Patrice Wendling

CHICAGO — Obesity was not a risk factor for postoperative mortality or major complications in patients undergoing major intra-abdominal cancer surgery, according to data from a prospective, multicenter risk-adjusted cohort study of 2,258 patients.

As observed in previous studies, however, obesity was a risk factor for minor complications, primarily wound infections.

Importantly, patients who were underweight had a fivefold increased risk of postoperative death, perhaps as a consequence of their underlying poor nutritional status or impaired immunity, investigator Dr. John T. Mullen reported at a symposium sponsored by the Society of Surgical Oncology.

“The prejudice that overweight and obese patients are at increased risk for serious adverse outcomes after major cancer surgery is not justified,” he said. “Paradoxically, overweight status and mild obesity status may be protective of low mortality.”

This possible “obesity paradox” warrants further study, whereas underweight patients might benefit from perioperative nutritional supplementation to mitigate their increased risk of mortality, Dr. Mullen, a surgical oncologist at Beth Israel Deaconess Medical Center, Boston, and his associates concluded.

Underweight patients in the study were significantly more likely to have lost more than 10% of their body weight in the 6 months prior to surgery and to have a lower mean preoperative serum albumin level than other patients have.

Using National Institutes of Health-defined body mass index (BMI) classes, 55 patients were stratified as underweight (BMI up to 18.5 kg/m

Patients underwent the following surgeries from October 2001 to September 2004 at hospitals participating in the Patient Safety in Surgery Study of the National Surgical Quality Improvement Program: 29 esophagectomy, 223 gastrectomy, 554 hepatectomy, 699 pancreatectomy, and 753 low anterior resection/proctectomy.

The risk of postoperative death was greatest at the extremes of BMI class, with a 30-day mortality rate of 9% among underweight patients, 2% among normal weight, 2.1% among overweight, 0.84% among obese I, 0.73% among obese II, and 3.8% among obese III, Dr. Mullen said.

In a multivariate analysis that examined 97 variables, the risk of postoperative death was significantly higher for underweight patients, with an odds ratio of 5.24, compared with patients stratified as normal (OR 1.00), overweight (OR 1.06), obese I (OR 0.61), obese II (OR 0.45), and obese III (OR 1.67).

The 30-day morbidity rate was 22% (OR 0.94), 23% (OR 1.00), 26% (OR 1.22), 29% (OR 1.42), 30% (OR 1.42), and 33% (OR 1.50), respectively, Dr. Mullen said.

There was a progressive and significant increase in minor complications, which included only urinary tract and wound infections, with increasing BMI class: underweight 9%, normal weight 13%, overweight 14%, obese I 17%, obese II 18%, and obese III 25%, said Dr. Mullen, who received no funding for the study and reported no conflicts of interest.

There were no differences among the BMI classes in total operative time or number of patients returning to the operating room.

Obesity has long been considered a potential risk factor for poor surgical outcomes, yet the published data are conflicting, Dr. Mullen said. The few studies that have examined outcomes after major cancer surgery have shown only an increased incidence of intra-abdominal and superficial wound infections. They were limited, however, by small numbers, retrospective design, limited patient follow-up, heterogeneity, and types of procedures studied, he said.

CHICAGO — Obesity was not a risk factor for postoperative mortality or major complications in patients undergoing major intra-abdominal cancer surgery, according to data from a prospective, multicenter risk-adjusted cohort study of 2,258 patients.

As observed in previous studies, however, obesity was a risk factor for minor complications, primarily wound infections.

Importantly, patients who were underweight had a fivefold increased risk of postoperative death, perhaps as a consequence of their underlying poor nutritional status or impaired immunity, investigator Dr. John T. Mullen reported at a symposium sponsored by the Society of Surgical Oncology.

“The prejudice that overweight and obese patients are at increased risk for serious adverse outcomes after major cancer surgery is not justified,” he said. “Paradoxically, overweight status and mild obesity status may be protective of low mortality.”

This possible “obesity paradox” warrants further study, whereas underweight patients might benefit from perioperative nutritional supplementation to mitigate their increased risk of mortality, Dr. Mullen, a surgical oncologist at Beth Israel Deaconess Medical Center, Boston, and his associates concluded.

Underweight patients in the study were significantly more likely to have lost more than 10% of their body weight in the 6 months prior to surgery and to have a lower mean preoperative serum albumin level than other patients have.

Using National Institutes of Health-defined body mass index (BMI) classes, 55 patients were stratified as underweight (BMI up to 18.5 kg/m

Patients underwent the following surgeries from October 2001 to September 2004 at hospitals participating in the Patient Safety in Surgery Study of the National Surgical Quality Improvement Program: 29 esophagectomy, 223 gastrectomy, 554 hepatectomy, 699 pancreatectomy, and 753 low anterior resection/proctectomy.

The risk of postoperative death was greatest at the extremes of BMI class, with a 30-day mortality rate of 9% among underweight patients, 2% among normal weight, 2.1% among overweight, 0.84% among obese I, 0.73% among obese II, and 3.8% among obese III, Dr. Mullen said.

In a multivariate analysis that examined 97 variables, the risk of postoperative death was significantly higher for underweight patients, with an odds ratio of 5.24, compared with patients stratified as normal (OR 1.00), overweight (OR 1.06), obese I (OR 0.61), obese II (OR 0.45), and obese III (OR 1.67).

The 30-day morbidity rate was 22% (OR 0.94), 23% (OR 1.00), 26% (OR 1.22), 29% (OR 1.42), 30% (OR 1.42), and 33% (OR 1.50), respectively, Dr. Mullen said.

There was a progressive and significant increase in minor complications, which included only urinary tract and wound infections, with increasing BMI class: underweight 9%, normal weight 13%, overweight 14%, obese I 17%, obese II 18%, and obese III 25%, said Dr. Mullen, who received no funding for the study and reported no conflicts of interest.

There were no differences among the BMI classes in total operative time or number of patients returning to the operating room.

Obesity has long been considered a potential risk factor for poor surgical outcomes, yet the published data are conflicting, Dr. Mullen said. The few studies that have examined outcomes after major cancer surgery have shown only an increased incidence of intra-abdominal and superficial wound infections. They were limited, however, by small numbers, retrospective design, limited patient follow-up, heterogeneity, and types of procedures studied, he said.

CHICAGO — Obesity was not a risk factor for postoperative mortality or major complications in patients undergoing major intra-abdominal cancer surgery, according to data from a prospective, multicenter risk-adjusted cohort study of 2,258 patients.

As observed in previous studies, however, obesity was a risk factor for minor complications, primarily wound infections.

Importantly, patients who were underweight had a fivefold increased risk of postoperative death, perhaps as a consequence of their underlying poor nutritional status or impaired immunity, investigator Dr. John T. Mullen reported at a symposium sponsored by the Society of Surgical Oncology.

“The prejudice that overweight and obese patients are at increased risk for serious adverse outcomes after major cancer surgery is not justified,” he said. “Paradoxically, overweight status and mild obesity status may be protective of low mortality.”

This possible “obesity paradox” warrants further study, whereas underweight patients might benefit from perioperative nutritional supplementation to mitigate their increased risk of mortality, Dr. Mullen, a surgical oncologist at Beth Israel Deaconess Medical Center, Boston, and his associates concluded.

Underweight patients in the study were significantly more likely to have lost more than 10% of their body weight in the 6 months prior to surgery and to have a lower mean preoperative serum albumin level than other patients have.

Using National Institutes of Health-defined body mass index (BMI) classes, 55 patients were stratified as underweight (BMI up to 18.5 kg/m

Patients underwent the following surgeries from October 2001 to September 2004 at hospitals participating in the Patient Safety in Surgery Study of the National Surgical Quality Improvement Program: 29 esophagectomy, 223 gastrectomy, 554 hepatectomy, 699 pancreatectomy, and 753 low anterior resection/proctectomy.

The risk of postoperative death was greatest at the extremes of BMI class, with a 30-day mortality rate of 9% among underweight patients, 2% among normal weight, 2.1% among overweight, 0.84% among obese I, 0.73% among obese II, and 3.8% among obese III, Dr. Mullen said.

In a multivariate analysis that examined 97 variables, the risk of postoperative death was significantly higher for underweight patients, with an odds ratio of 5.24, compared with patients stratified as normal (OR 1.00), overweight (OR 1.06), obese I (OR 0.61), obese II (OR 0.45), and obese III (OR 1.67).

The 30-day morbidity rate was 22% (OR 0.94), 23% (OR 1.00), 26% (OR 1.22), 29% (OR 1.42), 30% (OR 1.42), and 33% (OR 1.50), respectively, Dr. Mullen said.

There was a progressive and significant increase in minor complications, which included only urinary tract and wound infections, with increasing BMI class: underweight 9%, normal weight 13%, overweight 14%, obese I 17%, obese II 18%, and obese III 25%, said Dr. Mullen, who received no funding for the study and reported no conflicts of interest.

There were no differences among the BMI classes in total operative time or number of patients returning to the operating room.

Obesity has long been considered a potential risk factor for poor surgical outcomes, yet the published data are conflicting, Dr. Mullen said. The few studies that have examined outcomes after major cancer surgery have shown only an increased incidence of intra-abdominal and superficial wound infections. They were limited, however, by small numbers, retrospective design, limited patient follow-up, heterogeneity, and types of procedures studied, he said.

CHICAGO — The use of dexamethasone therapy either before or with the first dose of standard antibiotics was associated with a favorable outcome in adults with community-acquired bacterial meningitis, according to preliminary data from a prospective nationwide cohort of 154 Dutch patients.

Adjunctive dexamethasone has been recommended as routine therapy for adults with suspected or proven pneumococcal meningitis in recent practice management guidelines in the Netherlands and by the Infectious Diseases Society of America (Clin. Infect. Dis. 2004;39:1267–84). In making its recommendation concerning adults, the society cited a randomized trial, conducted by the same study group, demonstrating that adjunctive dexamethasone reduces both unfavorable outcomes and mortality in adults with bacterial meningitis (N. Engl. J. Med. 2002;347:1549–56).

The current study identified 215 patients aged at least 17 years who had a positive cerebrospinal fluid culture for community-acquired bacterial meningitis from March 2006 to April 2007, Dr. Matthijs C. Brouwer reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Complete data were available on 154 of the patients. In all, 106 were infected with Streptococcus pneumoniae (69%), 26 with Neisseria meningitidis (17%), and 22 with other bacteria (14%), said Dr. Brouwer of the Academic Medical Center of the University of Amsterdam. Upon admission, patients' median age was 60 years (range 43–69 years), 87 were male, 29 had a Glasgow Coma Scale score lower than 8, and 39 (25%) had neurologic deficits.

The use of dexamethasone therapy was recorded in 151 (98%) of the patients. Of these, 121 received 10 mg four times daily for 4 days before or with antibiotics, 13 received other dexamethasone regimens that continued for as long as 10 days in some cases, and 17 did not receive dexamethasone.

Of the 154 patients, 31 died; 47 had an unfavorable outcome as defined by a Glasgow Outcome Scale score of 4 or lower; 22 suffered sequelae defined as neurologic deficits and cranial nerve palsy including hearing loss; and 104 had a favorable outcome. (Some patients were assigned to more than one category.)

Of those with pneumococcal meningitis, 25 died and 37 experienced unfavorable outcomes. None of the patients with meningococcal meningitis died, but two had unfavorable outcomes. Of those with meningitis resulting from other bacteria, six died and eight had unfavorable outcomes.

Compared with all cases of bacterial meningitis in the cohort, mortality and unfavorable outcomes were slightly higher for pneumococcal meningitis, which is more severe than other types. However, the rates were lower than those reported by the study group for pneumococcal meningitis in its earlier (1998–2002) cohort.

“We believe the decrease in mortality in pneumococcal meningitis (from 30% to 24%) and unfavorable outcome (from 50% to 35%) was due to the introduction of dexamethasone,” Dr. Brouwer said in an interview.

In a multivariate analysis, significant risk factors for an unfavorable outcome were age older than 60 years (odds ratio 5.79), a white blood cell count lower than 1,000 cells/mL of cerebral spinal fluid (OR 7.75), a Glasgow Coma Scale score lower than 8 (OR 3.09), and a heart rate greater than 120 beats per minute (OR 10.1).

Standard dexamethasone therapy was a significant protective factor against unfavorable outcome, with an odds ratio of 0.21 and a P value of .004. When the causative bacterium was added to the model, the effect of dexamethasone remained unchanged, Dr. Brouwer said at the meeting, which was sponsored by the American Society for Microbiology.

The researchers also found that the incidence of meningococcal meningitis in the Netherlands has fallen to less than 20% from 37% during 1998–2002.

CHICAGO — The use of dexamethasone therapy either before or with the first dose of standard antibiotics was associated with a favorable outcome in adults with community-acquired bacterial meningitis, according to preliminary data from a prospective nationwide cohort of 154 Dutch patients.

Adjunctive dexamethasone has been recommended as routine therapy for adults with suspected or proven pneumococcal meningitis in recent practice management guidelines in the Netherlands and by the Infectious Diseases Society of America (Clin. Infect. Dis. 2004;39:1267–84). In making its recommendation concerning adults, the society cited a randomized trial, conducted by the same study group, demonstrating that adjunctive dexamethasone reduces both unfavorable outcomes and mortality in adults with bacterial meningitis (N. Engl. J. Med. 2002;347:1549–56).

The current study identified 215 patients aged at least 17 years who had a positive cerebrospinal fluid culture for community-acquired bacterial meningitis from March 2006 to April 2007, Dr. Matthijs C. Brouwer reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Complete data were available on 154 of the patients. In all, 106 were infected with Streptococcus pneumoniae (69%), 26 with Neisseria meningitidis (17%), and 22 with other bacteria (14%), said Dr. Brouwer of the Academic Medical Center of the University of Amsterdam. Upon admission, patients' median age was 60 years (range 43–69 years), 87 were male, 29 had a Glasgow Coma Scale score lower than 8, and 39 (25%) had neurologic deficits.

The use of dexamethasone therapy was recorded in 151 (98%) of the patients. Of these, 121 received 10 mg four times daily for 4 days before or with antibiotics, 13 received other dexamethasone regimens that continued for as long as 10 days in some cases, and 17 did not receive dexamethasone.

Of the 154 patients, 31 died; 47 had an unfavorable outcome as defined by a Glasgow Outcome Scale score of 4 or lower; 22 suffered sequelae defined as neurologic deficits and cranial nerve palsy including hearing loss; and 104 had a favorable outcome. (Some patients were assigned to more than one category.)

Of those with pneumococcal meningitis, 25 died and 37 experienced unfavorable outcomes. None of the patients with meningococcal meningitis died, but two had unfavorable outcomes. Of those with meningitis resulting from other bacteria, six died and eight had unfavorable outcomes.

Compared with all cases of bacterial meningitis in the cohort, mortality and unfavorable outcomes were slightly higher for pneumococcal meningitis, which is more severe than other types. However, the rates were lower than those reported by the study group for pneumococcal meningitis in its earlier (1998–2002) cohort.

“We believe the decrease in mortality in pneumococcal meningitis (from 30% to 24%) and unfavorable outcome (from 50% to 35%) was due to the introduction of dexamethasone,” Dr. Brouwer said in an interview.

In a multivariate analysis, significant risk factors for an unfavorable outcome were age older than 60 years (odds ratio 5.79), a white blood cell count lower than 1,000 cells/mL of cerebral spinal fluid (OR 7.75), a Glasgow Coma Scale score lower than 8 (OR 3.09), and a heart rate greater than 120 beats per minute (OR 10.1).

Standard dexamethasone therapy was a significant protective factor against unfavorable outcome, with an odds ratio of 0.21 and a P value of .004. When the causative bacterium was added to the model, the effect of dexamethasone remained unchanged, Dr. Brouwer said at the meeting, which was sponsored by the American Society for Microbiology.

The researchers also found that the incidence of meningococcal meningitis in the Netherlands has fallen to less than 20% from 37% during 1998–2002.

CHICAGO — The use of dexamethasone therapy either before or with the first dose of standard antibiotics was associated with a favorable outcome in adults with community-acquired bacterial meningitis, according to preliminary data from a prospective nationwide cohort of 154 Dutch patients.

Adjunctive dexamethasone has been recommended as routine therapy for adults with suspected or proven pneumococcal meningitis in recent practice management guidelines in the Netherlands and by the Infectious Diseases Society of America (Clin. Infect. Dis. 2004;39:1267–84). In making its recommendation concerning adults, the society cited a randomized trial, conducted by the same study group, demonstrating that adjunctive dexamethasone reduces both unfavorable outcomes and mortality in adults with bacterial meningitis (N. Engl. J. Med. 2002;347:1549–56).

The current study identified 215 patients aged at least 17 years who had a positive cerebrospinal fluid culture for community-acquired bacterial meningitis from March 2006 to April 2007, Dr. Matthijs C. Brouwer reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Complete data were available on 154 of the patients. In all, 106 were infected with Streptococcus pneumoniae (69%), 26 with Neisseria meningitidis (17%), and 22 with other bacteria (14%), said Dr. Brouwer of the Academic Medical Center of the University of Amsterdam. Upon admission, patients' median age was 60 years (range 43–69 years), 87 were male, 29 had a Glasgow Coma Scale score lower than 8, and 39 (25%) had neurologic deficits.

The use of dexamethasone therapy was recorded in 151 (98%) of the patients. Of these, 121 received 10 mg four times daily for 4 days before or with antibiotics, 13 received other dexamethasone regimens that continued for as long as 10 days in some cases, and 17 did not receive dexamethasone.

Of the 154 patients, 31 died; 47 had an unfavorable outcome as defined by a Glasgow Outcome Scale score of 4 or lower; 22 suffered sequelae defined as neurologic deficits and cranial nerve palsy including hearing loss; and 104 had a favorable outcome. (Some patients were assigned to more than one category.)

Of those with pneumococcal meningitis, 25 died and 37 experienced unfavorable outcomes. None of the patients with meningococcal meningitis died, but two had unfavorable outcomes. Of those with meningitis resulting from other bacteria, six died and eight had unfavorable outcomes.

Compared with all cases of bacterial meningitis in the cohort, mortality and unfavorable outcomes were slightly higher for pneumococcal meningitis, which is more severe than other types. However, the rates were lower than those reported by the study group for pneumococcal meningitis in its earlier (1998–2002) cohort.

“We believe the decrease in mortality in pneumococcal meningitis (from 30% to 24%) and unfavorable outcome (from 50% to 35%) was due to the introduction of dexamethasone,” Dr. Brouwer said in an interview.

In a multivariate analysis, significant risk factors for an unfavorable outcome were age older than 60 years (odds ratio 5.79), a white blood cell count lower than 1,000 cells/mL of cerebral spinal fluid (OR 7.75), a Glasgow Coma Scale score lower than 8 (OR 3.09), and a heart rate greater than 120 beats per minute (OR 10.1).

Standard dexamethasone therapy was a significant protective factor against unfavorable outcome, with an odds ratio of 0.21 and a P value of .004. When the causative bacterium was added to the model, the effect of dexamethasone remained unchanged, Dr. Brouwer said at the meeting, which was sponsored by the American Society for Microbiology.

The researchers also found that the incidence of meningococcal meningitis in the Netherlands has fallen to less than 20% from 37% during 1998–2002.

CHICAGO — A topical ointment containing components derived from green tea leaves is the latest addition to the available therapies for genital warts, Dr. Thomas C. Wright Jr. said at a conference on vulvovaginal diseases.

The ointment was approved by the Food and Drug Administration in October 2006, based on pooled results of two randomized, double-blind phase III trials in patients who used the ointment three times daily for up to 16 weeks. Complete clearance was reported in 213 of 397 patients (54%) treated with Veregen, compared with 73 of 207 (35%) patients on placebo. Higher clearance rates were reported in Veregen-treated women (60%) than in men (47%).

Veregen Ointment 15% is a botanical drug product that is specifically indicated for the topical treatment of external genital and perianal warts in immunocompetent patients aged 18 years and older. It is expected to be available in the United States by prescription only, said Dr. Wright, professor of pathology, director of gynecologic and obstetric pathology, Columbia University, New York.

The drug substance in Veregen Ointment is sinecatechins, which is a partially purified fraction of the water extract of green tea leaves from Camellia sinensis (L.) O. Kuntze, and is a mixture of catechins and other green tea components. Catechins are thought to enhance immune system function and are more abundant in green tea leaves than in black tea leaves.

However, of the 397 patients who were treated with Veregen, 12 (30%) reported a severe local reaction that probably was related to the drug, Dr. Wright said. The incidence of local adverse events leading to discontinuation or dose reduction was 5% (19 patients). The most common adverse events were erythema, pruritus, burning, pain or discomfort, and erosion or ulceration.

Veregen Ointment 15% has not been tested in immunosuppressed patients or in nursing mothers and is an FDA pregnancy category C drug, Dr. Wright said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology.

The ointment was developed by MediGene AG, a biotech company based in Martinsried, Germany, and it will be distributed in the United States by Doak Dermatologics.

MediGene has agreed to a phase IV trial, comparing the pharmacokinetics of catechins following topical administration of Veregen ointment 15% with that after oral administration of a green tea solution. The trial is expected to start in January 2008 and will include 40 patients with external genital and perianal warts.

Other new treatments for external genital warts include Histofreezer (OraSure Technologies Inc.), a prepackaged portable cryosurgery unit that consists of a handheld canister of cryogen and a variety of applicators. The product is indicated for use on nine different types of lesions, including external genital warts. Histofreezer costs about $4 per use and is easier to use than large cryosurgery tanks, Dr. Wright said, adding that he has not used the product.

It produces a level of freezing (−55° C) similar to that achieved with carbon dioxide or nitrous oxide cryotherapy and therefore should perform similarly, he said. Reported clearance rates are similar to those in the literature for other forms of cryotherapy.

Local ablative methods such as cryotherapy, fulguration, and trichloroacetic acid are best if there are just a few lesions, whereas if there are more lesions, it is better to treat them with self-applied modalities such as imiquimod, Dr. Wright said.

Lasers also are useful but should be reserved for patients who fail chemical or immune modulation therapy. Lasers often are required in immunocompromised patients and those with large amounts of disease, he said.

Dr. Wright disclosed no financial or advisory relationships with MediGene AG, Doak Dermatologics, or OraSure Technologies.

CHICAGO — A topical ointment containing components derived from green tea leaves is the latest addition to the available therapies for genital warts, Dr. Thomas C. Wright Jr. said at a conference on vulvovaginal diseases.

The ointment was approved by the Food and Drug Administration in October 2006, based on pooled results of two randomized, double-blind phase III trials in patients who used the ointment three times daily for up to 16 weeks. Complete clearance was reported in 213 of 397 patients (54%) treated with Veregen, compared with 73 of 207 (35%) patients on placebo. Higher clearance rates were reported in Veregen-treated women (60%) than in men (47%).

Veregen Ointment 15% is a botanical drug product that is specifically indicated for the topical treatment of external genital and perianal warts in immunocompetent patients aged 18 years and older. It is expected to be available in the United States by prescription only, said Dr. Wright, professor of pathology, director of gynecologic and obstetric pathology, Columbia University, New York.

The drug substance in Veregen Ointment is sinecatechins, which is a partially purified fraction of the water extract of green tea leaves from Camellia sinensis (L.) O. Kuntze, and is a mixture of catechins and other green tea components. Catechins are thought to enhance immune system function and are more abundant in green tea leaves than in black tea leaves.

However, of the 397 patients who were treated with Veregen, 12 (30%) reported a severe local reaction that probably was related to the drug, Dr. Wright said. The incidence of local adverse events leading to discontinuation or dose reduction was 5% (19 patients). The most common adverse events were erythema, pruritus, burning, pain or discomfort, and erosion or ulceration.

Veregen Ointment 15% has not been tested in immunosuppressed patients or in nursing mothers and is an FDA pregnancy category C drug, Dr. Wright said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology.

The ointment was developed by MediGene AG, a biotech company based in Martinsried, Germany, and it will be distributed in the United States by Doak Dermatologics.

MediGene has agreed to a phase IV trial, comparing the pharmacokinetics of catechins following topical administration of Veregen ointment 15% with that after oral administration of a green tea solution. The trial is expected to start in January 2008 and will include 40 patients with external genital and perianal warts.

Other new treatments for external genital warts include Histofreezer (OraSure Technologies Inc.), a prepackaged portable cryosurgery unit that consists of a handheld canister of cryogen and a variety of applicators. The product is indicated for use on nine different types of lesions, including external genital warts. Histofreezer costs about $4 per use and is easier to use than large cryosurgery tanks, Dr. Wright said, adding that he has not used the product.

It produces a level of freezing (−55° C) similar to that achieved with carbon dioxide or nitrous oxide cryotherapy and therefore should perform similarly, he said. Reported clearance rates are similar to those in the literature for other forms of cryotherapy.

Local ablative methods such as cryotherapy, fulguration, and trichloroacetic acid are best if there are just a few lesions, whereas if there are more lesions, it is better to treat them with self-applied modalities such as imiquimod, Dr. Wright said.

Lasers also are useful but should be reserved for patients who fail chemical or immune modulation therapy. Lasers often are required in immunocompromised patients and those with large amounts of disease, he said.

Dr. Wright disclosed no financial or advisory relationships with MediGene AG, Doak Dermatologics, or OraSure Technologies.

CHICAGO — A topical ointment containing components derived from green tea leaves is the latest addition to the available therapies for genital warts, Dr. Thomas C. Wright Jr. said at a conference on vulvovaginal diseases.

The ointment was approved by the Food and Drug Administration in October 2006, based on pooled results of two randomized, double-blind phase III trials in patients who used the ointment three times daily for up to 16 weeks. Complete clearance was reported in 213 of 397 patients (54%) treated with Veregen, compared with 73 of 207 (35%) patients on placebo. Higher clearance rates were reported in Veregen-treated women (60%) than in men (47%).

Veregen Ointment 15% is a botanical drug product that is specifically indicated for the topical treatment of external genital and perianal warts in immunocompetent patients aged 18 years and older. It is expected to be available in the United States by prescription only, said Dr. Wright, professor of pathology, director of gynecologic and obstetric pathology, Columbia University, New York.

The drug substance in Veregen Ointment is sinecatechins, which is a partially purified fraction of the water extract of green tea leaves from Camellia sinensis (L.) O. Kuntze, and is a mixture of catechins and other green tea components. Catechins are thought to enhance immune system function and are more abundant in green tea leaves than in black tea leaves.

However, of the 397 patients who were treated with Veregen, 12 (30%) reported a severe local reaction that probably was related to the drug, Dr. Wright said. The incidence of local adverse events leading to discontinuation or dose reduction was 5% (19 patients). The most common adverse events were erythema, pruritus, burning, pain or discomfort, and erosion or ulceration.

Veregen Ointment 15% has not been tested in immunosuppressed patients or in nursing mothers and is an FDA pregnancy category C drug, Dr. Wright said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology.

The ointment was developed by MediGene AG, a biotech company based in Martinsried, Germany, and it will be distributed in the United States by Doak Dermatologics.

MediGene has agreed to a phase IV trial, comparing the pharmacokinetics of catechins following topical administration of Veregen ointment 15% with that after oral administration of a green tea solution. The trial is expected to start in January 2008 and will include 40 patients with external genital and perianal warts.

Other new treatments for external genital warts include Histofreezer (OraSure Technologies Inc.), a prepackaged portable cryosurgery unit that consists of a handheld canister of cryogen and a variety of applicators. The product is indicated for use on nine different types of lesions, including external genital warts. Histofreezer costs about $4 per use and is easier to use than large cryosurgery tanks, Dr. Wright said, adding that he has not used the product.

It produces a level of freezing (−55° C) similar to that achieved with carbon dioxide or nitrous oxide cryotherapy and therefore should perform similarly, he said. Reported clearance rates are similar to those in the literature for other forms of cryotherapy.

Local ablative methods such as cryotherapy, fulguration, and trichloroacetic acid are best if there are just a few lesions, whereas if there are more lesions, it is better to treat them with self-applied modalities such as imiquimod, Dr. Wright said.

Lasers also are useful but should be reserved for patients who fail chemical or immune modulation therapy. Lasers often are required in immunocompromised patients and those with large amounts of disease, he said.

Dr. Wright disclosed no financial or advisory relationships with MediGene AG, Doak Dermatologics, or OraSure Technologies.

CHICAGO — Contrary to some reports, oseltamivir therapy appears not to affect the incidence of neuropsychiatric events in patients with influenza, according to data presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The study used a large U.S. medical claims database to compare the incidence of neuropsychiatric events in the 30 days after an influenza diagnosis in patients who received oseltamivir versus those given no antiviral treatment.

Recent case reports from a variety of countries have linked oseltamivir to neuropsychiatric events. Although no causality has been established, the product label has been changed to include neuropsychiatric events in the European Union, Japan, Switzerland, and the United States, reported lead investigator Marsha A. Wilcox, Sc.D., and colleagues at i3 Drug Safety, in Waltham, Mass.

From Nov. 1, 1999, through April 30, 2005, 60,267 patients were treated with oseltamivir and 175,933 received no antivirals. The two cohorts were balanced for a variety of baseline variables including age, sex, health plan region, index date, number of hospitalizations, and vaccinations for influenza and pneumococcus during the 6 months prior to diagnosis.

The incidence of any neuropsychiatric event was 3.8% in the oseltamivir group and 4.3% in those not treated with antivirals (exposure-adjusted odds ratio 0.89).

The incidence was also comparable for major neuropsychiatric events (3.4% vs. 3.7%; OR 0.89) and for central nervous system stimulation events (2.5% vs. 2.8%; OR 0.88), the investigators reported.

The conference was sponsored by the American Society for Microbiology.

Dr. Wilcox did not disclose any relevant conflicts of interest.

CHICAGO — Contrary to some reports, oseltamivir therapy appears not to affect the incidence of neuropsychiatric events in patients with influenza, according to data presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The study used a large U.S. medical claims database to compare the incidence of neuropsychiatric events in the 30 days after an influenza diagnosis in patients who received oseltamivir versus those given no antiviral treatment.

Recent case reports from a variety of countries have linked oseltamivir to neuropsychiatric events. Although no causality has been established, the product label has been changed to include neuropsychiatric events in the European Union, Japan, Switzerland, and the United States, reported lead investigator Marsha A. Wilcox, Sc.D., and colleagues at i3 Drug Safety, in Waltham, Mass.

From Nov. 1, 1999, through April 30, 2005, 60,267 patients were treated with oseltamivir and 175,933 received no antivirals. The two cohorts were balanced for a variety of baseline variables including age, sex, health plan region, index date, number of hospitalizations, and vaccinations for influenza and pneumococcus during the 6 months prior to diagnosis.

The incidence of any neuropsychiatric event was 3.8% in the oseltamivir group and 4.3% in those not treated with antivirals (exposure-adjusted odds ratio 0.89).

The incidence was also comparable for major neuropsychiatric events (3.4% vs. 3.7%; OR 0.89) and for central nervous system stimulation events (2.5% vs. 2.8%; OR 0.88), the investigators reported.

The conference was sponsored by the American Society for Microbiology.

Dr. Wilcox did not disclose any relevant conflicts of interest.

CHICAGO — Contrary to some reports, oseltamivir therapy appears not to affect the incidence of neuropsychiatric events in patients with influenza, according to data presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The study used a large U.S. medical claims database to compare the incidence of neuropsychiatric events in the 30 days after an influenza diagnosis in patients who received oseltamivir versus those given no antiviral treatment.

Recent case reports from a variety of countries have linked oseltamivir to neuropsychiatric events. Although no causality has been established, the product label has been changed to include neuropsychiatric events in the European Union, Japan, Switzerland, and the United States, reported lead investigator Marsha A. Wilcox, Sc.D., and colleagues at i3 Drug Safety, in Waltham, Mass.

From Nov. 1, 1999, through April 30, 2005, 60,267 patients were treated with oseltamivir and 175,933 received no antivirals. The two cohorts were balanced for a variety of baseline variables including age, sex, health plan region, index date, number of hospitalizations, and vaccinations for influenza and pneumococcus during the 6 months prior to diagnosis.

The incidence of any neuropsychiatric event was 3.8% in the oseltamivir group and 4.3% in those not treated with antivirals (exposure-adjusted odds ratio 0.89).

The incidence was also comparable for major neuropsychiatric events (3.4% vs. 3.7%; OR 0.89) and for central nervous system stimulation events (2.5% vs. 2.8%; OR 0.88), the investigators reported.

The conference was sponsored by the American Society for Microbiology.

Dr. Wilcox did not disclose any relevant conflicts of interest.

CHICAGO — Lichen planus is a tough disorder to treat and requires a strong commitment to patient education and follow-up, Dr. Lynette J. Margesson said at a conference on vulvovaginal diseases.

Lichen planus is an inflammatory, lymphocyte-mediated mucocutaneous disorder of an unknown cause that is relatively uncommon in the vulvovaginal area, and is too often missed. It usually involves the skin and less commonly the oral mucosa, scalp, nails, eyes, esophagus, bladder, larynx, and anus.

About 1% of the population has oral lichen planus. Recent studies have shown that up to 70% of women with oral lichen planus have genital involvement. Up to 44% can be asymptomatic, said Dr. Margesson of Dartmouth Medical School, Hanover, N.H.

Complications include scarring, loss of any or all of the vulvar structures, narrowing of the introitus, psychosexual problems, and synechiae and scarring that can eventually obliterate the vaginal space. Vulvar lichen planus is often confused with lichen sclerosus and, like that disease, is associated with an increased risk (3%–4%) of squamous cell carcinoma.

Prognosis is notoriously unpredictable, with about 75% of patients having improvement in symptoms and 10% having resolution of clinical signs without scarring, Dr. Margesson said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology. Patient education needs to be optimistic, even though there is often no “cure.” Some patients can go into remission permanently, but most have a tendency to relapse. Long-term follow-up is needed for compliance and cancer surveillance.

“Noncompliance is a big problem,” Dr. Margesson said. “They come back and their vulva is dying.”

Upon presentation, most patients complain of soreness, pain, and itching, which can be mild to moderate in the papular form and severe in the hypertrophic form.

On physical exam, the classic pattern on dry, keratinized skin includes raised, reddish brown to purple, well-defined, dry papules with fine lacy white streaks, referred to as Wickham's striae, on the surface.

Erosive lichen planus often shows deep red, glazed lesions around the posterior vestibule with associated loss of architecture and scarring. A whitish scalloped or reticulated edge to these lesions is a classic feature that is not present in lichen sclerosus and can help make the diagnosis of lichen planus, Dr. Margesson said. Oral involvement is seen in about 60% of these patients, with the same lacy reticulated pattern, plus varying degrees of ulceration and erosion present on the buccal or gingival mucosa and tongue. The hypertrophic form is the least common, and looks very much like thick lichen sclerosus on the vulva, with thickened, white, scarred skin and loss of normal architecture.

Regular histopathology biopsies are often unreliable, so Dr. Margesson recommends performing biopsies for both histopathology and direct immunofluorescence.

Nonspecific treatments include education and support, stopping all irritants, restoring the epidermal barrier, and offering psychosexual support, as these patients are usually sexually dysfunctional, she said.

Topical corticosteroids to suppress inflammation are the cornerstone of treatment. Dr. Margesson prefers clobetasol or halobetasol 0.05% ointment used very sparingly daily in a thin film for 8–12 weeks for the mucous membranes of the vulva, and 1–3 times a week for maintenance. Topical tacrolimus (Protopic) 0.1% ointment can be helpful, but this is an off-label use, and it should be applied sparingly as it may burn, she said.

Clobetasol or halobetasol ointment, or tacrolimus compounded in a 0.1% cream, can be used nightly intravaginally. Hydrocortisone acetate is available as a 25-mg suppository. A compounded hydrocortisone acetate suppository, 100–500 mg, used at bedtime for 2 weeks, can be given for severe vaginal disease, but adrenal suppression is possible. After 2 weeks, the dose is decreased, depending on the response.

For severe lichen planus, Dr. Margesson finds intramuscular triamcinolone acetonide 1 mg/kg every 4 weeks for 3–4 months is a better tolerated alternative to prednisone. Other effective drugs include methotrexate 5–10 mg per week or cyclosporine 4–5 mg/kg, but the latter should be limited to 2–3 months of treatment. Mycophenolate mofetil (CellCept) has been used up to 3 g per day, and recent studies suggest the use of etanercept (Enbrel) 50 mg subcutaneously twice weekly.

Surgery may be needed for significant scarring or vaginal adhesions, but these can recur. Dilators used nightly are important in these cases, and for vaginal stenosis, she said.

Many unanswered questions remain regarding lichen planus, Dr. Margesson said. They include the precise length of therapy, remission rate, best maintenance therapy, and long-term surveillance plan, whether treatment is needed in asymptomatic patients, which patients will go on to get squamous cell carcinoma, and what factors trigger lichen planus.

CHICAGO — Lichen planus is a tough disorder to treat and requires a strong commitment to patient education and follow-up, Dr. Lynette J. Margesson said at a conference on vulvovaginal diseases.

Lichen planus is an inflammatory, lymphocyte-mediated mucocutaneous disorder of an unknown cause that is relatively uncommon in the vulvovaginal area, and is too often missed. It usually involves the skin and less commonly the oral mucosa, scalp, nails, eyes, esophagus, bladder, larynx, and anus.

About 1% of the population has oral lichen planus. Recent studies have shown that up to 70% of women with oral lichen planus have genital involvement. Up to 44% can be asymptomatic, said Dr. Margesson of Dartmouth Medical School, Hanover, N.H.

Complications include scarring, loss of any or all of the vulvar structures, narrowing of the introitus, psychosexual problems, and synechiae and scarring that can eventually obliterate the vaginal space. Vulvar lichen planus is often confused with lichen sclerosus and, like that disease, is associated with an increased risk (3%–4%) of squamous cell carcinoma.

Prognosis is notoriously unpredictable, with about 75% of patients having improvement in symptoms and 10% having resolution of clinical signs without scarring, Dr. Margesson said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology. Patient education needs to be optimistic, even though there is often no “cure.” Some patients can go into remission permanently, but most have a tendency to relapse. Long-term follow-up is needed for compliance and cancer surveillance.

“Noncompliance is a big problem,” Dr. Margesson said. “They come back and their vulva is dying.”

Upon presentation, most patients complain of soreness, pain, and itching, which can be mild to moderate in the papular form and severe in the hypertrophic form.

On physical exam, the classic pattern on dry, keratinized skin includes raised, reddish brown to purple, well-defined, dry papules with fine lacy white streaks, referred to as Wickham's striae, on the surface.

Erosive lichen planus often shows deep red, glazed lesions around the posterior vestibule with associated loss of architecture and scarring. A whitish scalloped or reticulated edge to these lesions is a classic feature that is not present in lichen sclerosus and can help make the diagnosis of lichen planus, Dr. Margesson said. Oral involvement is seen in about 60% of these patients, with the same lacy reticulated pattern, plus varying degrees of ulceration and erosion present on the buccal or gingival mucosa and tongue. The hypertrophic form is the least common, and looks very much like thick lichen sclerosus on the vulva, with thickened, white, scarred skin and loss of normal architecture.

Regular histopathology biopsies are often unreliable, so Dr. Margesson recommends performing biopsies for both histopathology and direct immunofluorescence.

Nonspecific treatments include education and support, stopping all irritants, restoring the epidermal barrier, and offering psychosexual support, as these patients are usually sexually dysfunctional, she said.

Topical corticosteroids to suppress inflammation are the cornerstone of treatment. Dr. Margesson prefers clobetasol or halobetasol 0.05% ointment used very sparingly daily in a thin film for 8–12 weeks for the mucous membranes of the vulva, and 1–3 times a week for maintenance. Topical tacrolimus (Protopic) 0.1% ointment can be helpful, but this is an off-label use, and it should be applied sparingly as it may burn, she said.

Clobetasol or halobetasol ointment, or tacrolimus compounded in a 0.1% cream, can be used nightly intravaginally. Hydrocortisone acetate is available as a 25-mg suppository. A compounded hydrocortisone acetate suppository, 100–500 mg, used at bedtime for 2 weeks, can be given for severe vaginal disease, but adrenal suppression is possible. After 2 weeks, the dose is decreased, depending on the response.

For severe lichen planus, Dr. Margesson finds intramuscular triamcinolone acetonide 1 mg/kg every 4 weeks for 3–4 months is a better tolerated alternative to prednisone. Other effective drugs include methotrexate 5–10 mg per week or cyclosporine 4–5 mg/kg, but the latter should be limited to 2–3 months of treatment. Mycophenolate mofetil (CellCept) has been used up to 3 g per day, and recent studies suggest the use of etanercept (Enbrel) 50 mg subcutaneously twice weekly.

Surgery may be needed for significant scarring or vaginal adhesions, but these can recur. Dilators used nightly are important in these cases, and for vaginal stenosis, she said.

Many unanswered questions remain regarding lichen planus, Dr. Margesson said. They include the precise length of therapy, remission rate, best maintenance therapy, and long-term surveillance plan, whether treatment is needed in asymptomatic patients, which patients will go on to get squamous cell carcinoma, and what factors trigger lichen planus.

CHICAGO — Lichen planus is a tough disorder to treat and requires a strong commitment to patient education and follow-up, Dr. Lynette J. Margesson said at a conference on vulvovaginal diseases.

Lichen planus is an inflammatory, lymphocyte-mediated mucocutaneous disorder of an unknown cause that is relatively uncommon in the vulvovaginal area, and is too often missed. It usually involves the skin and less commonly the oral mucosa, scalp, nails, eyes, esophagus, bladder, larynx, and anus.

About 1% of the population has oral lichen planus. Recent studies have shown that up to 70% of women with oral lichen planus have genital involvement. Up to 44% can be asymptomatic, said Dr. Margesson of Dartmouth Medical School, Hanover, N.H.

Complications include scarring, loss of any or all of the vulvar structures, narrowing of the introitus, psychosexual problems, and synechiae and scarring that can eventually obliterate the vaginal space. Vulvar lichen planus is often confused with lichen sclerosus and, like that disease, is associated with an increased risk (3%–4%) of squamous cell carcinoma.

Prognosis is notoriously unpredictable, with about 75% of patients having improvement in symptoms and 10% having resolution of clinical signs without scarring, Dr. Margesson said at the conference, which was sponsored by the American Society for Colposcopy and Cervical Pathology. Patient education needs to be optimistic, even though there is often no “cure.” Some patients can go into remission permanently, but most have a tendency to relapse. Long-term follow-up is needed for compliance and cancer surveillance.

“Noncompliance is a big problem,” Dr. Margesson said. “They come back and their vulva is dying.”

Upon presentation, most patients complain of soreness, pain, and itching, which can be mild to moderate in the papular form and severe in the hypertrophic form.

On physical exam, the classic pattern on dry, keratinized skin includes raised, reddish brown to purple, well-defined, dry papules with fine lacy white streaks, referred to as Wickham's striae, on the surface.

Erosive lichen planus often shows deep red, glazed lesions around the posterior vestibule with associated loss of architecture and scarring. A whitish scalloped or reticulated edge to these lesions is a classic feature that is not present in lichen sclerosus and can help make the diagnosis of lichen planus, Dr. Margesson said. Oral involvement is seen in about 60% of these patients, with the same lacy reticulated pattern, plus varying degrees of ulceration and erosion present on the buccal or gingival mucosa and tongue. The hypertrophic form is the least common, and looks very much like thick lichen sclerosus on the vulva, with thickened, white, scarred skin and loss of normal architecture.

Regular histopathology biopsies are often unreliable, so Dr. Margesson recommends performing biopsies for both histopathology and direct immunofluorescence.

Nonspecific treatments include education and support, stopping all irritants, restoring the epidermal barrier, and offering psychosexual support, as these patients are usually sexually dysfunctional, she said.

Topical corticosteroids to suppress inflammation are the cornerstone of treatment. Dr. Margesson prefers clobetasol or halobetasol 0.05% ointment used very sparingly daily in a thin film for 8–12 weeks for the mucous membranes of the vulva, and 1–3 times a week for maintenance. Topical tacrolimus (Protopic) 0.1% ointment can be helpful, but this is an off-label use, and it should be applied sparingly as it may burn, she said.

Clobetasol or halobetasol ointment, or tacrolimus compounded in a 0.1% cream, can be used nightly intravaginally. Hydrocortisone acetate is available as a 25-mg suppository. A compounded hydrocortisone acetate suppository, 100–500 mg, used at bedtime for 2 weeks, can be given for severe vaginal disease, but adrenal suppression is possible. After 2 weeks, the dose is decreased, depending on the response.

For severe lichen planus, Dr. Margesson finds intramuscular triamcinolone acetonide 1 mg/kg every 4 weeks for 3–4 months is a better tolerated alternative to prednisone. Other effective drugs include methotrexate 5–10 mg per week or cyclosporine 4–5 mg/kg, but the latter should be limited to 2–3 months of treatment. Mycophenolate mofetil (CellCept) has been used up to 3 g per day, and recent studies suggest the use of etanercept (Enbrel) 50 mg subcutaneously twice weekly.

Surgery may be needed for significant scarring or vaginal adhesions, but these can recur. Dilators used nightly are important in these cases, and for vaginal stenosis, she said.

Many unanswered questions remain regarding lichen planus, Dr. Margesson said. They include the precise length of therapy, remission rate, best maintenance therapy, and long-term surveillance plan, whether treatment is needed in asymptomatic patients, which patients will go on to get squamous cell carcinoma, and what factors trigger lichen planus.

CHICAGO — Individuals with both Alzheimer's disease and hypertension had significantly lower blood flow in multiple regions of the brain on magnetic resonance imaging, compared with their counterparts without hypertension, investigators reported in a poster at the annual meeting of the Radiological Society of North America.

In the study of 88 participants with a mean age of 83 years, brain perfusion also was significantly lower in controls with normal cognitive function and hypertension, compared with their counterparts without hypertension. A trend toward lower perfusion in individuals with mild cognitive impairment and hypertension did not achieve statistical significance.

The data are consistent with recent studies showing that Alzheimer's patients with vascular disease in general had faster progression of symptoms, Dr. Oscar L. Lopez said in an interview. In addition, multiple studies in the literature have shown that hypertension—especially in midlife—is a risk factor for Alzheimer's disease.

The same researchers also recently showed that normal subjects with hypertension had diminished cerebral blood flow in cerebral areas that are usually involved in Alzheimer's disease (Stroke 2008 Jan. 3[doi:10.1161/STROKEAHA.107.495457]). This does not mean that all individuals with hypertension will develop dementia, but in those who are destined to have Alzheimer's disease, dementia symptoms may appear earlier than in those without hypertension, said Dr. Lopez, who is a professor of neurology at the University of Pittsburgh and principal investigator in the Cardiovascular Health Study (CHS) Cognition Study.

“Both studies emphasized the importance of adequate treatment for hypertension,” he said. “In cognitively normal individuals, hypertension treatment may delay the onset of the dementia, and in Alzheimer's disease patients, it may ameliorate the rate of decline.”

Study participants were recruited from the ongoing CHS Cognition Study, and included 48 controls with normal cognitive function (including 10 with hypertension), 20 individuals with Alzheimer's (including 10 with hypertension), and 20 individuals with mild cognitive impairment (including 10 with hypertension). Hypertension, defined as a blood pressure greater than 140/90 mm Hg, was treated in all patients.

All participants were scanned with T1-weighted and arterial spin-labeled MRI at 1.5T. This quantitative technique uses no external contrast and uses kinetics modeling equations to compute cerebral blood flow based on MR signal intensity. Cerebral blood flow values are expressed in milliliters of blood per 100 g of tissue per minute, said lead investigator Cyrus Raji, who is a student at University of Pittsburgh, where the study was conducted. The study was funded by the National Institute on Aging, and no relevant financial conflicts of interest were disclosed.

Overall, cerebral blood flow was lowest in individuals with Alzheimer's disease and hypertension (34.8 mL per 100 g/min), compared with controls with hypertension (41.4) and those with mild cognitive impairment and hypertension (47.8).

Notably, decreased flow in Alzheimer's participants with hypertension occurred in the posterior cingulate gyrus (35.9), lateral prefrontal cortex (29.5), and left thalamus (28.9). Corresponding cerebral blood flow values were 52.3, 39.4, and 38.5 for hypertensive controls and 47.8, 36.3, and 58.1 for hypertensive participants with mild cognitive impairment (MCI).

Cerebral blood flow to the left hippocampus was reduced in participants with hypertension in the Alzheimer's (33.5), control (38.7), and MCI (47.7) groups, compared with their counterparts without hypertension (41.2, 42.4, and 57.2, respectively). This finding may have implications for Alzheimer's development, because the hippocampus is an early site of Alzheimer's pathology.

Hypertension and brain vascular disease may be major risk factors for dementia, said senior author Dr. Louis Kuller, also of the University of Pittsburgh, in an interview. “Excellent control of elevated blood pressure or prevention of hypertension, especially in 'middle ages' prior to vascular brain damage, may be the most important preventable determinant for dementia.”

CHICAGO — Individuals with both Alzheimer's disease and hypertension had significantly lower blood flow in multiple regions of the brain on magnetic resonance imaging, compared with their counterparts without hypertension, investigators reported in a poster at the annual meeting of the Radiological Society of North America.

In the study of 88 participants with a mean age of 83 years, brain perfusion also was significantly lower in controls with normal cognitive function and hypertension, compared with their counterparts without hypertension. A trend toward lower perfusion in individuals with mild cognitive impairment and hypertension did not achieve statistical significance.

The data are consistent with recent studies showing that Alzheimer's patients with vascular disease in general had faster progression of symptoms, Dr. Oscar L. Lopez said in an interview. In addition, multiple studies in the literature have shown that hypertension—especially in midlife—is a risk factor for Alzheimer's disease.

The same researchers also recently showed that normal subjects with hypertension had diminished cerebral blood flow in cerebral areas that are usually involved in Alzheimer's disease (Stroke 2008 Jan. 3[doi:10.1161/STROKEAHA.107.495457]). This does not mean that all individuals with hypertension will develop dementia, but in those who are destined to have Alzheimer's disease, dementia symptoms may appear earlier than in those without hypertension, said Dr. Lopez, who is a professor of neurology at the University of Pittsburgh and principal investigator in the Cardiovascular Health Study (CHS) Cognition Study.

“Both studies emphasized the importance of adequate treatment for hypertension,” he said. “In cognitively normal individuals, hypertension treatment may delay the onset of the dementia, and in Alzheimer's disease patients, it may ameliorate the rate of decline.”

Study participants were recruited from the ongoing CHS Cognition Study, and included 48 controls with normal cognitive function (including 10 with hypertension), 20 individuals with Alzheimer's (including 10 with hypertension), and 20 individuals with mild cognitive impairment (including 10 with hypertension). Hypertension, defined as a blood pressure greater than 140/90 mm Hg, was treated in all patients.

All participants were scanned with T1-weighted and arterial spin-labeled MRI at 1.5T. This quantitative technique uses no external contrast and uses kinetics modeling equations to compute cerebral blood flow based on MR signal intensity. Cerebral blood flow values are expressed in milliliters of blood per 100 g of tissue per minute, said lead investigator Cyrus Raji, who is a student at University of Pittsburgh, where the study was conducted. The study was funded by the National Institute on Aging, and no relevant financial conflicts of interest were disclosed.

Overall, cerebral blood flow was lowest in individuals with Alzheimer's disease and hypertension (34.8 mL per 100 g/min), compared with controls with hypertension (41.4) and those with mild cognitive impairment and hypertension (47.8).

Notably, decreased flow in Alzheimer's participants with hypertension occurred in the posterior cingulate gyrus (35.9), lateral prefrontal cortex (29.5), and left thalamus (28.9). Corresponding cerebral blood flow values were 52.3, 39.4, and 38.5 for hypertensive controls and 47.8, 36.3, and 58.1 for hypertensive participants with mild cognitive impairment (MCI).

Cerebral blood flow to the left hippocampus was reduced in participants with hypertension in the Alzheimer's (33.5), control (38.7), and MCI (47.7) groups, compared with their counterparts without hypertension (41.2, 42.4, and 57.2, respectively). This finding may have implications for Alzheimer's development, because the hippocampus is an early site of Alzheimer's pathology.

Hypertension and brain vascular disease may be major risk factors for dementia, said senior author Dr. Louis Kuller, also of the University of Pittsburgh, in an interview. “Excellent control of elevated blood pressure or prevention of hypertension, especially in 'middle ages' prior to vascular brain damage, may be the most important preventable determinant for dementia.”

CHICAGO — Individuals with both Alzheimer's disease and hypertension had significantly lower blood flow in multiple regions of the brain on magnetic resonance imaging, compared with their counterparts without hypertension, investigators reported in a poster at the annual meeting of the Radiological Society of North America.

In the study of 88 participants with a mean age of 83 years, brain perfusion also was significantly lower in controls with normal cognitive function and hypertension, compared with their counterparts without hypertension. A trend toward lower perfusion in individuals with mild cognitive impairment and hypertension did not achieve statistical significance.

The data are consistent with recent studies showing that Alzheimer's patients with vascular disease in general had faster progression of symptoms, Dr. Oscar L. Lopez said in an interview. In addition, multiple studies in the literature have shown that hypertension—especially in midlife—is a risk factor for Alzheimer's disease.

The same researchers also recently showed that normal subjects with hypertension had diminished cerebral blood flow in cerebral areas that are usually involved in Alzheimer's disease (Stroke 2008 Jan. 3[doi:10.1161/STROKEAHA.107.495457]). This does not mean that all individuals with hypertension will develop dementia, but in those who are destined to have Alzheimer's disease, dementia symptoms may appear earlier than in those without hypertension, said Dr. Lopez, who is a professor of neurology at the University of Pittsburgh and principal investigator in the Cardiovascular Health Study (CHS) Cognition Study.

“Both studies emphasized the importance of adequate treatment for hypertension,” he said. “In cognitively normal individuals, hypertension treatment may delay the onset of the dementia, and in Alzheimer's disease patients, it may ameliorate the rate of decline.”

Study participants were recruited from the ongoing CHS Cognition Study, and included 48 controls with normal cognitive function (including 10 with hypertension), 20 individuals with Alzheimer's (including 10 with hypertension), and 20 individuals with mild cognitive impairment (including 10 with hypertension). Hypertension, defined as a blood pressure greater than 140/90 mm Hg, was treated in all patients.

All participants were scanned with T1-weighted and arterial spin-labeled MRI at 1.5T. This quantitative technique uses no external contrast and uses kinetics modeling equations to compute cerebral blood flow based on MR signal intensity. Cerebral blood flow values are expressed in milliliters of blood per 100 g of tissue per minute, said lead investigator Cyrus Raji, who is a student at University of Pittsburgh, where the study was conducted. The study was funded by the National Institute on Aging, and no relevant financial conflicts of interest were disclosed.

Overall, cerebral blood flow was lowest in individuals with Alzheimer's disease and hypertension (34.8 mL per 100 g/min), compared with controls with hypertension (41.4) and those with mild cognitive impairment and hypertension (47.8).

Notably, decreased flow in Alzheimer's participants with hypertension occurred in the posterior cingulate gyrus (35.9), lateral prefrontal cortex (29.5), and left thalamus (28.9). Corresponding cerebral blood flow values were 52.3, 39.4, and 38.5 for hypertensive controls and 47.8, 36.3, and 58.1 for hypertensive participants with mild cognitive impairment (MCI).

Cerebral blood flow to the left hippocampus was reduced in participants with hypertension in the Alzheimer's (33.5), control (38.7), and MCI (47.7) groups, compared with their counterparts without hypertension (41.2, 42.4, and 57.2, respectively). This finding may have implications for Alzheimer's development, because the hippocampus is an early site of Alzheimer's pathology.

Hypertension and brain vascular disease may be major risk factors for dementia, said senior author Dr. Louis Kuller, also of the University of Pittsburgh, in an interview. “Excellent control of elevated blood pressure or prevention of hypertension, especially in 'middle ages' prior to vascular brain damage, may be the most important preventable determinant for dementia.”

CHICAGO — A second multicenter trial has shown that noninvasive CT angiography is highly accurate in assessing coronary artery disease when compared with conventional invasive angiography.

The per-vessel negative predictive value of 64-slice coronary CT angiography (CCTA) was 97% for identifying blockages greater than 50%, and 99% for blockages greater than 70%, when measured in 232 patients with typical or atypical chest pain in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Positive predictive values were 51% and 33%, respectively, Dr. James K. Min and his associates reported at the annual meeting of the Radiological Society of North America.

“The ACCURACY results [obtained] in a prospective, multicenter fashion definitively establish the high diagnostic accuracy and high negative predictive value of 64-detector-row CT angiography in chest pain patients with intermediate prevalence of coronary artery disease,” said Dr. Min, director of the cardiac CT laboratory at New York-Presbyterian Hospital.

The findings echo those of the recent Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography (CORE-64) trial, in which CT angiography had a 91% positive predictive value and an 83% negative predictive value for identifying significant coronary artery stenoses. CORE-64 was the first large, multicenter trial of the 64-slice technology for coronary angiography, but was criticized by some attendees at the annual scientific sessions of the American Heart Association where it was presented (CARDIOLOGY NEWS, Dec. 2007, p. 1). Concerns were raised that the radiation dose from repeated CT scans could pose a potential cancer risk. No such concerns were raised at the radiology meeting.

To reduce the amount of radiation given to patients in the ACCURACY trial, investigators used a radiation dose-reduction algorithm called EKG modulation that reduces CT angiography radiation by about 40%, Dr. Min said in an interview. The radiation dose per patient was about 10–15 millisieverts (mSv), which is about twice that of an invasive coronary angiogram and about half that of a noninvasive thallium stress test.

Since the trial began, a new algorithm called perspective axial gating has been commercially released and is reported to reduce exposure by 90%, to about 2–4 mSv. Both algorithms work by activating the CT scanner during select parts of the cardiac cycle only, Dr. Min said. For comparison, New York City residents are exposed to about 3 mSv of radiation annually through background exposure.

Neither study used CT angiography for screening. “I believe very emphatically that the data to date don't support CT angiography as a screening tool at all,” Dr. Min said. “In asymptomatic patients, we don't have any data of what to do with the results, and if treatment benefits them.”

CT angiography is of greatest benefit for patients without known coronary disease who have low or intermediate pretest risk. “If you have a high pretest suspicion that someone has coronary artery disease, then direct progression to invasive coronary angiography or even myocardial perfusion imaging is probably a better alternative,” he said.

The ACCURACY trial was unique in that it included all coronary artery segments in its analysis and all patients irrespective of their baseline coronary calcium score. In the CORE-64 trial, stented segments were excluded, as were patients with a calcium score higher than 600. As a result, the ACCURACY findings of high diagnostic accuracy are even more impressive and representative of actual clinical usage, Dr. Min said.

Between May 2006 and January 2007, ACCURACY investigators performed CCTA prior to conventional quantitative coronary angiography (QCA) on 232 patients who had typical or atypical chest pain and had been referred for evaluation at 16 U.S. centers. The images were obtained on a GE Healthcare LightSpeed VCT CT scanner, and analyzed at 15 different locations throughout the coronary tree. The investigators used equipment made by GE Healthcare, which sponsored the study. Dr. Min is on the speakers' bureau for GE Healthcare.

Three independent radiologists interpreted the CCTA images, and one independent radiologist interpreted the QCA images, Dr. Min said.

The patients' mean age was 57 years (range 31–82 years); 138 were male, 203 were white, and 13 were black, and their average body mass index was 31 kg/m

QCA detected 82 blockages greater than 50% in 55 patients and 31 blockages greater than 70% in 34 patients.

For noninvasive CCTA, per-patient sensitivity was 93% and specificity was 82% for blockages greater than 50%; sensitivity was 91% and specificity was 84% for blockages greater than 70%, Dr. Min said.

CHICAGO — A second multicenter trial has shown that noninvasive CT angiography is highly accurate in assessing coronary artery disease when compared with conventional invasive angiography.

The per-vessel negative predictive value of 64-slice coronary CT angiography (CCTA) was 97% for identifying blockages greater than 50%, and 99% for blockages greater than 70%, when measured in 232 patients with typical or atypical chest pain in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Positive predictive values were 51% and 33%, respectively, Dr. James K. Min and his associates reported at the annual meeting of the Radiological Society of North America.

“The ACCURACY results [obtained] in a prospective, multicenter fashion definitively establish the high diagnostic accuracy and high negative predictive value of 64-detector-row CT angiography in chest pain patients with intermediate prevalence of coronary artery disease,” said Dr. Min, director of the cardiac CT laboratory at New York-Presbyterian Hospital.

The findings echo those of the recent Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography (CORE-64) trial, in which CT angiography had a 91% positive predictive value and an 83% negative predictive value for identifying significant coronary artery stenoses. CORE-64 was the first large, multicenter trial of the 64-slice technology for coronary angiography, but was criticized by some attendees at the annual scientific sessions of the American Heart Association where it was presented (CARDIOLOGY NEWS, Dec. 2007, p. 1). Concerns were raised that the radiation dose from repeated CT scans could pose a potential cancer risk. No such concerns were raised at the radiology meeting.

To reduce the amount of radiation given to patients in the ACCURACY trial, investigators used a radiation dose-reduction algorithm called EKG modulation that reduces CT angiography radiation by about 40%, Dr. Min said in an interview. The radiation dose per patient was about 10–15 millisieverts (mSv), which is about twice that of an invasive coronary angiogram and about half that of a noninvasive thallium stress test.

Since the trial began, a new algorithm called perspective axial gating has been commercially released and is reported to reduce exposure by 90%, to about 2–4 mSv. Both algorithms work by activating the CT scanner during select parts of the cardiac cycle only, Dr. Min said. For comparison, New York City residents are exposed to about 3 mSv of radiation annually through background exposure.

Neither study used CT angiography for screening. “I believe very emphatically that the data to date don't support CT angiography as a screening tool at all,” Dr. Min said. “In asymptomatic patients, we don't have any data of what to do with the results, and if treatment benefits them.”

CT angiography is of greatest benefit for patients without known coronary disease who have low or intermediate pretest risk. “If you have a high pretest suspicion that someone has coronary artery disease, then direct progression to invasive coronary angiography or even myocardial perfusion imaging is probably a better alternative,” he said.

The ACCURACY trial was unique in that it included all coronary artery segments in its analysis and all patients irrespective of their baseline coronary calcium score. In the CORE-64 trial, stented segments were excluded, as were patients with a calcium score higher than 600. As a result, the ACCURACY findings of high diagnostic accuracy are even more impressive and representative of actual clinical usage, Dr. Min said.

Between May 2006 and January 2007, ACCURACY investigators performed CCTA prior to conventional quantitative coronary angiography (QCA) on 232 patients who had typical or atypical chest pain and had been referred for evaluation at 16 U.S. centers. The images were obtained on a GE Healthcare LightSpeed VCT CT scanner, and analyzed at 15 different locations throughout the coronary tree. The investigators used equipment made by GE Healthcare, which sponsored the study. Dr. Min is on the speakers' bureau for GE Healthcare.

Three independent radiologists interpreted the CCTA images, and one independent radiologist interpreted the QCA images, Dr. Min said.

The patients' mean age was 57 years (range 31–82 years); 138 were male, 203 were white, and 13 were black, and their average body mass index was 31 kg/m

QCA detected 82 blockages greater than 50% in 55 patients and 31 blockages greater than 70% in 34 patients.

For noninvasive CCTA, per-patient sensitivity was 93% and specificity was 82% for blockages greater than 50%; sensitivity was 91% and specificity was 84% for blockages greater than 70%, Dr. Min said.

CHICAGO — A second multicenter trial has shown that noninvasive CT angiography is highly accurate in assessing coronary artery disease when compared with conventional invasive angiography.

The per-vessel negative predictive value of 64-slice coronary CT angiography (CCTA) was 97% for identifying blockages greater than 50%, and 99% for blockages greater than 70%, when measured in 232 patients with typical or atypical chest pain in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Positive predictive values were 51% and 33%, respectively, Dr. James K. Min and his associates reported at the annual meeting of the Radiological Society of North America.

“The ACCURACY results [obtained] in a prospective, multicenter fashion definitively establish the high diagnostic accuracy and high negative predictive value of 64-detector-row CT angiography in chest pain patients with intermediate prevalence of coronary artery disease,” said Dr. Min, director of the cardiac CT laboratory at New York-Presbyterian Hospital.

The findings echo those of the recent Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography (CORE-64) trial, in which CT angiography had a 91% positive predictive value and an 83% negative predictive value for identifying significant coronary artery stenoses. CORE-64 was the first large, multicenter trial of the 64-slice technology for coronary angiography, but was criticized by some attendees at the annual scientific sessions of the American Heart Association where it was presented (CARDIOLOGY NEWS, Dec. 2007, p. 1). Concerns were raised that the radiation dose from repeated CT scans could pose a potential cancer risk. No such concerns were raised at the radiology meeting.

To reduce the amount of radiation given to patients in the ACCURACY trial, investigators used a radiation dose-reduction algorithm called EKG modulation that reduces CT angiography radiation by about 40%, Dr. Min said in an interview. The radiation dose per patient was about 10–15 millisieverts (mSv), which is about twice that of an invasive coronary angiogram and about half that of a noninvasive thallium stress test.

Since the trial began, a new algorithm called perspective axial gating has been commercially released and is reported to reduce exposure by 90%, to about 2–4 mSv. Both algorithms work by activating the CT scanner during select parts of the cardiac cycle only, Dr. Min said. For comparison, New York City residents are exposed to about 3 mSv of radiation annually through background exposure.

Neither study used CT angiography for screening. “I believe very emphatically that the data to date don't support CT angiography as a screening tool at all,” Dr. Min said. “In asymptomatic patients, we don't have any data of what to do with the results, and if treatment benefits them.”

CT angiography is of greatest benefit for patients without known coronary disease who have low or intermediate pretest risk. “If you have a high pretest suspicion that someone has coronary artery disease, then direct progression to invasive coronary angiography or even myocardial perfusion imaging is probably a better alternative,” he said.

The ACCURACY trial was unique in that it included all coronary artery segments in its analysis and all patients irrespective of their baseline coronary calcium score. In the CORE-64 trial, stented segments were excluded, as were patients with a calcium score higher than 600. As a result, the ACCURACY findings of high diagnostic accuracy are even more impressive and representative of actual clinical usage, Dr. Min said.

Between May 2006 and January 2007, ACCURACY investigators performed CCTA prior to conventional quantitative coronary angiography (QCA) on 232 patients who had typical or atypical chest pain and had been referred for evaluation at 16 U.S. centers. The images were obtained on a GE Healthcare LightSpeed VCT CT scanner, and analyzed at 15 different locations throughout the coronary tree. The investigators used equipment made by GE Healthcare, which sponsored the study. Dr. Min is on the speakers' bureau for GE Healthcare.

Three independent radiologists interpreted the CCTA images, and one independent radiologist interpreted the QCA images, Dr. Min said.

The patients' mean age was 57 years (range 31–82 years); 138 were male, 203 were white, and 13 were black, and their average body mass index was 31 kg/m

QCA detected 82 blockages greater than 50% in 55 patients and 31 blockages greater than 70% in 34 patients.

For noninvasive CCTA, per-patient sensitivity was 93% and specificity was 82% for blockages greater than 50%; sensitivity was 91% and specificity was 84% for blockages greater than 70%, Dr. Min said.

CHICAGO — A novel magnetic resonance imaging technique may have provided the proverbial smoking gun in the secondhand smoking debate.

Using helium-3 diffusion MRI, researchers at the University of Virginia in Charlottesville and the Children's Hospital of Philadelphia have for the first time identified structural damage in the lungs of individuals with high exposure to secondhand smoke.

The technique is similar to conventional MRI, except that the images are acquired after the patient inhales hyperpolarized helium. The scanner is a standard 1.5-tesla commercial scanner, but is modified by the addition of a multinuclear imaging package and a radiofrequency coil tuned to the helium frequency of 48.5 MHz. The intensity of the MR signal is enhanced by a factor of more than 100,000 on a 1.5-tesla scanner and by a factor of 1 million on a 0.15-tesla scanner. This allows for the evaluation of lung structures on a microscopic level, lead investigator Chengbo Wang, Ph.D., said at the annual meeting of the Radiological Society of North America.

The MR images show how far the helium atoms diffuse inside the lungs over 1.5 seconds. In some smokers, the alveoli become enlarged and develop holes, allowing the helium atoms to infiltrate the lung microstructure to a greater extent. This is reflected in higher apparent diffusion coefficient (ADC) values, which have been shown to be larger when measured in emphysematous lungs, compared with healthy lungs (Radiology 2006;239:875–83).

For the study, 60 individuals underwent helium diffusion MRI after inhalation of 50 cc of hyperpolarized helium diluted with nitrogen to a total volume of approximately one-third of their forced vital capacity, as measured by spirometry on the day of imaging. In all, 23 individuals had low exposure, defined as never having lived with a smoker nor worked in an occupation with high exposure to secondhand smoke; 22 had high exposure, defined as at least 10 years' exposure at home or work; and 15 were current or former smokers.

At baseline, their age ranged from 41 to 79 years, and the range of percent-predicted forced expiratory volume in 1 second values was 86%–112% (low-exposure group), 79%–120% (high-exposure group), and 49%–121% (current or former smokers). The threshold for an elevated ADC was set as 0.024 cm

Only 1 (4%) of 23 participants with low exposure had an elevated ADC value, compared with 6 (27%) of 22 participants with high exposure and 10 (67%) of 15 smokers. The difference in ADC values was significant between smokers and the low-exposure group and between the high- and low-exposure groups.

As for why some smokers had normal ADC values, Dr. Wang said that they may be genetically wired to be less sensitive to the harmful effects of smoking, while others are more sensitive and incur more lung damage. The study was funded by the National Institutes of Health, the Flight Attendant Medical Research Institute, and the Commonwealth of Virginia Technology Research Fund. Siemens Medical Solutions provided the scanner. The study researchers did not disclose any personal conflicts of interest.

Shown here from left to right are lungs with low exposure to secondhand smoke, high exposure to secondhand smoke, and in smokers. The red color indicates normal alveoli. Radiological Society of North America/Dr. Chengbo Wang

CHICAGO — A novel magnetic resonance imaging technique may have provided the proverbial smoking gun in the secondhand smoking debate.

Using helium-3 diffusion MRI, researchers at the University of Virginia in Charlottesville and the Children's Hospital of Philadelphia have for the first time identified structural damage in the lungs of individuals with high exposure to secondhand smoke.

The technique is similar to conventional MRI, except that the images are acquired after the patient inhales hyperpolarized helium. The scanner is a standard 1.5-tesla commercial scanner, but is modified by the addition of a multinuclear imaging package and a radiofrequency coil tuned to the helium frequency of 48.5 MHz. The intensity of the MR signal is enhanced by a factor of more than 100,000 on a 1.5-tesla scanner and by a factor of 1 million on a 0.15-tesla scanner. This allows for the evaluation of lung structures on a microscopic level, lead investigator Chengbo Wang, Ph.D., said at the annual meeting of the Radiological Society of North America.

The MR images show how far the helium atoms diffuse inside the lungs over 1.5 seconds. In some smokers, the alveoli become enlarged and develop holes, allowing the helium atoms to infiltrate the lung microstructure to a greater extent. This is reflected in higher apparent diffusion coefficient (ADC) values, which have been shown to be larger when measured in emphysematous lungs, compared with healthy lungs (Radiology 2006;239:875–83).

For the study, 60 individuals underwent helium diffusion MRI after inhalation of 50 cc of hyperpolarized helium diluted with nitrogen to a total volume of approximately one-third of their forced vital capacity, as measured by spirometry on the day of imaging. In all, 23 individuals had low exposure, defined as never having lived with a smoker nor worked in an occupation with high exposure to secondhand smoke; 22 had high exposure, defined as at least 10 years' exposure at home or work; and 15 were current or former smokers.

At baseline, their age ranged from 41 to 79 years, and the range of percent-predicted forced expiratory volume in 1 second values was 86%–112% (low-exposure group), 79%–120% (high-exposure group), and 49%–121% (current or former smokers). The threshold for an elevated ADC was set as 0.024 cm

Only 1 (4%) of 23 participants with low exposure had an elevated ADC value, compared with 6 (27%) of 22 participants with high exposure and 10 (67%) of 15 smokers. The difference in ADC values was significant between smokers and the low-exposure group and between the high- and low-exposure groups.

As for why some smokers had normal ADC values, Dr. Wang said that they may be genetically wired to be less sensitive to the harmful effects of smoking, while others are more sensitive and incur more lung damage. The study was funded by the National Institutes of Health, the Flight Attendant Medical Research Institute, and the Commonwealth of Virginia Technology Research Fund. Siemens Medical Solutions provided the scanner. The study researchers did not disclose any personal conflicts of interest.

Shown here from left to right are lungs with low exposure to secondhand smoke, high exposure to secondhand smoke, and in smokers. The red color indicates normal alveoli. Radiological Society of North America/Dr. Chengbo Wang

CHICAGO — A novel magnetic resonance imaging technique may have provided the proverbial smoking gun in the secondhand smoking debate.

Using helium-3 diffusion MRI, researchers at the University of Virginia in Charlottesville and the Children's Hospital of Philadelphia have for the first time identified structural damage in the lungs of individuals with high exposure to secondhand smoke.

The technique is similar to conventional MRI, except that the images are acquired after the patient inhales hyperpolarized helium. The scanner is a standard 1.5-tesla commercial scanner, but is modified by the addition of a multinuclear imaging package and a radiofrequency coil tuned to the helium frequency of 48.5 MHz. The intensity of the MR signal is enhanced by a factor of more than 100,000 on a 1.5-tesla scanner and by a factor of 1 million on a 0.15-tesla scanner. This allows for the evaluation of lung structures on a microscopic level, lead investigator Chengbo Wang, Ph.D., said at the annual meeting of the Radiological Society of North America.

The MR images show how far the helium atoms diffuse inside the lungs over 1.5 seconds. In some smokers, the alveoli become enlarged and develop holes, allowing the helium atoms to infiltrate the lung microstructure to a greater extent. This is reflected in higher apparent diffusion coefficient (ADC) values, which have been shown to be larger when measured in emphysematous lungs, compared with healthy lungs (Radiology 2006;239:875–83).

For the study, 60 individuals underwent helium diffusion MRI after inhalation of 50 cc of hyperpolarized helium diluted with nitrogen to a total volume of approximately one-third of their forced vital capacity, as measured by spirometry on the day of imaging. In all, 23 individuals had low exposure, defined as never having lived with a smoker nor worked in an occupation with high exposure to secondhand smoke; 22 had high exposure, defined as at least 10 years' exposure at home or work; and 15 were current or former smokers.

At baseline, their age ranged from 41 to 79 years, and the range of percent-predicted forced expiratory volume in 1 second values was 86%–112% (low-exposure group), 79%–120% (high-exposure group), and 49%–121% (current or former smokers). The threshold for an elevated ADC was set as 0.024 cm

Only 1 (4%) of 23 participants with low exposure had an elevated ADC value, compared with 6 (27%) of 22 participants with high exposure and 10 (67%) of 15 smokers. The difference in ADC values was significant between smokers and the low-exposure group and between the high- and low-exposure groups.

As for why some smokers had normal ADC values, Dr. Wang said that they may be genetically wired to be less sensitive to the harmful effects of smoking, while others are more sensitive and incur more lung damage. The study was funded by the National Institutes of Health, the Flight Attendant Medical Research Institute, and the Commonwealth of Virginia Technology Research Fund. Siemens Medical Solutions provided the scanner. The study researchers did not disclose any personal conflicts of interest.

Shown here from left to right are lungs with low exposure to secondhand smoke, high exposure to secondhand smoke, and in smokers. The red color indicates normal alveoli. Radiological Society of North America/Dr. Chengbo Wang

CHICAGO — Iodine contrast-enhanced digital mammography may be a useful and inexpensive alternative to follow-up magnetic resonance imaging in women with suspicious lesions on mammography, according to data presented at the annual meeting of the Radiological Society of North America.

The use of iodine-based contrast medium as an adjunct to mammography significantly reduced the average number of overlooked malignant lesions from 17 to 11, compared with digital mammography alone in a study of 70 women with 80 suspicious findings. Overlooked lesions were defined as malignant lesions with a Breast Imaging Reporting and Data System score of 3 or lower.

The biggest benefit of contrast-enhanced digital mammography (CEDM) was observed in women with dense breasts, said Dr. Ulrick Bick, department of radiology, Charité School of Medicine-Berlin. In all of the women, sensitivity improved from 43% with standard digital mammography to 62% with CEDM, and from 57% to 64% for women with American College of Radiology (ACR) density I-II breasts, and from 35% to 59% for women with ACR density III-IV breasts. Specificity decreased from 70% to 65%; 72% to 71%; and 69% to 62%, respectively.

“You are [not] going to see additional lesions compared with MRI, but you may have less trouble with false positives,” Dr. Bick said in an interview. “On MRI, you see a lot of small enhancing foci that may not be significant, and that may be different with iodine contrast. [There'll be fewer] false positives.”

In addition, iodine contrast is more widely available and less expensive than MRI. The main application for an iodine contrast-enhanced mammogram would be as an adjunct in cases in which a lesion is difficult to visualize on mammogram, typically because of dense breasts or lesions embedded in dense parenchyma, he said.

A receiver-operator analysis showed that all three independent readers saw an improvement with the addition of CEDM. The increase was significant for two of the three readers.

Of note was that two of the three readers used CEDM only to upgrade lesions to a higher probability of malignancy, whereas the third reader, who saw less benefit from CEDM, used it to downgrade lesions.

“This is something we also learned in a separate-reader study—if you don't see enhancement on CEDM, then you cannot use that to exclude malignancy,” Dr. Bick said. “This is a very important finding.”

Among the 80 suspicious findings at baseline, 50 were benign and 30 were malignant, including 25 invasive cancers and 5 ductal carcinoma in situ cancers. The lesions were fairly large, with an average size of 3.2 cm.

The images were acquired on modified Senographe 2000D (GE Healthcare) full-field digital mammography machine, and obtained before and 60, 120, and 180 seconds after injection of 1 mg/kg of iodine-based contrast medium (Ultravist 370, Schering, Germany). The machine was modified with a copper filter for iodine imaging, and a substraction imaging technique was used to visualize the contrast enhancement, Dr. Bick said. Interpretation of the images was done first without the CEDM images, then with them. The mean age of the women was 55 years.

Although severe adverse reactions to intravenous iodine contrast are rare, at about 1 in 10,000 patients, one woman had a moderate, but not life-threatening reaction to the contrast medium, said Dr. Bick, who disclosed no relevant conflicts of interest. Dr. Felix Diekmann, also of Charité School of Medicine-Berlin, led the study.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Iodine contrast-enhanced digital mammography may be a useful and inexpensive alternative to follow-up magnetic resonance imaging in women with suspicious lesions on mammography, according to data presented at the annual meeting of the Radiological Society of North America.

The use of iodine-based contrast medium as an adjunct to mammography significantly reduced the average number of overlooked malignant lesions from 17 to 11, compared with digital mammography alone in a study of 70 women with 80 suspicious findings. Overlooked lesions were defined as malignant lesions with a Breast Imaging Reporting and Data System score of 3 or lower.

The biggest benefit of contrast-enhanced digital mammography (CEDM) was observed in women with dense breasts, said Dr. Ulrick Bick, department of radiology, Charité School of Medicine-Berlin. In all of the women, sensitivity improved from 43% with standard digital mammography to 62% with CEDM, and from 57% to 64% for women with American College of Radiology (ACR) density I-II breasts, and from 35% to 59% for women with ACR density III-IV breasts. Specificity decreased from 70% to 65%; 72% to 71%; and 69% to 62%, respectively.

“You are [not] going to see additional lesions compared with MRI, but you may have less trouble with false positives,” Dr. Bick said in an interview. “On MRI, you see a lot of small enhancing foci that may not be significant, and that may be different with iodine contrast. [There'll be fewer] false positives.”

In addition, iodine contrast is more widely available and less expensive than MRI. The main application for an iodine contrast-enhanced mammogram would be as an adjunct in cases in which a lesion is difficult to visualize on mammogram, typically because of dense breasts or lesions embedded in dense parenchyma, he said.

A receiver-operator analysis showed that all three independent readers saw an improvement with the addition of CEDM. The increase was significant for two of the three readers.

Of note was that two of the three readers used CEDM only to upgrade lesions to a higher probability of malignancy, whereas the third reader, who saw less benefit from CEDM, used it to downgrade lesions.

“This is something we also learned in a separate-reader study—if you don't see enhancement on CEDM, then you cannot use that to exclude malignancy,” Dr. Bick said. “This is a very important finding.”

Among the 80 suspicious findings at baseline, 50 were benign and 30 were malignant, including 25 invasive cancers and 5 ductal carcinoma in situ cancers. The lesions were fairly large, with an average size of 3.2 cm.

The images were acquired on modified Senographe 2000D (GE Healthcare) full-field digital mammography machine, and obtained before and 60, 120, and 180 seconds after injection of 1 mg/kg of iodine-based contrast medium (Ultravist 370, Schering, Germany). The machine was modified with a copper filter for iodine imaging, and a substraction imaging technique was used to visualize the contrast enhancement, Dr. Bick said. Interpretation of the images was done first without the CEDM images, then with them. The mean age of the women was 55 years.

Although severe adverse reactions to intravenous iodine contrast are rare, at about 1 in 10,000 patients, one woman had a moderate, but not life-threatening reaction to the contrast medium, said Dr. Bick, who disclosed no relevant conflicts of interest. Dr. Felix Diekmann, also of Charité School of Medicine-Berlin, led the study.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Iodine contrast-enhanced digital mammography may be a useful and inexpensive alternative to follow-up magnetic resonance imaging in women with suspicious lesions on mammography, according to data presented at the annual meeting of the Radiological Society of North America.

The use of iodine-based contrast medium as an adjunct to mammography significantly reduced the average number of overlooked malignant lesions from 17 to 11, compared with digital mammography alone in a study of 70 women with 80 suspicious findings. Overlooked lesions were defined as malignant lesions with a Breast Imaging Reporting and Data System score of 3 or lower.

The biggest benefit of contrast-enhanced digital mammography (CEDM) was observed in women with dense breasts, said Dr. Ulrick Bick, department of radiology, Charité School of Medicine-Berlin. In all of the women, sensitivity improved from 43% with standard digital mammography to 62% with CEDM, and from 57% to 64% for women with American College of Radiology (ACR) density I-II breasts, and from 35% to 59% for women with ACR density III-IV breasts. Specificity decreased from 70% to 65%; 72% to 71%; and 69% to 62%, respectively.

“You are [not] going to see additional lesions compared with MRI, but you may have less trouble with false positives,” Dr. Bick said in an interview. “On MRI, you see a lot of small enhancing foci that may not be significant, and that may be different with iodine contrast. [There'll be fewer] false positives.”

In addition, iodine contrast is more widely available and less expensive than MRI. The main application for an iodine contrast-enhanced mammogram would be as an adjunct in cases in which a lesion is difficult to visualize on mammogram, typically because of dense breasts or lesions embedded in dense parenchyma, he said.

A receiver-operator analysis showed that all three independent readers saw an improvement with the addition of CEDM. The increase was significant for two of the three readers.

Of note was that two of the three readers used CEDM only to upgrade lesions to a higher probability of malignancy, whereas the third reader, who saw less benefit from CEDM, used it to downgrade lesions.

“This is something we also learned in a separate-reader study—if you don't see enhancement on CEDM, then you cannot use that to exclude malignancy,” Dr. Bick said. “This is a very important finding.”

Among the 80 suspicious findings at baseline, 50 were benign and 30 were malignant, including 25 invasive cancers and 5 ductal carcinoma in situ cancers. The lesions were fairly large, with an average size of 3.2 cm.

The images were acquired on modified Senographe 2000D (GE Healthcare) full-field digital mammography machine, and obtained before and 60, 120, and 180 seconds after injection of 1 mg/kg of iodine-based contrast medium (Ultravist 370, Schering, Germany). The machine was modified with a copper filter for iodine imaging, and a substraction imaging technique was used to visualize the contrast enhancement, Dr. Bick said. Interpretation of the images was done first without the CEDM images, then with them. The mean age of the women was 55 years.

Although severe adverse reactions to intravenous iodine contrast are rare, at about 1 in 10,000 patients, one woman had a moderate, but not life-threatening reaction to the contrast medium, said Dr. Bick, who disclosed no relevant conflicts of interest. Dr. Felix Diekmann, also of Charité School of Medicine-Berlin, led the study.

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — A strategy of watchful waiting reduced antibiotic use and was well accepted by parents of children diagnosed with acute otitis media in the emergency department in a randomized trial of 223 children.

Previous trials have evaluated a management strategy for otitis media in which the use of antibiotics was optional, but most were conducted in office settings in which parents had an established relationship with their providers.

A more recent study in the emergency department (ED) found a 56% reduction in antibiotic use when parents of children with acute otitis media were given a prescription but asked not to fill it unless the child's condition remained unchanged or worsened in 48 hours (JAMA 2006;296:1235–41).

The current study looked at parental acceptance of such a policy in the ED, Dr. Jennifer Chao said at the annual meeting of the Pediatric Academic Societies.

The American Academy of Family Physicians and American Academy of Pediatrics 2004 practice guidelines suggest minimizing antibiotic side effects by giving parents of select children the option of fighting the infection on their own for 48–72 hours, then starting antibiotics if the symptoms do not improve.

The investigators randomized 232 children, aged 2–12 years, diagnosed with acute otitis media who met AAP criteria for delayed antibiotic treatment to a watchful-waiting strategy that included pain medications and no antibiotic prescription, or to safety net antibiotic protocol (SNAP) that included pain medications and an antibiotic prescription.

Watchful-waiting parents had to return to the ED or to the child's provider if symptoms persisted for 2 or 3 days, whereas SNAP parents had to fill their prescription if symptoms persisted for 2 or 3 days. A research assistant, blinded to group assignment, conducted telephone surveys with parents 7–10 days after the ED visit. One hundred watchful-waiting parents and 106 SNAP parents completed follow-up. The mean age of the children was 5 years.

During the 2–3 day observation period, 87% of the watchful-waiting group adhered to the management protocol and did not use antibiotics, vs. 62% of the SNAP group, Dr. Chao and colleagues of the Jacobi Medical Center, N.Y., reported. During the 7–10-day follow-up period, 81% and 53%, respectively, did not use antibiotics.

Both watchful waiting and SNAP were well accepted by parents, with 91% vs. 95% of parents “very” or “extremely satisfied” with the protocol. The difference was not statistically significant.

Both groups were equally willing to consider observation therapy in the future (65% vs. 62%). “Observation therapy without a prescription substantially improves adherence and reduces antibiotic exposure,” Dr. Chao said.

In a logistic regression analysis, predictors of parental adherence to observation therapy included assignment to therapy, duration of fever before and after the visit, height of fever, and physician predictions of adherence.

No complications were reported. Antibiotics were used in 9 patients who reported fever for more than 4 days and in 16 patients reporting pain longer than 4 days. Data on patients who returned to the ED and/or went to see another provider were not available, said Dr. Chao, who is now with the State University of New York Downstate Medical Center in Brooklyn.

TORONTO — A strategy of watchful waiting reduced antibiotic use and was well accepted by parents of children diagnosed with acute otitis media in the emergency department in a randomized trial of 223 children.

Previous trials have evaluated a management strategy for otitis media in which the use of antibiotics was optional, but most were conducted in office settings in which parents had an established relationship with their providers.

A more recent study in the emergency department (ED) found a 56% reduction in antibiotic use when parents of children with acute otitis media were given a prescription but asked not to fill it unless the child's condition remained unchanged or worsened in 48 hours (JAMA 2006;296:1235–41).

The current study looked at parental acceptance of such a policy in the ED, Dr. Jennifer Chao said at the annual meeting of the Pediatric Academic Societies.

The American Academy of Family Physicians and American Academy of Pediatrics 2004 practice guidelines suggest minimizing antibiotic side effects by giving parents of select children the option of fighting the infection on their own for 48–72 hours, then starting antibiotics if the symptoms do not improve.

The investigators randomized 232 children, aged 2–12 years, diagnosed with acute otitis media who met AAP criteria for delayed antibiotic treatment to a watchful-waiting strategy that included pain medications and no antibiotic prescription, or to safety net antibiotic protocol (SNAP) that included pain medications and an antibiotic prescription.

Watchful-waiting parents had to return to the ED or to the child's provider if symptoms persisted for 2 or 3 days, whereas SNAP parents had to fill their prescription if symptoms persisted for 2 or 3 days. A research assistant, blinded to group assignment, conducted telephone surveys with parents 7–10 days after the ED visit. One hundred watchful-waiting parents and 106 SNAP parents completed follow-up. The mean age of the children was 5 years.

During the 2–3 day observation period, 87% of the watchful-waiting group adhered to the management protocol and did not use antibiotics, vs. 62% of the SNAP group, Dr. Chao and colleagues of the Jacobi Medical Center, N.Y., reported. During the 7–10-day follow-up period, 81% and 53%, respectively, did not use antibiotics.

Both watchful waiting and SNAP were well accepted by parents, with 91% vs. 95% of parents “very” or “extremely satisfied” with the protocol. The difference was not statistically significant.

Both groups were equally willing to consider observation therapy in the future (65% vs. 62%). “Observation therapy without a prescription substantially improves adherence and reduces antibiotic exposure,” Dr. Chao said.

In a logistic regression analysis, predictors of parental adherence to observation therapy included assignment to therapy, duration of fever before and after the visit, height of fever, and physician predictions of adherence.

No complications were reported. Antibiotics were used in 9 patients who reported fever for more than 4 days and in 16 patients reporting pain longer than 4 days. Data on patients who returned to the ED and/or went to see another provider were not available, said Dr. Chao, who is now with the State University of New York Downstate Medical Center in Brooklyn.

TORONTO — A strategy of watchful waiting reduced antibiotic use and was well accepted by parents of children diagnosed with acute otitis media in the emergency department in a randomized trial of 223 children.

Previous trials have evaluated a management strategy for otitis media in which the use of antibiotics was optional, but most were conducted in office settings in which parents had an established relationship with their providers.

A more recent study in the emergency department (ED) found a 56% reduction in antibiotic use when parents of children with acute otitis media were given a prescription but asked not to fill it unless the child's condition remained unchanged or worsened in 48 hours (JAMA 2006;296:1235–41).

The current study looked at parental acceptance of such a policy in the ED, Dr. Jennifer Chao said at the annual meeting of the Pediatric Academic Societies.

The American Academy of Family Physicians and American Academy of Pediatrics 2004 practice guidelines suggest minimizing antibiotic side effects by giving parents of select children the option of fighting the infection on their own for 48–72 hours, then starting antibiotics if the symptoms do not improve.

The investigators randomized 232 children, aged 2–12 years, diagnosed with acute otitis media who met AAP criteria for delayed antibiotic treatment to a watchful-waiting strategy that included pain medications and no antibiotic prescription, or to safety net antibiotic protocol (SNAP) that included pain medications and an antibiotic prescription.

Watchful-waiting parents had to return to the ED or to the child's provider if symptoms persisted for 2 or 3 days, whereas SNAP parents had to fill their prescription if symptoms persisted for 2 or 3 days. A research assistant, blinded to group assignment, conducted telephone surveys with parents 7–10 days after the ED visit. One hundred watchful-waiting parents and 106 SNAP parents completed follow-up. The mean age of the children was 5 years.

During the 2–3 day observation period, 87% of the watchful-waiting group adhered to the management protocol and did not use antibiotics, vs. 62% of the SNAP group, Dr. Chao and colleagues of the Jacobi Medical Center, N.Y., reported. During the 7–10-day follow-up period, 81% and 53%, respectively, did not use antibiotics.

Both watchful waiting and SNAP were well accepted by parents, with 91% vs. 95% of parents “very” or “extremely satisfied” with the protocol. The difference was not statistically significant.

Both groups were equally willing to consider observation therapy in the future (65% vs. 62%). “Observation therapy without a prescription substantially improves adherence and reduces antibiotic exposure,” Dr. Chao said.

In a logistic regression analysis, predictors of parental adherence to observation therapy included assignment to therapy, duration of fever before and after the visit, height of fever, and physician predictions of adherence.

No complications were reported. Antibiotics were used in 9 patients who reported fever for more than 4 days and in 16 patients reporting pain longer than 4 days. Data on patients who returned to the ED and/or went to see another provider were not available, said Dr. Chao, who is now with the State University of New York Downstate Medical Center in Brooklyn.