Michele G. Sullivan

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of the 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446-51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed.

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview.

Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered refusers if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; among the controls, only 0.7% had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts.

Vaccine refusers were 23 times more likely to contract Bordetella pertussis. ©CDC

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of the 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446-51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed.

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview.

Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered refusers if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; among the controls, only 0.7% had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts.

Vaccine refusers were 23 times more likely to contract Bordetella pertussis. ©CDC

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of the 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446-51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed.

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview.

Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered refusers if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; among the controls, only 0.7% had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts.

Vaccine refusers were 23 times more likely to contract Bordetella pertussis. ©CDC

A modified-release formulation of prednisone reduced morning stiffness duration in patients with rheumatoid arthritis, according to data presented at the annual European Congress of Rheumatology.

The new formulation is designed to be taken at bedtime. The medication is released about 4 hours after ingestion, with the goal of adapting glucocorticoid drug release to the circadian rhythms of endogenous cortisol and symptoms of the disease, both of which have their peaks during the early morning hours. It has been theorized that morning glucocorticoid dosing only inadequately controls the circadian rhythm of RA symptoms in these patients, Prof. Frank Buttgereit, of Charité Medical University of Berlin, said in an interview.

“It's well known that symptoms of rheumatoid arthritis follow circadian rhythms and are typically most prominent in the early morning hours,” he said. “Therefore, the timing of systemic glucocorticoid therapy may be important with respect to the natural secretion of endogenous glucocorticoids as well as the control of symptoms.”

Findings from earlier research conducted by Prof. Buttgereit and his associates involved a 3-month randomized, controlled trial of 288 patients with long-standing active rheumatoid arthritis (Lancet 2008;371:205-14).

The data he presented at EULAR concerned 219 patients who completed a new 9-month follow-on open-label trial of the same group, during which all patients took the modified-release formulation.

At baseline, the patients' mean age was 55 years; their mean duration of disease was 10 years. Patients who were randomized to the active group took a placebo tablet in the morning and the study drug in the evening. The comparator group took immediate-release prednisone in the morning and placebo in the evening. The prednisone dose was individually titrated (range, 3-10 mg/day).

The mean relative reduction of morning stiffness duration was significantly higher in the modified-release group than in the immediate-release group (23% vs. 0.4%). Patients taking the modified-release drug had a significantly greater decrease in duration of morning joint stiffness than did those taking the immediate-release tablet (44 vs. 23 fewer minutes of morning stiffness). Median levels of interleukin-6 were also reduced in the modified-release group compared with the immediate-release group (29% vs. 0%).

Adverse events led to premature discontinuation of the study drugs in 8% of patients in the modified-release group and 7% of those in the immediate-release group. The frequency of serious adverse events was low and similar in both groups (3% vs. 2%).

The combined results of the randomized and open-label trials, showed that in both groups, morning stiffness duration remained similarly low over the entire study duration, he said. At 12 months, the reduction was somewhat greater in the group that had taken the modified-release formulation during both trials (55%) than among those who took the immediate-release during the first trial and the modified-release during the follow-on study (45%).

Among his expected conclusions is that “bedtime administration of prednisone via the new modified-release tablet provides significantly greater efficacy for at least 12 months over conventional immediate-release prednisone, due to prednisone release which occurs prior to the circadian flare-up of IL-6 synthesis and inflammatory activity.”

The study was sponsored by Merck Pharma GmbH and Nitec Pharma AG. Prof. Buttgereit and some of the coauthors said they had received consulting and grant funding from the companies.

A modified-release formulation of prednisone reduced morning stiffness duration in patients with rheumatoid arthritis, according to data presented at the annual European Congress of Rheumatology.

The new formulation is designed to be taken at bedtime. The medication is released about 4 hours after ingestion, with the goal of adapting glucocorticoid drug release to the circadian rhythms of endogenous cortisol and symptoms of the disease, both of which have their peaks during the early morning hours. It has been theorized that morning glucocorticoid dosing only inadequately controls the circadian rhythm of RA symptoms in these patients, Prof. Frank Buttgereit, of Charité Medical University of Berlin, said in an interview.

“It's well known that symptoms of rheumatoid arthritis follow circadian rhythms and are typically most prominent in the early morning hours,” he said. “Therefore, the timing of systemic glucocorticoid therapy may be important with respect to the natural secretion of endogenous glucocorticoids as well as the control of symptoms.”

Findings from earlier research conducted by Prof. Buttgereit and his associates involved a 3-month randomized, controlled trial of 288 patients with long-standing active rheumatoid arthritis (Lancet 2008;371:205-14).

The data he presented at EULAR concerned 219 patients who completed a new 9-month follow-on open-label trial of the same group, during which all patients took the modified-release formulation.

At baseline, the patients' mean age was 55 years; their mean duration of disease was 10 years. Patients who were randomized to the active group took a placebo tablet in the morning and the study drug in the evening. The comparator group took immediate-release prednisone in the morning and placebo in the evening. The prednisone dose was individually titrated (range, 3-10 mg/day).

The mean relative reduction of morning stiffness duration was significantly higher in the modified-release group than in the immediate-release group (23% vs. 0.4%). Patients taking the modified-release drug had a significantly greater decrease in duration of morning joint stiffness than did those taking the immediate-release tablet (44 vs. 23 fewer minutes of morning stiffness). Median levels of interleukin-6 were also reduced in the modified-release group compared with the immediate-release group (29% vs. 0%).

Adverse events led to premature discontinuation of the study drugs in 8% of patients in the modified-release group and 7% of those in the immediate-release group. The frequency of serious adverse events was low and similar in both groups (3% vs. 2%).

The combined results of the randomized and open-label trials, showed that in both groups, morning stiffness duration remained similarly low over the entire study duration, he said. At 12 months, the reduction was somewhat greater in the group that had taken the modified-release formulation during both trials (55%) than among those who took the immediate-release during the first trial and the modified-release during the follow-on study (45%).

Among his expected conclusions is that “bedtime administration of prednisone via the new modified-release tablet provides significantly greater efficacy for at least 12 months over conventional immediate-release prednisone, due to prednisone release which occurs prior to the circadian flare-up of IL-6 synthesis and inflammatory activity.”

The study was sponsored by Merck Pharma GmbH and Nitec Pharma AG. Prof. Buttgereit and some of the coauthors said they had received consulting and grant funding from the companies.

A modified-release formulation of prednisone reduced morning stiffness duration in patients with rheumatoid arthritis, according to data presented at the annual European Congress of Rheumatology.

The new formulation is designed to be taken at bedtime. The medication is released about 4 hours after ingestion, with the goal of adapting glucocorticoid drug release to the circadian rhythms of endogenous cortisol and symptoms of the disease, both of which have their peaks during the early morning hours. It has been theorized that morning glucocorticoid dosing only inadequately controls the circadian rhythm of RA symptoms in these patients, Prof. Frank Buttgereit, of Charité Medical University of Berlin, said in an interview.

“It's well known that symptoms of rheumatoid arthritis follow circadian rhythms and are typically most prominent in the early morning hours,” he said. “Therefore, the timing of systemic glucocorticoid therapy may be important with respect to the natural secretion of endogenous glucocorticoids as well as the control of symptoms.”

Findings from earlier research conducted by Prof. Buttgereit and his associates involved a 3-month randomized, controlled trial of 288 patients with long-standing active rheumatoid arthritis (Lancet 2008;371:205-14).

The data he presented at EULAR concerned 219 patients who completed a new 9-month follow-on open-label trial of the same group, during which all patients took the modified-release formulation.

At baseline, the patients' mean age was 55 years; their mean duration of disease was 10 years. Patients who were randomized to the active group took a placebo tablet in the morning and the study drug in the evening. The comparator group took immediate-release prednisone in the morning and placebo in the evening. The prednisone dose was individually titrated (range, 3-10 mg/day).

The mean relative reduction of morning stiffness duration was significantly higher in the modified-release group than in the immediate-release group (23% vs. 0.4%). Patients taking the modified-release drug had a significantly greater decrease in duration of morning joint stiffness than did those taking the immediate-release tablet (44 vs. 23 fewer minutes of morning stiffness). Median levels of interleukin-6 were also reduced in the modified-release group compared with the immediate-release group (29% vs. 0%).

Adverse events led to premature discontinuation of the study drugs in 8% of patients in the modified-release group and 7% of those in the immediate-release group. The frequency of serious adverse events was low and similar in both groups (3% vs. 2%).

The combined results of the randomized and open-label trials, showed that in both groups, morning stiffness duration remained similarly low over the entire study duration, he said. At 12 months, the reduction was somewhat greater in the group that had taken the modified-release formulation during both trials (55%) than among those who took the immediate-release during the first trial and the modified-release during the follow-on study (45%).

Among his expected conclusions is that “bedtime administration of prednisone via the new modified-release tablet provides significantly greater efficacy for at least 12 months over conventional immediate-release prednisone, due to prednisone release which occurs prior to the circadian flare-up of IL-6 synthesis and inflammatory activity.”

The study was sponsored by Merck Pharma GmbH and Nitec Pharma AG. Prof. Buttgereit and some of the coauthors said they had received consulting and grant funding from the companies.

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA has requested that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

“The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries,” the FDA said in a public information statement. “These are preventable by having Gardasil recipients remain seated or lying down for 15 minutes following vaccination and closely watching them for the following warning signs and symptoms: paleness, sweating, dizziness, ringing in ears or vision changes, which generally occur before fainting.”

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. “If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain.”

Syncope has been listed on the Gardasil label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning.

Fainting doesn't appear to be unique to Gardasil, the statement added. “Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain.”

The fact sheet did not give details of the injuries associated with all these events. However, 70 episodes of syncope in U.S. patients were reported in the May 2, 2008, issue of the Morbidity and Mortality Weekly Report (2008; 57:457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious; 38 occurred on the same day as vaccination and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States. Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

However, the vaccine is still considered a safe and effective one, the FDA said in the public information statement. “Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, health care providers, and the public, and needed action will be taken to ensure the public's health and safety.”

Information regarding adverse events that are associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA has requested that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

“The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries,” the FDA said in a public information statement. “These are preventable by having Gardasil recipients remain seated or lying down for 15 minutes following vaccination and closely watching them for the following warning signs and symptoms: paleness, sweating, dizziness, ringing in ears or vision changes, which generally occur before fainting.”

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. “If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain.”

Syncope has been listed on the Gardasil label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning.

Fainting doesn't appear to be unique to Gardasil, the statement added. “Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain.”

The fact sheet did not give details of the injuries associated with all these events. However, 70 episodes of syncope in U.S. patients were reported in the May 2, 2008, issue of the Morbidity and Mortality Weekly Report (2008; 57:457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious; 38 occurred on the same day as vaccination and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States. Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

However, the vaccine is still considered a safe and effective one, the FDA said in the public information statement. “Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, health care providers, and the public, and needed action will be taken to ensure the public's health and safety.”

Information regarding adverse events that are associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA has requested that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

“The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries,” the FDA said in a public information statement. “These are preventable by having Gardasil recipients remain seated or lying down for 15 minutes following vaccination and closely watching them for the following warning signs and symptoms: paleness, sweating, dizziness, ringing in ears or vision changes, which generally occur before fainting.”

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. “If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain.”

Syncope has been listed on the Gardasil label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning.

Fainting doesn't appear to be unique to Gardasil, the statement added. “Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain.”

The fact sheet did not give details of the injuries associated with all these events. However, 70 episodes of syncope in U.S. patients were reported in the May 2, 2008, issue of the Morbidity and Mortality Weekly Report (2008; 57:457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious; 38 occurred on the same day as vaccination and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States. Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

However, the vaccine is still considered a safe and effective one, the FDA said in the public information statement. “Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, health care providers, and the public, and needed action will be taken to ensure the public's health and safety.”

Information regarding adverse events that are associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

CHICAGO — Radiofrequency ablation appears to provide a durable, safe, and complete eradication of dysplastic Barrett's esophagus in most patients.

Two years after undergoing radiofrequency ablation (RFA), 96% of patients with complete eradication of intestinal dysplasia at 1 year were still free of abnormal cells, Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Only 2 of the 50 patients analyzed experienced disease recurrence; both had relatively long lengths of high-grade dysplasia at baseline, which recurred as short lengths of low-grade dysplasia 2 years later, said Dr. Shaheen of the University of North Carolina at Chapel Hill.

Dr. Shaheen presented 2-year follow-up data from the Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia) trial. The study randomized 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to RFA or a sham procedure. Previously, 1-year data showed that the procedure completely eradicated dysplasia in 81% of those with high-grade dysplasia and in 90% of those with low-grade dysplasia. Overall, 77% of the ablation group had complete eradication (N. Engl. J. Med. 2009;360:2277-88).

Regardless of dysplasia level, the 84 patients who received ablation were significantly more likely than the 43 in the control group to have complete eradication of dysplasia, Dr. Shaheen reported.

The sham procedure was associated with eradication of intestinal dysplasia in 23% of patients who had low-grade dysplasia and 19% of those who had high-grade dysplasia. The patients in the control group were much more likely to show disease progression at 1 year (16%) than were the patients in the ablation group (4%), he said.

Among patients with low-grade dysplasia, 98% of the biopsy samples in the ablation group were free of intestinal metaplasia at 1 year, compared with 57% of biopsies in the control group. Similarly, among patients with high-grade dysplasia, 98% of the specimens from patients who underwent ablation were free of intestinal metaplasia at 1 year, compared with 59% of samples from control patients.

Patients who received the sham procedure were offered ablation after the first year of follow-up; all accepted. Currently, 119 patients have been treated.

The follow-up study reported at the meeting included 50 patients with complete eradication of dysplasia at 1 year and 2 full years of follow-up data. Low-grade dysplasia was present at baseline in 32 patients, high-grade in 18 patients. The mean age at baseline was 65 years; the mean length of Barrett's esophagus at baseline was 4 cm.

The procedure was considered very safe, Dr. Shaheen said. Of the four serious adverse events, three occurred in the first year (two cases of chest pain requiring admission; one gastrointestinal hemorrhage in a patient on antiplatelet therapy). During the second year, one more patient required admission for evaluation of chest pain.

Esophageal stricture developed in five patients during the first year and in four others during the second year. Six of the strictures developed after circumferential ablation and three after focal ablation. “Of note, three of these patients had a stricture prior to the procedure,” he said. All strictures were easily resolved with a median of 1.5 dilations.

In the overall intent-to-treat analysis, 92% of patients who had complete response at 1 year maintained complete response at 2 years. The rate was higher, at 96%, in the per-protocol analysis.

Among patients with high-grade dysplasia at baseline, 83% retained complete response (complete eradication of intestinal metaplasia) at 2 years in the intent-to-treat analysis; 88% did so in the per-protocol analysis. Among patients with low-grade dysplasia at baseline, 97% retained complete response in the intent-to-treat analysis, and 100% in the per-protocol analysis.

Only two patients showed disease progression, Dr. Shaheen reported. “One patient had a 6-cm length of high-grade dysplasia at baseline, and a 1-cm section of low-grade dysplasia at 2 years. The other had a 5-cm section of high-grade dysplasia at baseline, and a 0.5-cm length of low-grade dysplasia at the follow-up.”

Dr. Shaheen disclosed that he has received research grants from BÂRRX Medical, which sponsored the study and manufactures the endoscopic ablation system used in it. He has also received research funding and honoraria from numerous pharmaceutical companies.

Mary Ann Moon contributed to this report.

At 2 years, 96% of patients with a complete response to RFA at 1 year were still free of abnormal cells. DR. SHAHEEN

CHICAGO — Radiofrequency ablation appears to provide a durable, safe, and complete eradication of dysplastic Barrett's esophagus in most patients.

Two years after undergoing radiofrequency ablation (RFA), 96% of patients with complete eradication of intestinal dysplasia at 1 year were still free of abnormal cells, Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Only 2 of the 50 patients analyzed experienced disease recurrence; both had relatively long lengths of high-grade dysplasia at baseline, which recurred as short lengths of low-grade dysplasia 2 years later, said Dr. Shaheen of the University of North Carolina at Chapel Hill.

Dr. Shaheen presented 2-year follow-up data from the Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia) trial. The study randomized 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to RFA or a sham procedure. Previously, 1-year data showed that the procedure completely eradicated dysplasia in 81% of those with high-grade dysplasia and in 90% of those with low-grade dysplasia. Overall, 77% of the ablation group had complete eradication (N. Engl. J. Med. 2009;360:2277-88).

Regardless of dysplasia level, the 84 patients who received ablation were significantly more likely than the 43 in the control group to have complete eradication of dysplasia, Dr. Shaheen reported.

The sham procedure was associated with eradication of intestinal dysplasia in 23% of patients who had low-grade dysplasia and 19% of those who had high-grade dysplasia. The patients in the control group were much more likely to show disease progression at 1 year (16%) than were the patients in the ablation group (4%), he said.

Among patients with low-grade dysplasia, 98% of the biopsy samples in the ablation group were free of intestinal metaplasia at 1 year, compared with 57% of biopsies in the control group. Similarly, among patients with high-grade dysplasia, 98% of the specimens from patients who underwent ablation were free of intestinal metaplasia at 1 year, compared with 59% of samples from control patients.

Patients who received the sham procedure were offered ablation after the first year of follow-up; all accepted. Currently, 119 patients have been treated.

The follow-up study reported at the meeting included 50 patients with complete eradication of dysplasia at 1 year and 2 full years of follow-up data. Low-grade dysplasia was present at baseline in 32 patients, high-grade in 18 patients. The mean age at baseline was 65 years; the mean length of Barrett's esophagus at baseline was 4 cm.

The procedure was considered very safe, Dr. Shaheen said. Of the four serious adverse events, three occurred in the first year (two cases of chest pain requiring admission; one gastrointestinal hemorrhage in a patient on antiplatelet therapy). During the second year, one more patient required admission for evaluation of chest pain.

Esophageal stricture developed in five patients during the first year and in four others during the second year. Six of the strictures developed after circumferential ablation and three after focal ablation. “Of note, three of these patients had a stricture prior to the procedure,” he said. All strictures were easily resolved with a median of 1.5 dilations.

In the overall intent-to-treat analysis, 92% of patients who had complete response at 1 year maintained complete response at 2 years. The rate was higher, at 96%, in the per-protocol analysis.

Among patients with high-grade dysplasia at baseline, 83% retained complete response (complete eradication of intestinal metaplasia) at 2 years in the intent-to-treat analysis; 88% did so in the per-protocol analysis. Among patients with low-grade dysplasia at baseline, 97% retained complete response in the intent-to-treat analysis, and 100% in the per-protocol analysis.

Only two patients showed disease progression, Dr. Shaheen reported. “One patient had a 6-cm length of high-grade dysplasia at baseline, and a 1-cm section of low-grade dysplasia at 2 years. The other had a 5-cm section of high-grade dysplasia at baseline, and a 0.5-cm length of low-grade dysplasia at the follow-up.”

Dr. Shaheen disclosed that he has received research grants from BÂRRX Medical, which sponsored the study and manufactures the endoscopic ablation system used in it. He has also received research funding and honoraria from numerous pharmaceutical companies.

Mary Ann Moon contributed to this report.

At 2 years, 96% of patients with a complete response to RFA at 1 year were still free of abnormal cells. DR. SHAHEEN

CHICAGO — Radiofrequency ablation appears to provide a durable, safe, and complete eradication of dysplastic Barrett's esophagus in most patients.

Two years after undergoing radiofrequency ablation (RFA), 96% of patients with complete eradication of intestinal dysplasia at 1 year were still free of abnormal cells, Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Only 2 of the 50 patients analyzed experienced disease recurrence; both had relatively long lengths of high-grade dysplasia at baseline, which recurred as short lengths of low-grade dysplasia 2 years later, said Dr. Shaheen of the University of North Carolina at Chapel Hill.

Dr. Shaheen presented 2-year follow-up data from the Ablation of Intestinal Metaplasia Containing Dysplasia (AIM Dysplasia) trial. The study randomized 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to RFA or a sham procedure. Previously, 1-year data showed that the procedure completely eradicated dysplasia in 81% of those with high-grade dysplasia and in 90% of those with low-grade dysplasia. Overall, 77% of the ablation group had complete eradication (N. Engl. J. Med. 2009;360:2277-88).

Regardless of dysplasia level, the 84 patients who received ablation were significantly more likely than the 43 in the control group to have complete eradication of dysplasia, Dr. Shaheen reported.

The sham procedure was associated with eradication of intestinal dysplasia in 23% of patients who had low-grade dysplasia and 19% of those who had high-grade dysplasia. The patients in the control group were much more likely to show disease progression at 1 year (16%) than were the patients in the ablation group (4%), he said.

Among patients with low-grade dysplasia, 98% of the biopsy samples in the ablation group were free of intestinal metaplasia at 1 year, compared with 57% of biopsies in the control group. Similarly, among patients with high-grade dysplasia, 98% of the specimens from patients who underwent ablation were free of intestinal metaplasia at 1 year, compared with 59% of samples from control patients.

Patients who received the sham procedure were offered ablation after the first year of follow-up; all accepted. Currently, 119 patients have been treated.

The follow-up study reported at the meeting included 50 patients with complete eradication of dysplasia at 1 year and 2 full years of follow-up data. Low-grade dysplasia was present at baseline in 32 patients, high-grade in 18 patients. The mean age at baseline was 65 years; the mean length of Barrett's esophagus at baseline was 4 cm.

The procedure was considered very safe, Dr. Shaheen said. Of the four serious adverse events, three occurred in the first year (two cases of chest pain requiring admission; one gastrointestinal hemorrhage in a patient on antiplatelet therapy). During the second year, one more patient required admission for evaluation of chest pain.

Esophageal stricture developed in five patients during the first year and in four others during the second year. Six of the strictures developed after circumferential ablation and three after focal ablation. “Of note, three of these patients had a stricture prior to the procedure,” he said. All strictures were easily resolved with a median of 1.5 dilations.

In the overall intent-to-treat analysis, 92% of patients who had complete response at 1 year maintained complete response at 2 years. The rate was higher, at 96%, in the per-protocol analysis.

Among patients with high-grade dysplasia at baseline, 83% retained complete response (complete eradication of intestinal metaplasia) at 2 years in the intent-to-treat analysis; 88% did so in the per-protocol analysis. Among patients with low-grade dysplasia at baseline, 97% retained complete response in the intent-to-treat analysis, and 100% in the per-protocol analysis.

Only two patients showed disease progression, Dr. Shaheen reported. “One patient had a 6-cm length of high-grade dysplasia at baseline, and a 1-cm section of low-grade dysplasia at 2 years. The other had a 5-cm section of high-grade dysplasia at baseline, and a 0.5-cm length of low-grade dysplasia at the follow-up.”

Dr. Shaheen disclosed that he has received research grants from BÂRRX Medical, which sponsored the study and manufactures the endoscopic ablation system used in it. He has also received research funding and honoraria from numerous pharmaceutical companies.

Mary Ann Moon contributed to this report.

At 2 years, 96% of patients with a complete response to RFA at 1 year were still free of abnormal cells. DR. SHAHEEN

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in the national CESAME (Cancers et Sur-Risque Associé aux Maladies Inflammatoires Chroniques Intestinales en France) study. CESAME is a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007. Dr. Seksik's analysis included follow-up data from 85% of the cohort.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among patients with long-standing extensive colitis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% methotrexate, and 5% a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of colorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five colorectal cancers and one case of high-grade dysplasia.

On multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive colitis, the presence of extensive colitis significantly increased the risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thiopurine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thiopurine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.” Dr. Seksik said that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%. DR. SEKSIK

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in the national CESAME (Cancers et Sur-Risque Associé aux Maladies Inflammatoires Chroniques Intestinales en France) study. CESAME is a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007. Dr. Seksik's analysis included follow-up data from 85% of the cohort.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among patients with long-standing extensive colitis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% methotrexate, and 5% a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of colorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five colorectal cancers and one case of high-grade dysplasia.

On multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive colitis, the presence of extensive colitis significantly increased the risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thiopurine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thiopurine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.” Dr. Seksik said that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%. DR. SEKSIK

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in the national CESAME (Cancers et Sur-Risque Associé aux Maladies Inflammatoires Chroniques Intestinales en France) study. CESAME is a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007. Dr. Seksik's analysis included follow-up data from 85% of the cohort.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among patients with long-standing extensive colitis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% methotrexate, and 5% a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of colorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five colorectal cancers and one case of high-grade dysplasia.

On multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive colitis, the presence of extensive colitis significantly increased the risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thiopurine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thiopurine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.” Dr. Seksik said that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%. DR. SEKSIK

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA requested in June that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

"The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries," the FDA said in a public information statement.

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. "If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain."

Syncope has been listed on the label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning. Fainting doesn't appear to be unique to Gardasil, the statement added. "Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain."

The fact sheet did not give details of the injuries associated with the events. However, 70 episodes of syncope in U.S. patients were reported (MMWR 2008;57;457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious, 38 occurred on the same day as vaccination, and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States.

Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

Serious adverse events include Guillain-Barré Syndrome (GBS), transverse myelitis, and blood clots. Additionally, as of May 1, the FDA has received 39 reports of death among females who have received the vaccine. Twenty-six of these reports have been confirmed, six are still under investigation, and seven are unconfirmed. According to a fact sheet on the VAERS Web site, "In the 26 reports confirmed, there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine."

The VAERSfact sheet did not give details of all these deaths. However, details of deaths that had occurred from June 30, 2006, to August 31, 2008, were reported during an October 2008 postlicensure safety update held by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The committee reviewed 27 deaths following Gardasil vaccination; 17 of those had been confirmed. Deaths occurred in females aged 12–26 years with no discernible pattern to age or time since vaccine administration. Six occurred within 1 week of vaccination, five within 2–3 weeks, two within 3–9 weeks, and two within 9–17 weeks. One death occurred 288 days after vaccination, and one case had an unknown onset interval.

Other serious adverse events detailed during the committee meeting were syncope (70), venous thromboembolism (41), GBS (52), and transverse myelitis (10).

The vaccine is considered safe and effective, the FDA said in the public information statement. "Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, healthcare providers, and the public, and needed action will be taken to ensure the public's health and safety."

Information regarding adverse events associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA requested in June that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

"The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries," the FDA said in a public information statement.

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. "If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain."

Syncope has been listed on the label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning. Fainting doesn't appear to be unique to Gardasil, the statement added. "Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain."

The fact sheet did not give details of the injuries associated with the events. However, 70 episodes of syncope in U.S. patients were reported (MMWR 2008;57;457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious, 38 occurred on the same day as vaccination, and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States.

Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

Serious adverse events include Guillain-Barré Syndrome (GBS), transverse myelitis, and blood clots. Additionally, as of May 1, the FDA has received 39 reports of death among females who have received the vaccine. Twenty-six of these reports have been confirmed, six are still under investigation, and seven are unconfirmed. According to a fact sheet on the VAERS Web site, "In the 26 reports confirmed, there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine."

The VAERSfact sheet did not give details of all these deaths. However, details of deaths that had occurred from June 30, 2006, to August 31, 2008, were reported during an October 2008 postlicensure safety update held by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The committee reviewed 27 deaths following Gardasil vaccination; 17 of those had been confirmed. Deaths occurred in females aged 12–26 years with no discernible pattern to age or time since vaccine administration. Six occurred within 1 week of vaccination, five within 2–3 weeks, two within 3–9 weeks, and two within 9–17 weeks. One death occurred 288 days after vaccination, and one case had an unknown onset interval.

Other serious adverse events detailed during the committee meeting were syncope (70), venous thromboembolism (41), GBS (52), and transverse myelitis (10).

The vaccine is considered safe and effective, the FDA said in the public information statement. "Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, healthcare providers, and the public, and needed action will be taken to ensure the public's health and safety."

Information regarding adverse events associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA requested in June that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

"The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries," the FDA said in a public information statement.

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. "If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain."

Syncope has been listed on the label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning. Fainting doesn't appear to be unique to Gardasil, the statement added. "Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain."

The fact sheet did not give details of the injuries associated with the events. However, 70 episodes of syncope in U.S. patients were reported (MMWR 2008;57;457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious, 38 occurred on the same day as vaccination, and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States.

Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

Serious adverse events include Guillain-Barré Syndrome (GBS), transverse myelitis, and blood clots. Additionally, as of May 1, the FDA has received 39 reports of death among females who have received the vaccine. Twenty-six of these reports have been confirmed, six are still under investigation, and seven are unconfirmed. According to a fact sheet on the VAERS Web site, "In the 26 reports confirmed, there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine."

The VAERSfact sheet did not give details of all these deaths. However, details of deaths that had occurred from June 30, 2006, to August 31, 2008, were reported during an October 2008 postlicensure safety update held by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The committee reviewed 27 deaths following Gardasil vaccination; 17 of those had been confirmed. Deaths occurred in females aged 12–26 years with no discernible pattern to age or time since vaccine administration. Six occurred within 1 week of vaccination, five within 2–3 weeks, two within 3–9 weeks, and two within 9–17 weeks. One death occurred 288 days after vaccination, and one case had an unknown onset interval.

Other serious adverse events detailed during the committee meeting were syncope (70), venous thromboembolism (41), GBS (52), and transverse myelitis (10).

The vaccine is considered safe and effective, the FDA said in the public information statement. "Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, healthcare providers, and the public, and needed action will be taken to ensure the public's health and safety."

Information regarding adverse events associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

While advances in technology have made lasers more effective as a treatment for spider veins, sclerotherapy remains the standard for treatment, according to Dr. Margaret W. Mann.

While there have been significant advances in laser technology that make them an option for some spider veins, most telangiectases respond best to the more traditional treatment, said Dr. Mann, codirector of the dermatologic surgery and laser center at the University of California, Irvine.

"The majority of the time, I tend to reserve lasers for treating spider veins under a few circumstances," Dr. Mann said in an interview. They are best used for superficial vessels with a diameter of 1 mm or less, especially isolated telangiectases or those around the ankles. Patients with telangiectatic matting may also be candidates for laser treatment. Lasers might also be considered for a patient with needle phobia, or someone who has had a poor response to prior sclerotherapy, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). "Outside of those circumstances, I tend to use sclerotherapy, which provides more reproducible results with less discomfort and fewer complications."

Different laser types have specific applications when treating spider veins. The potassium-titanyl-phosphate (KTP) and pulsed dye lasers are usually reserved for small vessels with a diameter of up to 1.5 mm. Melanin tends to absorb the energy from these lasers, which can result in hyperpigmentation.

"The majority of the time, I use the 1064-nm Nd:YAG, because it has a lower risk of pigmentary changes and because the advances in cooling devices associated with the Nd:YAG make overheating less likely," Dr. Mann said.

In contrast to telangiectases on the face, which are best treated with lasers, spider veins on the legs do not uniformly respond to lasers. The homogenous nature of facial telangiectases, both in diameter and depth, makes them easier targets than leg veins. "Telangiectases in the legs are a more heterogenous group; they tend to be different sizes and different depths, so it is harder to uniformly target them than it is the facial vessels."

She recommended an ultrasound evaluation for patients who may have more complicated vessel disease, including those with vessels larger than 5 mm in diameter, palpable varicosities, or classic corona phlebectasia—a clustering of spider veins along the medial malleolus.

Patients who have not responded to multiple sessions with sclerotherapy or lasers should undergo an ultrasound evaluation. "These are all indications of larger vessel disease, such as greater saphenous vein insufficiency." If the ultrasound confirms these findings, treatment with endovenous ablation or microphlebectomy should precede any further sclerotherapy or laser treatments.

Endovenous ablation can be performed in the office with tumescent anesthesia, she said. It requires only a small incision in which a laser fiber is threaded under ultrasound guidance within the vein. The laser is activated and withdrawn, which gently heats the lining of the vein and seals it shut.

Ambulatory microphlebectomy is also a safe, effective option for isolated varicosities. The procedure involves making multiple tiny incisions (1–3 mm) through which the varicose veins are removed. A compression dressing is necessary for 24 hours after the procedure, after which the patient can resume normal activity while wearing compression hose for 3 weeks.

Dr. Mann reported no financial conflicts regarding her presentation.

SDEF and this news organization are owned by Elsevier.

Sclerotherapy 'provides more reproducible results withless discomfort and fewer complications.' DR. MANN

While advances in technology have made lasers more effective as a treatment for spider veins, sclerotherapy remains the standard for treatment, according to Dr. Margaret W. Mann.

While there have been significant advances in laser technology that make them an option for some spider veins, most telangiectases respond best to the more traditional treatment, said Dr. Mann, codirector of the dermatologic surgery and laser center at the University of California, Irvine.

"The majority of the time, I tend to reserve lasers for treating spider veins under a few circumstances," Dr. Mann said in an interview. They are best used for superficial vessels with a diameter of 1 mm or less, especially isolated telangiectases or those around the ankles. Patients with telangiectatic matting may also be candidates for laser treatment. Lasers might also be considered for a patient with needle phobia, or someone who has had a poor response to prior sclerotherapy, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). "Outside of those circumstances, I tend to use sclerotherapy, which provides more reproducible results with less discomfort and fewer complications."

Different laser types have specific applications when treating spider veins. The potassium-titanyl-phosphate (KTP) and pulsed dye lasers are usually reserved for small vessels with a diameter of up to 1.5 mm. Melanin tends to absorb the energy from these lasers, which can result in hyperpigmentation.

"The majority of the time, I use the 1064-nm Nd:YAG, because it has a lower risk of pigmentary changes and because the advances in cooling devices associated with the Nd:YAG make overheating less likely," Dr. Mann said.

In contrast to telangiectases on the face, which are best treated with lasers, spider veins on the legs do not uniformly respond to lasers. The homogenous nature of facial telangiectases, both in diameter and depth, makes them easier targets than leg veins. "Telangiectases in the legs are a more heterogenous group; they tend to be different sizes and different depths, so it is harder to uniformly target them than it is the facial vessels."

She recommended an ultrasound evaluation for patients who may have more complicated vessel disease, including those with vessels larger than 5 mm in diameter, palpable varicosities, or classic corona phlebectasia—a clustering of spider veins along the medial malleolus.

Patients who have not responded to multiple sessions with sclerotherapy or lasers should undergo an ultrasound evaluation. "These are all indications of larger vessel disease, such as greater saphenous vein insufficiency." If the ultrasound confirms these findings, treatment with endovenous ablation or microphlebectomy should precede any further sclerotherapy or laser treatments.

Endovenous ablation can be performed in the office with tumescent anesthesia, she said. It requires only a small incision in which a laser fiber is threaded under ultrasound guidance within the vein. The laser is activated and withdrawn, which gently heats the lining of the vein and seals it shut.

Ambulatory microphlebectomy is also a safe, effective option for isolated varicosities. The procedure involves making multiple tiny incisions (1–3 mm) through which the varicose veins are removed. A compression dressing is necessary for 24 hours after the procedure, after which the patient can resume normal activity while wearing compression hose for 3 weeks.

Dr. Mann reported no financial conflicts regarding her presentation.

SDEF and this news organization are owned by Elsevier.

Sclerotherapy 'provides more reproducible results withless discomfort and fewer complications.' DR. MANN

While advances in technology have made lasers more effective as a treatment for spider veins, sclerotherapy remains the standard for treatment, according to Dr. Margaret W. Mann.

While there have been significant advances in laser technology that make them an option for some spider veins, most telangiectases respond best to the more traditional treatment, said Dr. Mann, codirector of the dermatologic surgery and laser center at the University of California, Irvine.

"The majority of the time, I tend to reserve lasers for treating spider veins under a few circumstances," Dr. Mann said in an interview. They are best used for superficial vessels with a diameter of 1 mm or less, especially isolated telangiectases or those around the ankles. Patients with telangiectatic matting may also be candidates for laser treatment. Lasers might also be considered for a patient with needle phobia, or someone who has had a poor response to prior sclerotherapy, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). "Outside of those circumstances, I tend to use sclerotherapy, which provides more reproducible results with less discomfort and fewer complications."

Different laser types have specific applications when treating spider veins. The potassium-titanyl-phosphate (KTP) and pulsed dye lasers are usually reserved for small vessels with a diameter of up to 1.5 mm. Melanin tends to absorb the energy from these lasers, which can result in hyperpigmentation.

"The majority of the time, I use the 1064-nm Nd:YAG, because it has a lower risk of pigmentary changes and because the advances in cooling devices associated with the Nd:YAG make overheating less likely," Dr. Mann said.

In contrast to telangiectases on the face, which are best treated with lasers, spider veins on the legs do not uniformly respond to lasers. The homogenous nature of facial telangiectases, both in diameter and depth, makes them easier targets than leg veins. "Telangiectases in the legs are a more heterogenous group; they tend to be different sizes and different depths, so it is harder to uniformly target them than it is the facial vessels."

She recommended an ultrasound evaluation for patients who may have more complicated vessel disease, including those with vessels larger than 5 mm in diameter, palpable varicosities, or classic corona phlebectasia—a clustering of spider veins along the medial malleolus.

Patients who have not responded to multiple sessions with sclerotherapy or lasers should undergo an ultrasound evaluation. "These are all indications of larger vessel disease, such as greater saphenous vein insufficiency." If the ultrasound confirms these findings, treatment with endovenous ablation or microphlebectomy should precede any further sclerotherapy or laser treatments.

Endovenous ablation can be performed in the office with tumescent anesthesia, she said. It requires only a small incision in which a laser fiber is threaded under ultrasound guidance within the vein. The laser is activated and withdrawn, which gently heats the lining of the vein and seals it shut.

Ambulatory microphlebectomy is also a safe, effective option for isolated varicosities. The procedure involves making multiple tiny incisions (1–3 mm) through which the varicose veins are removed. A compression dressing is necessary for 24 hours after the procedure, after which the patient can resume normal activity while wearing compression hose for 3 weeks.

Dr. Mann reported no financial conflicts regarding her presentation.

SDEF and this news organization are owned by Elsevier.

Sclerotherapy 'provides more reproducible results withless discomfort and fewer complications.' DR. MANN

Pregnant women consumed just as much alcohol in 2005 as they did in 1991, with 12% drinking at least once during pregnancy and 2% reporting binge drinking.

The findings, published in the Morbidity and Mortality Weekly Report, illustrate the small effect of national educational programs aimed at decreasing the behavior, according to primary author Clark Denny, Ph.D.

In Healthy People 2010, the national health agenda published in 2000, Dr. David Satcher, the U.S. Surgeon General at that time, set abstinence targets of 95% for alcohol and 100% for binge drinking among pregnant women.

“The prevalence of both types of drinking behavior among pregnant women remains higher than the Healthy People 2010 targets and greater progress will be needed to reach them,” Dr. Denny wrote (MMWR 2009;58:529–32).

The 15-year study found that women aged 35–44 years had the highest incidence of drinking during pregnancy (18%), wrote Dr. Denny, an epidemiologist from the Centers for Disease Control and Prevention. Rates were also higher in college-educated women, employed women, and unmarried women.

The study was based on data collected from 1991 to 2005 through the Behavioral Risk Factor Surveillance System surveys. These annual surveys randomly poll community-dwelling U.S. adults about behavioral health issues. The CDC study included data collected from women aged 18–44 years, who were asked about alcohol use (at least one drink in the last 30 days) and binge drinking (at least five drinks on any one occasion in the last 30 days).

During the 15-year period, 533,500 women were surveyed; 22,000 (4%) reported being pregnant at the time of the survey. The average annual percentage of any alcohol use among the pregnant women was 12%, and did not change from 1991 to 2005. The average annual percentage of pregnant women who said they binged was 2%; again, that percentage was stable over the survey period.

From 2001 to 2005, the study also examined the relationship between drinking during pregnancy and demographic factors. Age was associated with both any drinking and binge drinking. The oldest women (35–44 years) had the highest drinking rate (18%), while the youngest women (18–24 years) had the lowest rate (9%). Age was not highly associated with binge drinking.

Any drinking was higher among employed women than unemployed (14% vs. 8%), and among unmarried women than married women (13% vs. 10%). Binge drinking was also more common among employed than unemployed women (2% vs. 1%), and unmarried women than married women (4% vs. 1%).

“Older women might be more likely to be alcohol dependent and have more difficult abstaining while pregnant; more educated and employed women might have more discretionary money for the purchase of alcohol; and unmarried women might attend more social occasions where alcohol is served.”

Rates of drinking and binge drinking were higher among nonpregnant women (54% and 12%, respectively). Prepregnancy alcohol use is a strong predictor of use during pregnancy, and many women who drink continue to do so before realizing that they are pregnant, Dr. Denny noted. “Approximately 40% of women realize they are pregnant at 4 weeks of gestation, a critical period for fetal organ development.”

“This study revealed that there is still a great need for health care professionals to routinely ask all women who are pregnant or at risk of being pregnant about their alcohol consumption,” he noted in a press statement.

Pregnant women consumed just as much alcohol in 2005 as they did in 1991, with 12% drinking at least once during pregnancy and 2% reporting binge drinking.

The findings, published in the Morbidity and Mortality Weekly Report, illustrate the small effect of national educational programs aimed at decreasing the behavior, according to primary author Clark Denny, Ph.D.

In Healthy People 2010, the national health agenda published in 2000, Dr. David Satcher, the U.S. Surgeon General at that time, set abstinence targets of 95% for alcohol and 100% for binge drinking among pregnant women.

“The prevalence of both types of drinking behavior among pregnant women remains higher than the Healthy People 2010 targets and greater progress will be needed to reach them,” Dr. Denny wrote (MMWR 2009;58:529–32).

The 15-year study found that women aged 35–44 years had the highest incidence of drinking during pregnancy (18%), wrote Dr. Denny, an epidemiologist from the Centers for Disease Control and Prevention. Rates were also higher in college-educated women, employed women, and unmarried women.

The study was based on data collected from 1991 to 2005 through the Behavioral Risk Factor Surveillance System surveys. These annual surveys randomly poll community-dwelling U.S. adults about behavioral health issues. The CDC study included data collected from women aged 18–44 years, who were asked about alcohol use (at least one drink in the last 30 days) and binge drinking (at least five drinks on any one occasion in the last 30 days).

During the 15-year period, 533,500 women were surveyed; 22,000 (4%) reported being pregnant at the time of the survey. The average annual percentage of any alcohol use among the pregnant women was 12%, and did not change from 1991 to 2005. The average annual percentage of pregnant women who said they binged was 2%; again, that percentage was stable over the survey period.

From 2001 to 2005, the study also examined the relationship between drinking during pregnancy and demographic factors. Age was associated with both any drinking and binge drinking. The oldest women (35–44 years) had the highest drinking rate (18%), while the youngest women (18–24 years) had the lowest rate (9%). Age was not highly associated with binge drinking.

Any drinking was higher among employed women than unemployed (14% vs. 8%), and among unmarried women than married women (13% vs. 10%). Binge drinking was also more common among employed than unemployed women (2% vs. 1%), and unmarried women than married women (4% vs. 1%).

“Older women might be more likely to be alcohol dependent and have more difficult abstaining while pregnant; more educated and employed women might have more discretionary money for the purchase of alcohol; and unmarried women might attend more social occasions where alcohol is served.”

Rates of drinking and binge drinking were higher among nonpregnant women (54% and 12%, respectively). Prepregnancy alcohol use is a strong predictor of use during pregnancy, and many women who drink continue to do so before realizing that they are pregnant, Dr. Denny noted. “Approximately 40% of women realize they are pregnant at 4 weeks of gestation, a critical period for fetal organ development.”

“This study revealed that there is still a great need for health care professionals to routinely ask all women who are pregnant or at risk of being pregnant about their alcohol consumption,” he noted in a press statement.

Pregnant women consumed just as much alcohol in 2005 as they did in 1991, with 12% drinking at least once during pregnancy and 2% reporting binge drinking.

The findings, published in the Morbidity and Mortality Weekly Report, illustrate the small effect of national educational programs aimed at decreasing the behavior, according to primary author Clark Denny, Ph.D.

In Healthy People 2010, the national health agenda published in 2000, Dr. David Satcher, the U.S. Surgeon General at that time, set abstinence targets of 95% for alcohol and 100% for binge drinking among pregnant women.

“The prevalence of both types of drinking behavior among pregnant women remains higher than the Healthy People 2010 targets and greater progress will be needed to reach them,” Dr. Denny wrote (MMWR 2009;58:529–32).

The 15-year study found that women aged 35–44 years had the highest incidence of drinking during pregnancy (18%), wrote Dr. Denny, an epidemiologist from the Centers for Disease Control and Prevention. Rates were also higher in college-educated women, employed women, and unmarried women.

The study was based on data collected from 1991 to 2005 through the Behavioral Risk Factor Surveillance System surveys. These annual surveys randomly poll community-dwelling U.S. adults about behavioral health issues. The CDC study included data collected from women aged 18–44 years, who were asked about alcohol use (at least one drink in the last 30 days) and binge drinking (at least five drinks on any one occasion in the last 30 days).

During the 15-year period, 533,500 women were surveyed; 22,000 (4%) reported being pregnant at the time of the survey. The average annual percentage of any alcohol use among the pregnant women was 12%, and did not change from 1991 to 2005. The average annual percentage of pregnant women who said they binged was 2%; again, that percentage was stable over the survey period.

From 2001 to 2005, the study also examined the relationship between drinking during pregnancy and demographic factors. Age was associated with both any drinking and binge drinking. The oldest women (35–44 years) had the highest drinking rate (18%), while the youngest women (18–24 years) had the lowest rate (9%). Age was not highly associated with binge drinking.

Any drinking was higher among employed women than unemployed (14% vs. 8%), and among unmarried women than married women (13% vs. 10%). Binge drinking was also more common among employed than unemployed women (2% vs. 1%), and unmarried women than married women (4% vs. 1%).

“Older women might be more likely to be alcohol dependent and have more difficult abstaining while pregnant; more educated and employed women might have more discretionary money for the purchase of alcohol; and unmarried women might attend more social occasions where alcohol is served.”

Rates of drinking and binge drinking were higher among nonpregnant women (54% and 12%, respectively). Prepregnancy alcohol use is a strong predictor of use during pregnancy, and many women who drink continue to do so before realizing that they are pregnant, Dr. Denny noted. “Approximately 40% of women realize they are pregnant at 4 weeks of gestation, a critical period for fetal organ development.”

“This study revealed that there is still a great need for health care professionals to routinely ask all women who are pregnant or at risk of being pregnant about their alcohol consumption,” he noted in a press statement.

CHICAGO — Drinking even two or fewer alcoholic drinks per day nearly quadruples the risk of hepatocellular carcinoma in patients with cirrhosis due to both nonalcoholic steatohepatitis and hepatitis C infection, a prospective study has concluded.

The study is the first to confirm such a link in patients with nonalcoholic steatohepatitis (NASH), and emphasizes the need for proactive counseling among these patients, Dr. Nizar Zein said at the annual Digestive Disease Week.

“Physicians following these patients should counsel complete abstention of alcohol,” Dr. Zein said in an interview. “If we can get them to do that, we may in the future be able to lower the burden of cancer associated with this disease.”

About 20% of patients with NASH will develop cirrhosis, a proven risk factor for hepatocellular carcinoma (HCC), said Dr. Zein, chief of hepatology and medical director of liver transplants at the Cleveland Clinic. “Despite this link, there is a lack of large population studies regarding the risk of HCC in patients with cirrhosis due to NASH.”

To study this question, Dr. Zein and his colleagues performed a retrospective analysis of 510 patients with cirrhosis not related to alcohol intake, who were treated at the clinic from 2003 to 2007. Cirrhosis was due to NASH in 195 patients, and to hepatitis C viral infection in 315. Patients with NASH were significantly older than those with hepatitis C (57 vs. 45 years). They also had a significantly higher body mass index (35 vs. 28 kg/m₂). The mean score on the Model for End-Stage Liver Disease (MELD) scale was 11 in the NASH group and 12 in the hepatitis group—not a significant difference.

Over the 3-year follow-up period, 18% of the entire study population developed HCC. The rate was significantly higher in the hepatitis group than in the NASH group (20% vs. 13%). The yearly HCC incidence was also significantly higher in the hepatitis C group than in the NASH group (4% per year vs. 3% per year).

A multivariate analysis examined risk factors associated with the development of HCC in those patients with NASH. Not surprisingly, older age at cirrhosis diagnosis was significantly associated with developing cancer, increasing the risk by 7%.

Even patients who drank only small amounts (fewer than two drinks per day) were almost four times more likely to develop HCC than were nondrinkers (hazard ratio 3.6). Heavy drinking (more than two drinks per day) increased HCC risk to the same extent as social drinking. Body mass index, smoking, diabetes, and MELD score were not significantly related to HCC in patients with NASH.

“This study shows for the first time that patients with NASH are at high risk for HCC, especially if they drink, and, as such, would probably benefit from a regular screening strategy,” Dr. Zein said.

No studies have addressed the optimum screening method. However, Dr. Zein said, a reasonable option might be ultrasound examination every 6 months.

CHICAGO — Drinking even two or fewer alcoholic drinks per day nearly quadruples the risk of hepatocellular carcinoma in patients with cirrhosis due to both nonalcoholic steatohepatitis and hepatitis C infection, a prospective study has concluded.

The study is the first to confirm such a link in patients with nonalcoholic steatohepatitis (NASH), and emphasizes the need for proactive counseling among these patients, Dr. Nizar Zein said at the annual Digestive Disease Week.

“Physicians following these patients should counsel complete abstention of alcohol,” Dr. Zein said in an interview. “If we can get them to do that, we may in the future be able to lower the burden of cancer associated with this disease.”

About 20% of patients with NASH will develop cirrhosis, a proven risk factor for hepatocellular carcinoma (HCC), said Dr. Zein, chief of hepatology and medical director of liver transplants at the Cleveland Clinic. “Despite this link, there is a lack of large population studies regarding the risk of HCC in patients with cirrhosis due to NASH.”

To study this question, Dr. Zein and his colleagues performed a retrospective analysis of 510 patients with cirrhosis not related to alcohol intake, who were treated at the clinic from 2003 to 2007. Cirrhosis was due to NASH in 195 patients, and to hepatitis C viral infection in 315. Patients with NASH were significantly older than those with hepatitis C (57 vs. 45 years). They also had a significantly higher body mass index (35 vs. 28 kg/m₂). The mean score on the Model for End-Stage Liver Disease (MELD) scale was 11 in the NASH group and 12 in the hepatitis group—not a significant difference.

Over the 3-year follow-up period, 18% of the entire study population developed HCC. The rate was significantly higher in the hepatitis group than in the NASH group (20% vs. 13%). The yearly HCC incidence was also significantly higher in the hepatitis C group than in the NASH group (4% per year vs. 3% per year).

A multivariate analysis examined risk factors associated with the development of HCC in those patients with NASH. Not surprisingly, older age at cirrhosis diagnosis was significantly associated with developing cancer, increasing the risk by 7%.

Even patients who drank only small amounts (fewer than two drinks per day) were almost four times more likely to develop HCC than were nondrinkers (hazard ratio 3.6). Heavy drinking (more than two drinks per day) increased HCC risk to the same extent as social drinking. Body mass index, smoking, diabetes, and MELD score were not significantly related to HCC in patients with NASH.

“This study shows for the first time that patients with NASH are at high risk for HCC, especially if they drink, and, as such, would probably benefit from a regular screening strategy,” Dr. Zein said.

No studies have addressed the optimum screening method. However, Dr. Zein said, a reasonable option might be ultrasound examination every 6 months.

CHICAGO — Drinking even two or fewer alcoholic drinks per day nearly quadruples the risk of hepatocellular carcinoma in patients with cirrhosis due to both nonalcoholic steatohepatitis and hepatitis C infection, a prospective study has concluded.

The study is the first to confirm such a link in patients with nonalcoholic steatohepatitis (NASH), and emphasizes the need for proactive counseling among these patients, Dr. Nizar Zein said at the annual Digestive Disease Week.

“Physicians following these patients should counsel complete abstention of alcohol,” Dr. Zein said in an interview. “If we can get them to do that, we may in the future be able to lower the burden of cancer associated with this disease.”

About 20% of patients with NASH will develop cirrhosis, a proven risk factor for hepatocellular carcinoma (HCC), said Dr. Zein, chief of hepatology and medical director of liver transplants at the Cleveland Clinic. “Despite this link, there is a lack of large population studies regarding the risk of HCC in patients with cirrhosis due to NASH.”

To study this question, Dr. Zein and his colleagues performed a retrospective analysis of 510 patients with cirrhosis not related to alcohol intake, who were treated at the clinic from 2003 to 2007. Cirrhosis was due to NASH in 195 patients, and to hepatitis C viral infection in 315. Patients with NASH were significantly older than those with hepatitis C (57 vs. 45 years). They also had a significantly higher body mass index (35 vs. 28 kg/m₂). The mean score on the Model for End-Stage Liver Disease (MELD) scale was 11 in the NASH group and 12 in the hepatitis group—not a significant difference.

Over the 3-year follow-up period, 18% of the entire study population developed HCC. The rate was significantly higher in the hepatitis group than in the NASH group (20% vs. 13%). The yearly HCC incidence was also significantly higher in the hepatitis C group than in the NASH group (4% per year vs. 3% per year).

A multivariate analysis examined risk factors associated with the development of HCC in those patients with NASH. Not surprisingly, older age at cirrhosis diagnosis was significantly associated with developing cancer, increasing the risk by 7%.

Even patients who drank only small amounts (fewer than two drinks per day) were almost four times more likely to develop HCC than were nondrinkers (hazard ratio 3.6). Heavy drinking (more than two drinks per day) increased HCC risk to the same extent as social drinking. Body mass index, smoking, diabetes, and MELD score were not significantly related to HCC in patients with NASH.

“This study shows for the first time that patients with NASH are at high risk for HCC, especially if they drink, and, as such, would probably benefit from a regular screening strategy,” Dr. Zein said.

No studies have addressed the optimum screening method. However, Dr. Zein said, a reasonable option might be ultrasound examination every 6 months.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.