” said Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen, the Netherlands.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone, when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment. But solubility drops dramatically with lower temperature, and so lower serum urate values are needed. A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in an interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%). After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial. The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“Tolerability is not affected by doubling the dosage in patients not reaching target levels,” said Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen, the Netherlands.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone, when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment. But solubility drops dramatically with lower temperature, and so lower serum urate values are needed. A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in an interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%). After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

NEW ORLEANS — People who experience routine episodes of dozing during the daytime may have a higher risk of stroke and other vascular events, according to a prospective, community-based cohort study of more than 2,000 people.

The risk of stroke also appeared to increase as the frequency of daytime dozing rose, suggesting a dose-response effect, Bernadette Boden-Albala, Dr.P.H., reported at the International Stroke Conference 2008.

To investigate the relationship between daytime sleepiness (as a measure of underlying sleep disturbance) and stroke, Dr. Boden-Albala and her associates used data from the multiethnic Northern Manhattan Study of 3,298 residents living in that part of the island. The study has been ongoing since 1993 and stopped enrollment in 2002, but the Epworth Sleepiness Scale (ESS) and other questions about sleep and sleep disorders were not collected until nearly 2004, said Dr. Boden-Albala of the departments of neurology and sociomedical sciences at Columbia University, New York.

A total of 2,092 participants answered questions relating to sleep disturbance for the study. These people had an average age of 73 years and a high school graduation rate of 45%. The study comprised 18% whites, 20% blacks, and 60% Hispanics (2% were other ethnicities).

The investigators asked all of the participants the following questions:

▸ Do you know or have you been told that you snore at night?

▸ Do you know or have you been told that you choke or stop breathing when you are sleeping and, if yes, does it occur less than 5 nights per week (mild to moderate) or more than 5 nights per week (severe)?

Some degree of snoring was reported by 63%, whereas only 6% reported choking or stopping breathing during sleep.

Each participant also answered eight questions on a modified version of the ESS, which asked about daytime sleepiness to document sleep disturbance. The scale asks, “How often would you say that you doze while: you're sitting and reading; watching television; sitting inactive in a public place; as a passenger in a car, train, or bus; sitting or talking to someone; sitting quietly after lunch; as a driver in a car; or in any other situation where you doze,” Dr. Boden-Albala said at the conference, which was sponsored by the American Stroke Association.

Overall, 44% reported no dozing, 47% reported some dozing, and 9% reported a significant level of dozing, defined on the ESS as a score of 10 or higher.

During a mean follow-up period of 2.3 years, the participants have suffered 40 strokes (31 of which were ischemic), 123 vascular events (stroke, myocardial infarction, or vascular death), and 156 total deaths.

There was no significant association between snoring (at any level of severity) and vascular events, but there was a significant dose-response relationship between a person's level of sleepiness and their risk for stroke. Patients who reported some dozing had more than twice the risk of both ischemic stroke and all types of stroke, compared with people who reported no dozing, whereas those with “significant dozing” had a more than threefold higher risk of ischemic stroke and a more than fourfold higher risk of all types of stroke. These analyses were adjusted for age, gender, race/ethnicity, education, systolic blood pressure, diabetes, physical activity, obesity, and coronary artery disease.

Compared with participants who reported no dozing, the risk of having a vascular event was 40% higher for those who reported some dozing and was more than two times higher for those who reported significant dozing.

The study is limited by an uncertainty of what truly is being measured. Is it measuring sleep apnea, disturbance, or deprivation, she asked, or is there an underlying process that is contributing to daytime sleepiness?

“We need to validate all of this with gold-standard sleep studies, although the Epworth [Sleepiness] Scale has been tested and has been well validated,” Dr. Boden-Albala cautioned.

“The elevated risk in the highly prevalent 'some dozing' group [shows that] the impact of this novel risk factor may be quite important in further studies,” she concluded.

Prior to the current study, most studies in this area of research have focused on the associations between sleep (apnea and deprivation) and the development of vascular risk factors such as hypertension, obesity, and diabetes, as well as the relationship between sleep apnea and stroke.

NEW ORLEANS — People who experience routine episodes of dozing during the daytime may have a higher risk of stroke and other vascular events, according to a prospective, community-based cohort study of more than 2,000 people.

The risk of stroke also appeared to increase as the frequency of daytime dozing rose, suggesting a dose-response effect, Bernadette Boden-Albala, Dr.P.H., reported at the International Stroke Conference 2008.

To investigate the relationship between daytime sleepiness (as a measure of underlying sleep disturbance) and stroke, Dr. Boden-Albala and her associates used data from the multiethnic Northern Manhattan Study of 3,298 residents living in that part of the island. The study has been ongoing since 1993 and stopped enrollment in 2002, but the Epworth Sleepiness Scale (ESS) and other questions about sleep and sleep disorders were not collected until nearly 2004, said Dr. Boden-Albala of the departments of neurology and sociomedical sciences at Columbia University, New York.

A total of 2,092 participants answered questions relating to sleep disturbance for the study. These people had an average age of 73 years and a high school graduation rate of 45%. The study comprised 18% whites, 20% blacks, and 60% Hispanics (2% were other ethnicities).

The investigators asked all of the participants the following questions:

▸ Do you know or have you been told that you snore at night?

▸ Do you know or have you been told that you choke or stop breathing when you are sleeping and, if yes, does it occur less than 5 nights per week (mild to moderate) or more than 5 nights per week (severe)?

Some degree of snoring was reported by 63%, whereas only 6% reported choking or stopping breathing during sleep.

Each participant also answered eight questions on a modified version of the ESS, which asked about daytime sleepiness to document sleep disturbance. The scale asks, “How often would you say that you doze while: you're sitting and reading; watching television; sitting inactive in a public place; as a passenger in a car, train, or bus; sitting or talking to someone; sitting quietly after lunch; as a driver in a car; or in any other situation where you doze,” Dr. Boden-Albala said at the conference, which was sponsored by the American Stroke Association.

Overall, 44% reported no dozing, 47% reported some dozing, and 9% reported a significant level of dozing, defined on the ESS as a score of 10 or higher.

During a mean follow-up period of 2.3 years, the participants have suffered 40 strokes (31 of which were ischemic), 123 vascular events (stroke, myocardial infarction, or vascular death), and 156 total deaths.

There was no significant association between snoring (at any level of severity) and vascular events, but there was a significant dose-response relationship between a person's level of sleepiness and their risk for stroke. Patients who reported some dozing had more than twice the risk of both ischemic stroke and all types of stroke, compared with people who reported no dozing, whereas those with “significant dozing” had a more than threefold higher risk of ischemic stroke and a more than fourfold higher risk of all types of stroke. These analyses were adjusted for age, gender, race/ethnicity, education, systolic blood pressure, diabetes, physical activity, obesity, and coronary artery disease.

Compared with participants who reported no dozing, the risk of having a vascular event was 40% higher for those who reported some dozing and was more than two times higher for those who reported significant dozing.

The study is limited by an uncertainty of what truly is being measured. Is it measuring sleep apnea, disturbance, or deprivation, she asked, or is there an underlying process that is contributing to daytime sleepiness?

“We need to validate all of this with gold-standard sleep studies, although the Epworth [Sleepiness] Scale has been tested and has been well validated,” Dr. Boden-Albala cautioned.

“The elevated risk in the highly prevalent 'some dozing' group [shows that] the impact of this novel risk factor may be quite important in further studies,” she concluded.

Prior to the current study, most studies in this area of research have focused on the associations between sleep (apnea and deprivation) and the development of vascular risk factors such as hypertension, obesity, and diabetes, as well as the relationship between sleep apnea and stroke.

NEW ORLEANS — People who experience routine episodes of dozing during the daytime may have a higher risk of stroke and other vascular events, according to a prospective, community-based cohort study of more than 2,000 people.

The risk of stroke also appeared to increase as the frequency of daytime dozing rose, suggesting a dose-response effect, Bernadette Boden-Albala, Dr.P.H., reported at the International Stroke Conference 2008.

To investigate the relationship between daytime sleepiness (as a measure of underlying sleep disturbance) and stroke, Dr. Boden-Albala and her associates used data from the multiethnic Northern Manhattan Study of 3,298 residents living in that part of the island. The study has been ongoing since 1993 and stopped enrollment in 2002, but the Epworth Sleepiness Scale (ESS) and other questions about sleep and sleep disorders were not collected until nearly 2004, said Dr. Boden-Albala of the departments of neurology and sociomedical sciences at Columbia University, New York.

A total of 2,092 participants answered questions relating to sleep disturbance for the study. These people had an average age of 73 years and a high school graduation rate of 45%. The study comprised 18% whites, 20% blacks, and 60% Hispanics (2% were other ethnicities).

The investigators asked all of the participants the following questions:

▸ Do you know or have you been told that you snore at night?

▸ Do you know or have you been told that you choke or stop breathing when you are sleeping and, if yes, does it occur less than 5 nights per week (mild to moderate) or more than 5 nights per week (severe)?

Some degree of snoring was reported by 63%, whereas only 6% reported choking or stopping breathing during sleep.

Each participant also answered eight questions on a modified version of the ESS, which asked about daytime sleepiness to document sleep disturbance. The scale asks, “How often would you say that you doze while: you're sitting and reading; watching television; sitting inactive in a public place; as a passenger in a car, train, or bus; sitting or talking to someone; sitting quietly after lunch; as a driver in a car; or in any other situation where you doze,” Dr. Boden-Albala said at the conference, which was sponsored by the American Stroke Association.

Overall, 44% reported no dozing, 47% reported some dozing, and 9% reported a significant level of dozing, defined on the ESS as a score of 10 or higher.

During a mean follow-up period of 2.3 years, the participants have suffered 40 strokes (31 of which were ischemic), 123 vascular events (stroke, myocardial infarction, or vascular death), and 156 total deaths.

There was no significant association between snoring (at any level of severity) and vascular events, but there was a significant dose-response relationship between a person's level of sleepiness and their risk for stroke. Patients who reported some dozing had more than twice the risk of both ischemic stroke and all types of stroke, compared with people who reported no dozing, whereas those with “significant dozing” had a more than threefold higher risk of ischemic stroke and a more than fourfold higher risk of all types of stroke. These analyses were adjusted for age, gender, race/ethnicity, education, systolic blood pressure, diabetes, physical activity, obesity, and coronary artery disease.

Compared with participants who reported no dozing, the risk of having a vascular event was 40% higher for those who reported some dozing and was more than two times higher for those who reported significant dozing.

The study is limited by an uncertainty of what truly is being measured. Is it measuring sleep apnea, disturbance, or deprivation, she asked, or is there an underlying process that is contributing to daytime sleepiness?

“We need to validate all of this with gold-standard sleep studies, although the Epworth [Sleepiness] Scale has been tested and has been well validated,” Dr. Boden-Albala cautioned.

“The elevated risk in the highly prevalent 'some dozing' group [shows that] the impact of this novel risk factor may be quite important in further studies,” she concluded.

Prior to the current study, most studies in this area of research have focused on the associations between sleep (apnea and deprivation) and the development of vascular risk factors such as hypertension, obesity, and diabetes, as well as the relationship between sleep apnea and stroke.

KISSIMMEE, FLA. — Dermal and epidermal pigmentary disorders in East Asian patients can be treated successfully in many cases without causing postinflammatory hyperpigmentation by carefully combining topical bleaching agents with either a Q-switched laser or intense pulsed light.

Careful attention to the device settings as well as the patient's skin type and any presence of melasma will help to ensure the best results with a low risk of postinflammatory hyperpigmentation (PIH), said Dr. Kei Negishi of Tokyo Women's Medical University.

To remove epidermal pigmentation that commonly occurs in East Asians, such as solar lentigines, freckles, melasma, PIH, and pigmented seborrheic keratoses, Dr. Negishi advised using a Q-switched laser, intense pulsed light (set to specific lesion parameters or full-face), and/or topical bleaching cream. Her patients are mainly Japanese, but she also sees some South Korean and Chinese patients.

If the treatment is for a small number of epidermal pigmentary lesions, she recommended using a Q-switched laser or intense pulsed light (IPL) set to a specific lesion parameter, combined with a topical bleaching cream such as hydroquinone or retinoic acid.

Q-switched lasers are the only devices that are capable of removing dermal pigment, such as nevus of Ota or acquired dermal melanocytosis, without scarring. Long-pulsed lasers and IPL would cause permanent scarring, Dr. Negishi said at the annual meeting of the American Society for Laser Medicine and Surgery.

Avoiding PIH

PIH has been reported to occur 1 month after treatment for solar lentigines with a Q-switched laser in 10%-25% of Chinese patients and 43%-44% of Japanese patients. In Dr. Negishi's own studies, she has found that the addition of a bleaching cream (composed of hydroquinone and retinoic acid) to Q-switched laser treatment plus a steroid and antibiotics could reduce the incidence of PIH by 20%-40%. There was a higher risk of PIH in her patients with skin types IV and V, and in those with melasma, she reported.

To minimize the incidence of PIH, Dr. Negishi suggested using minimum fluences within the window of efficacy for each device, and testing the laser in an inconspicuous area on a patient when it will be used for large or multiple areas. Posttreatment cooling, immediately after treatment, also sometimes helps, she said.

In patients at high risk for PIH, she advises using bleaching agents 2-4 weeks before Q-switched laser treatment, followed by steroid treatment for 7 days after treatment, and then an additional 3-4 weeks of bleaching cream. She also advises patients to use sunscreen every day during the treatment period.

To treat PIH with obvious erythema, she recommended using a steroid plus a mild bleaching agent, such as vitamin C derivatives. In cases without erythema, treatment with IPL at a mild setting can shorten the recovery period, in addition to 2% or 5% hydroquinone, 0.025% or 0.05% retinoic acid, and 0.025% dexamethasone, if it is tolerable.

IPL for Epidermal Pigmentation

The main advantage of using IPL to treat epidermal pigmentation is its reduced risk of causing PIH, Dr. Negishi said. IPL does not disrupt melanosomes, unlike Q-switched lasers, but instead affects melanin-rich keratinocytes, inducing the formation of a microcrust and a partial turnover of the epidermis. Multiple IPL treatments might be necessary to treat pigmentation, and IPLs with a shorter wavelength range have greater efficacy.

Dr. Negishi reported that after an IPL treatment, reflectance-mode confocal microscopy reveals the rapid migration of melanocytes to the basal layer. This suggests that in order to stimulate IPL's efficacy, patients should begin using bleaching cream immediately after the microcrust peels off, she said. With "Q-switched lasers, bleaching creams are used to prevent PIH, but with IPL, they are used to stimulate treatment efficacy," she said.

IPL also is a good choice for full-face skin rejuvenation and whitening in East Asians, Dr. Negishi said.

For each IPL treatment, Dr. Negishi first checks the patient for melasma and acquired dermal melanocytosis. She uses the UV light in a Wood's lamp to distinguish acquired dermal melanocytosis from subtle or hidden melasma rather than just to determine the area of melasma. She then uses a spectrophotometer to check the patient's skin color.

She uses a mild parameter setting for full-face irradiation, consisting of longer wavelengths at low fluences. For specific lesions, she increases the fluence, shortens the pulse width, or shortens the wavelength, using white paper to cover the area surrounding the lesion. The immediate reaction to full-face IPL should be very slight erythema in normally pigmented areas and a slight darkening of pigmented areas with pain remaining about 3-4 on a 10-point scale.

Particular attention should be paid when using IPL for full facial skin rejuvenation in patients with darker skin, such as those with type V skin or type IV plus sun damage, because of the risk of epidermal burning. For patients with darker skin or melasma, it is preferable to use a long wavelength/low fluence setting for second passes over specific lesions with white paper covering the surrounding area, she said.

In a study, Dr. Negishi and her coinvestigators used an ultraviolet filter to identify very subtle epidermal melasma in 63 (28%) of 223 East Asian patients who had previously not been diagnosed with melasma. The patients who did not use sunscreen had a significantly higher risk of the condition than those who did use it (Dermatol. Surg. 2004;30:881-6). "This type of pigmentation tends to worsen with aggressive IPL treatment," she said.

Melasma in East Asians is thought to be epidermal, caused by an increased number of melanocytes and increased activity of melanogenic enzymes, which leaves the skin at a high risk for PIH.

IPL treatment alone is not enough to remove melasma, so Dr. Negishi commonly uses topical agents (such as 2%-5% hydroquinone, 5%-10% vitamin C derivative, or 0.025%-0.4% tretinoin) or oral tranexamic acid as her first choice to use in combination with IPL.

Oral tranexamic acid has been used for treating melasma in East Asians for more than 20 years, according to Dr. Negishi. When telangiectasias are present concurrently with melasma, she uses a long-pulse 1,064-nm Nd:YAG laser to reduce the vascular lesions while also stimulating epidermal turnover.

Dr. Negishi reported that she conducted much of her research with equipment borrowed from Cutera Inc., Danish Dermatologic Development A/S, Lumenis Ltd., and Syneron Inc., but she has no financial interests with any of these companies.

KISSIMMEE, FLA. — Dermal and epidermal pigmentary disorders in East Asian patients can be treated successfully in many cases without causing postinflammatory hyperpigmentation by carefully combining topical bleaching agents with either a Q-switched laser or intense pulsed light.

Careful attention to the device settings as well as the patient's skin type and any presence of melasma will help to ensure the best results with a low risk of postinflammatory hyperpigmentation (PIH), said Dr. Kei Negishi of Tokyo Women's Medical University.

To remove epidermal pigmentation that commonly occurs in East Asians, such as solar lentigines, freckles, melasma, PIH, and pigmented seborrheic keratoses, Dr. Negishi advised using a Q-switched laser, intense pulsed light (set to specific lesion parameters or full-face), and/or topical bleaching cream. Her patients are mainly Japanese, but she also sees some South Korean and Chinese patients.

If the treatment is for a small number of epidermal pigmentary lesions, she recommended using a Q-switched laser or intense pulsed light (IPL) set to a specific lesion parameter, combined with a topical bleaching cream such as hydroquinone or retinoic acid.

Q-switched lasers are the only devices that are capable of removing dermal pigment, such as nevus of Ota or acquired dermal melanocytosis, without scarring. Long-pulsed lasers and IPL would cause permanent scarring, Dr. Negishi said at the annual meeting of the American Society for Laser Medicine and Surgery.

Avoiding PIH

PIH has been reported to occur 1 month after treatment for solar lentigines with a Q-switched laser in 10%-25% of Chinese patients and 43%-44% of Japanese patients. In Dr. Negishi's own studies, she has found that the addition of a bleaching cream (composed of hydroquinone and retinoic acid) to Q-switched laser treatment plus a steroid and antibiotics could reduce the incidence of PIH by 20%-40%. There was a higher risk of PIH in her patients with skin types IV and V, and in those with melasma, she reported.

To minimize the incidence of PIH, Dr. Negishi suggested using minimum fluences within the window of efficacy for each device, and testing the laser in an inconspicuous area on a patient when it will be used for large or multiple areas. Posttreatment cooling, immediately after treatment, also sometimes helps, she said.

In patients at high risk for PIH, she advises using bleaching agents 2-4 weeks before Q-switched laser treatment, followed by steroid treatment for 7 days after treatment, and then an additional 3-4 weeks of bleaching cream. She also advises patients to use sunscreen every day during the treatment period.

To treat PIH with obvious erythema, she recommended using a steroid plus a mild bleaching agent, such as vitamin C derivatives. In cases without erythema, treatment with IPL at a mild setting can shorten the recovery period, in addition to 2% or 5% hydroquinone, 0.025% or 0.05% retinoic acid, and 0.025% dexamethasone, if it is tolerable.

IPL for Epidermal Pigmentation

The main advantage of using IPL to treat epidermal pigmentation is its reduced risk of causing PIH, Dr. Negishi said. IPL does not disrupt melanosomes, unlike Q-switched lasers, but instead affects melanin-rich keratinocytes, inducing the formation of a microcrust and a partial turnover of the epidermis. Multiple IPL treatments might be necessary to treat pigmentation, and IPLs with a shorter wavelength range have greater efficacy.

Dr. Negishi reported that after an IPL treatment, reflectance-mode confocal microscopy reveals the rapid migration of melanocytes to the basal layer. This suggests that in order to stimulate IPL's efficacy, patients should begin using bleaching cream immediately after the microcrust peels off, she said. With "Q-switched lasers, bleaching creams are used to prevent PIH, but with IPL, they are used to stimulate treatment efficacy," she said.

IPL also is a good choice for full-face skin rejuvenation and whitening in East Asians, Dr. Negishi said.

For each IPL treatment, Dr. Negishi first checks the patient for melasma and acquired dermal melanocytosis. She uses the UV light in a Wood's lamp to distinguish acquired dermal melanocytosis from subtle or hidden melasma rather than just to determine the area of melasma. She then uses a spectrophotometer to check the patient's skin color.

She uses a mild parameter setting for full-face irradiation, consisting of longer wavelengths at low fluences. For specific lesions, she increases the fluence, shortens the pulse width, or shortens the wavelength, using white paper to cover the area surrounding the lesion. The immediate reaction to full-face IPL should be very slight erythema in normally pigmented areas and a slight darkening of pigmented areas with pain remaining about 3-4 on a 10-point scale.

Particular attention should be paid when using IPL for full facial skin rejuvenation in patients with darker skin, such as those with type V skin or type IV plus sun damage, because of the risk of epidermal burning. For patients with darker skin or melasma, it is preferable to use a long wavelength/low fluence setting for second passes over specific lesions with white paper covering the surrounding area, she said.

In a study, Dr. Negishi and her coinvestigators used an ultraviolet filter to identify very subtle epidermal melasma in 63 (28%) of 223 East Asian patients who had previously not been diagnosed with melasma. The patients who did not use sunscreen had a significantly higher risk of the condition than those who did use it (Dermatol. Surg. 2004;30:881-6). "This type of pigmentation tends to worsen with aggressive IPL treatment," she said.

Melasma in East Asians is thought to be epidermal, caused by an increased number of melanocytes and increased activity of melanogenic enzymes, which leaves the skin at a high risk for PIH.

IPL treatment alone is not enough to remove melasma, so Dr. Negishi commonly uses topical agents (such as 2%-5% hydroquinone, 5%-10% vitamin C derivative, or 0.025%-0.4% tretinoin) or oral tranexamic acid as her first choice to use in combination with IPL.

Oral tranexamic acid has been used for treating melasma in East Asians for more than 20 years, according to Dr. Negishi. When telangiectasias are present concurrently with melasma, she uses a long-pulse 1,064-nm Nd:YAG laser to reduce the vascular lesions while also stimulating epidermal turnover.

Dr. Negishi reported that she conducted much of her research with equipment borrowed from Cutera Inc., Danish Dermatologic Development A/S, Lumenis Ltd., and Syneron Inc., but she has no financial interests with any of these companies.

KISSIMMEE, FLA. — Dermal and epidermal pigmentary disorders in East Asian patients can be treated successfully in many cases without causing postinflammatory hyperpigmentation by carefully combining topical bleaching agents with either a Q-switched laser or intense pulsed light.

Careful attention to the device settings as well as the patient's skin type and any presence of melasma will help to ensure the best results with a low risk of postinflammatory hyperpigmentation (PIH), said Dr. Kei Negishi of Tokyo Women's Medical University.

To remove epidermal pigmentation that commonly occurs in East Asians, such as solar lentigines, freckles, melasma, PIH, and pigmented seborrheic keratoses, Dr. Negishi advised using a Q-switched laser, intense pulsed light (set to specific lesion parameters or full-face), and/or topical bleaching cream. Her patients are mainly Japanese, but she also sees some South Korean and Chinese patients.

If the treatment is for a small number of epidermal pigmentary lesions, she recommended using a Q-switched laser or intense pulsed light (IPL) set to a specific lesion parameter, combined with a topical bleaching cream such as hydroquinone or retinoic acid.

Q-switched lasers are the only devices that are capable of removing dermal pigment, such as nevus of Ota or acquired dermal melanocytosis, without scarring. Long-pulsed lasers and IPL would cause permanent scarring, Dr. Negishi said at the annual meeting of the American Society for Laser Medicine and Surgery.

Avoiding PIH

PIH has been reported to occur 1 month after treatment for solar lentigines with a Q-switched laser in 10%-25% of Chinese patients and 43%-44% of Japanese patients. In Dr. Negishi's own studies, she has found that the addition of a bleaching cream (composed of hydroquinone and retinoic acid) to Q-switched laser treatment plus a steroid and antibiotics could reduce the incidence of PIH by 20%-40%. There was a higher risk of PIH in her patients with skin types IV and V, and in those with melasma, she reported.

To minimize the incidence of PIH, Dr. Negishi suggested using minimum fluences within the window of efficacy for each device, and testing the laser in an inconspicuous area on a patient when it will be used for large or multiple areas. Posttreatment cooling, immediately after treatment, also sometimes helps, she said.

In patients at high risk for PIH, she advises using bleaching agents 2-4 weeks before Q-switched laser treatment, followed by steroid treatment for 7 days after treatment, and then an additional 3-4 weeks of bleaching cream. She also advises patients to use sunscreen every day during the treatment period.

To treat PIH with obvious erythema, she recommended using a steroid plus a mild bleaching agent, such as vitamin C derivatives. In cases without erythema, treatment with IPL at a mild setting can shorten the recovery period, in addition to 2% or 5% hydroquinone, 0.025% or 0.05% retinoic acid, and 0.025% dexamethasone, if it is tolerable.

IPL for Epidermal Pigmentation

The main advantage of using IPL to treat epidermal pigmentation is its reduced risk of causing PIH, Dr. Negishi said. IPL does not disrupt melanosomes, unlike Q-switched lasers, but instead affects melanin-rich keratinocytes, inducing the formation of a microcrust and a partial turnover of the epidermis. Multiple IPL treatments might be necessary to treat pigmentation, and IPLs with a shorter wavelength range have greater efficacy.

Dr. Negishi reported that after an IPL treatment, reflectance-mode confocal microscopy reveals the rapid migration of melanocytes to the basal layer. This suggests that in order to stimulate IPL's efficacy, patients should begin using bleaching cream immediately after the microcrust peels off, she said. With "Q-switched lasers, bleaching creams are used to prevent PIH, but with IPL, they are used to stimulate treatment efficacy," she said.

IPL also is a good choice for full-face skin rejuvenation and whitening in East Asians, Dr. Negishi said.

For each IPL treatment, Dr. Negishi first checks the patient for melasma and acquired dermal melanocytosis. She uses the UV light in a Wood's lamp to distinguish acquired dermal melanocytosis from subtle or hidden melasma rather than just to determine the area of melasma. She then uses a spectrophotometer to check the patient's skin color.

She uses a mild parameter setting for full-face irradiation, consisting of longer wavelengths at low fluences. For specific lesions, she increases the fluence, shortens the pulse width, or shortens the wavelength, using white paper to cover the area surrounding the lesion. The immediate reaction to full-face IPL should be very slight erythema in normally pigmented areas and a slight darkening of pigmented areas with pain remaining about 3-4 on a 10-point scale.

Particular attention should be paid when using IPL for full facial skin rejuvenation in patients with darker skin, such as those with type V skin or type IV plus sun damage, because of the risk of epidermal burning. For patients with darker skin or melasma, it is preferable to use a long wavelength/low fluence setting for second passes over specific lesions with white paper covering the surrounding area, she said.

In a study, Dr. Negishi and her coinvestigators used an ultraviolet filter to identify very subtle epidermal melasma in 63 (28%) of 223 East Asian patients who had previously not been diagnosed with melasma. The patients who did not use sunscreen had a significantly higher risk of the condition than those who did use it (Dermatol. Surg. 2004;30:881-6). "This type of pigmentation tends to worsen with aggressive IPL treatment," she said.

Melasma in East Asians is thought to be epidermal, caused by an increased number of melanocytes and increased activity of melanogenic enzymes, which leaves the skin at a high risk for PIH.

IPL treatment alone is not enough to remove melasma, so Dr. Negishi commonly uses topical agents (such as 2%-5% hydroquinone, 5%-10% vitamin C derivative, or 0.025%-0.4% tretinoin) or oral tranexamic acid as her first choice to use in combination with IPL.

Oral tranexamic acid has been used for treating melasma in East Asians for more than 20 years, according to Dr. Negishi. When telangiectasias are present concurrently with melasma, she uses a long-pulse 1,064-nm Nd:YAG laser to reduce the vascular lesions while also stimulating epidermal turnover.

Dr. Negishi reported that she conducted much of her research with equipment borrowed from Cutera Inc., Danish Dermatologic Development A/S, Lumenis Ltd., and Syneron Inc., but she has no financial interests with any of these companies.