Kerri Wachter

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will be presenting the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA. The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S.-licensed vaccines.

Dr. Souayah searched the database using several key words: “numbness,” “tingling,” “Guillain,” “Barré,” and “Guillain-Barré syndrome.” He identified roughly 350 patients. He then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine in 2006–2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the Guillain-Barré syndrome cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternately, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will be presenting the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA. The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S.-licensed vaccines.

Dr. Souayah searched the database using several key words: “numbness,” “tingling,” “Guillain,” “Barré,” and “Guillain-Barré syndrome.” He identified roughly 350 patients. He then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine in 2006–2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the Guillain-Barré syndrome cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternately, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will be presenting the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA. The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S.-licensed vaccines.

Dr. Souayah searched the database using several key words: “numbness,” “tingling,” “Guillain,” “Barré,” and “Guillain-Barré syndrome.” He identified roughly 350 patients. He then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine in 2006–2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the Guillain-Barré syndrome cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternately, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

FORT MYERS, FLA. — Severely obese patients are more likely other patients to develop common complications and to die following trauma, according to a retrospective study of more than 1.3 million patients.

An analysis of National Trauma Data Bank records for more than 1,373,777 trauma patients from 2002 to 2006 found that severely obese patients were 19% more likely to die, compared with other patients, based on crude mortality (odds ratio 1.19). After adjustment, severely obese patients had an even greater risk of death following trauma (OR 1.30), Dr. Neema Kaseje reported at the annual Academic Surgical Congress.

A total of 7,962 trauma patients with a body mass index of more than 40 kg/m

Dr. Kaseje and her colleagues at the Center for Surgery and Public Health at Harvard University in Boston conducted their study to determine if mortality and morbidity following trauma differed between patients who are severely obese and those who are not. The primary outcome was in-hospital mortality. Secondary outcomes included rates of pneumonia, urinary tract infection, wound infection, bacteremia, disseminated fungal infection, and empyema. The researchers adjusted for age, gender, Injury Severity Score (ISS), and insurance status.

Compared with the other patients in the database, severely obese patients were more likely to be older than 49 years (50% vs. 28%, respectively), to be female (53% vs. 34%), to have an ISS greater than 25, and to have health insurance (85% vs. 78%). Severely obese patients also had significantly greater rates of pneumonia (OR 1.73), urinary tract infection (OR 3.25), wound infection (OR 2.16), bacteremia (OR 3.46), and disseminated fungal infection (OR 4.87).

A major limitation of the study is that the data did not include actual BMIs. In the database, patients were classified either as obese (BMI greater than 40 kg/m

FORT MYERS, FLA. — Severely obese patients are more likely other patients to develop common complications and to die following trauma, according to a retrospective study of more than 1.3 million patients.

An analysis of National Trauma Data Bank records for more than 1,373,777 trauma patients from 2002 to 2006 found that severely obese patients were 19% more likely to die, compared with other patients, based on crude mortality (odds ratio 1.19). After adjustment, severely obese patients had an even greater risk of death following trauma (OR 1.30), Dr. Neema Kaseje reported at the annual Academic Surgical Congress.

A total of 7,962 trauma patients with a body mass index of more than 40 kg/m

Dr. Kaseje and her colleagues at the Center for Surgery and Public Health at Harvard University in Boston conducted their study to determine if mortality and morbidity following trauma differed between patients who are severely obese and those who are not. The primary outcome was in-hospital mortality. Secondary outcomes included rates of pneumonia, urinary tract infection, wound infection, bacteremia, disseminated fungal infection, and empyema. The researchers adjusted for age, gender, Injury Severity Score (ISS), and insurance status.

Compared with the other patients in the database, severely obese patients were more likely to be older than 49 years (50% vs. 28%, respectively), to be female (53% vs. 34%), to have an ISS greater than 25, and to have health insurance (85% vs. 78%). Severely obese patients also had significantly greater rates of pneumonia (OR 1.73), urinary tract infection (OR 3.25), wound infection (OR 2.16), bacteremia (OR 3.46), and disseminated fungal infection (OR 4.87).

A major limitation of the study is that the data did not include actual BMIs. In the database, patients were classified either as obese (BMI greater than 40 kg/m

FORT MYERS, FLA. — Severely obese patients are more likely other patients to develop common complications and to die following trauma, according to a retrospective study of more than 1.3 million patients.

An analysis of National Trauma Data Bank records for more than 1,373,777 trauma patients from 2002 to 2006 found that severely obese patients were 19% more likely to die, compared with other patients, based on crude mortality (odds ratio 1.19). After adjustment, severely obese patients had an even greater risk of death following trauma (OR 1.30), Dr. Neema Kaseje reported at the annual Academic Surgical Congress.

A total of 7,962 trauma patients with a body mass index of more than 40 kg/m

Dr. Kaseje and her colleagues at the Center for Surgery and Public Health at Harvard University in Boston conducted their study to determine if mortality and morbidity following trauma differed between patients who are severely obese and those who are not. The primary outcome was in-hospital mortality. Secondary outcomes included rates of pneumonia, urinary tract infection, wound infection, bacteremia, disseminated fungal infection, and empyema. The researchers adjusted for age, gender, Injury Severity Score (ISS), and insurance status.

Compared with the other patients in the database, severely obese patients were more likely to be older than 49 years (50% vs. 28%, respectively), to be female (53% vs. 34%), to have an ISS greater than 25, and to have health insurance (85% vs. 78%). Severely obese patients also had significantly greater rates of pneumonia (OR 1.73), urinary tract infection (OR 3.25), wound infection (OR 2.16), bacteremia (OR 3.46), and disseminated fungal infection (OR 4.87).

A major limitation of the study is that the data did not include actual BMIs. In the database, patients were classified either as obese (BMI greater than 40 kg/m

SAN ANTONIO — The addition of the bisphosphonate zoledronic acid to standard neoadjuvant chemotherapy reduces tumor size and results in more patients with a pathologic complete response than does chemotherapy alone, which suggests that the drug has direct antitumor activity, study results showed.

In a retrospective exploratory analysis involving more than 200 women, the adjusted mean residual invasive tumor sizes (RITS) in chemotherapy-alone and chemotherapy plus zoledronic acid groups were 42.4 mm and 28.2 mm, respectively—a significant difference (P = .002), Dr. Robert Coleman reported at the annual San Antonio Breast Cancer Symposium.

The pathologic complete response (pCR) rate (both breast and axilla) was 5.8% in the chemotherapy-alone arm and 10.9% in the combination arm (P = .033). In a multivariate analysis, the difference in pCR significantly favored the combination arm with an odds ratio of 3.7 (P = .03).

“It is the first patient-related evidence that this class of drugs may have direct antitumor activity,” he said at a press conference during the meeting. “What these data suggest is that perhaps zoledronic acid is doing something more than just affecting bone.” Dr. Coleman, an oncologist at the cancer research centre at Weston Park Hospital in Sheffield, England, presented the findings in a poster at the meeting.

“This is not a practice-changing study,” he cautioned. “It's a hypothesis-generating study, which will lead to the design of specific neoadjuvant trials to look at this in more detail.”

In the Neo-Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, 3,360 women with stage II/III breast cancer were recruited to determine whether treatment with zoledronic acid in addition to neoadjuvant therapy improves disease-related outcomes. Women had to have a tumor size greater than 5 cm (T3) or features of locally advanced disease (T4) or biopsy-proven lymph node involvement (N1).

They also had to be scheduled for definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy. In addition, the time between the start of neoadjuvant treatment and the start of zoledronic acid had to be no greater than 30 days.

In AZURE, eligible patients received neoadjuvant chemotherapy according to local practice and were randomized to also receive 4 mg IV zoledronic acid (every 3–4 weeks for 6 months in the neoadjuvant period) or no additional treatment.

The primary surrogate end point for response was RITS at surgery. Secondary end points included pCR, number of positive axillary nodes, and percentage of patients requiring mastectomy. In a multivariate analysis, the researchers adjusted for T stage, estrogen-receptor and progesterone-receptor status, chemotherapy type (anthracycline/taxane), treatment duration, and menopausal status, Dr. Coleman said.

A total of 205 patients received neoadjuvant chemotherapy—104 in the chemotherapy-alone group and 101 in the chemotherapy plus zoledronic acid group. The baseline characteristics and treatments were similar, and the median number of chemotherapy cycles and treatment duration were the same in both groups.

Most women in both arms were estrogen-receptor positive—64% in the chemotherapy-alone arm and 68% in the combination arm.

In terms of progesterone-receptor status, 46% of the women in the chemotherapy-alone arm were negative, 25% were positive, and 29% were of unknown status; in the zoledronic acid arm, 34% were negative, about a third were positive, and a third were of unknown status.

Almost half of the women in both arms were HER2 positive—47% in the chemotherapy-alone arm and 48% in the combination arm.

The unadjusted median RITS was 30 mm in the chemotherapy-alone group, compared with only 20.5 mm in the combination group. In a multivariate analysis (171 patients with complete data), zoledronic acid, estrogen-receptor status (P = .034), and treatment duration (P = .002) were independent significant predictors of smaller RITS with negative estrogen-receptor status and increasing treatment duration.

There was no significant difference in the median number of positive lymph nodes at surgery. The proportion of patients requiring mastectomy in the chemotherapy-alone and combination arms was 77.9% and 65.3%.

Dr. Coleman reported that he has received grant support from Novartis and he is on the speakers bureau with Novartis and Amgen Inc. Novartis makes Zometa. The study was sponsored in part by Novartis.

'It is the first patient-related evidence that this class of drugs may have direct antitumor activity.' DR. COLEMAN

SAN ANTONIO — The addition of the bisphosphonate zoledronic acid to standard neoadjuvant chemotherapy reduces tumor size and results in more patients with a pathologic complete response than does chemotherapy alone, which suggests that the drug has direct antitumor activity, study results showed.

In a retrospective exploratory analysis involving more than 200 women, the adjusted mean residual invasive tumor sizes (RITS) in chemotherapy-alone and chemotherapy plus zoledronic acid groups were 42.4 mm and 28.2 mm, respectively—a significant difference (P = .002), Dr. Robert Coleman reported at the annual San Antonio Breast Cancer Symposium.

The pathologic complete response (pCR) rate (both breast and axilla) was 5.8% in the chemotherapy-alone arm and 10.9% in the combination arm (P = .033). In a multivariate analysis, the difference in pCR significantly favored the combination arm with an odds ratio of 3.7 (P = .03).

“It is the first patient-related evidence that this class of drugs may have direct antitumor activity,” he said at a press conference during the meeting. “What these data suggest is that perhaps zoledronic acid is doing something more than just affecting bone.” Dr. Coleman, an oncologist at the cancer research centre at Weston Park Hospital in Sheffield, England, presented the findings in a poster at the meeting.

“This is not a practice-changing study,” he cautioned. “It's a hypothesis-generating study, which will lead to the design of specific neoadjuvant trials to look at this in more detail.”

In the Neo-Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, 3,360 women with stage II/III breast cancer were recruited to determine whether treatment with zoledronic acid in addition to neoadjuvant therapy improves disease-related outcomes. Women had to have a tumor size greater than 5 cm (T3) or features of locally advanced disease (T4) or biopsy-proven lymph node involvement (N1).

They also had to be scheduled for definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy. In addition, the time between the start of neoadjuvant treatment and the start of zoledronic acid had to be no greater than 30 days.

In AZURE, eligible patients received neoadjuvant chemotherapy according to local practice and were randomized to also receive 4 mg IV zoledronic acid (every 3–4 weeks for 6 months in the neoadjuvant period) or no additional treatment.

The primary surrogate end point for response was RITS at surgery. Secondary end points included pCR, number of positive axillary nodes, and percentage of patients requiring mastectomy. In a multivariate analysis, the researchers adjusted for T stage, estrogen-receptor and progesterone-receptor status, chemotherapy type (anthracycline/taxane), treatment duration, and menopausal status, Dr. Coleman said.

A total of 205 patients received neoadjuvant chemotherapy—104 in the chemotherapy-alone group and 101 in the chemotherapy plus zoledronic acid group. The baseline characteristics and treatments were similar, and the median number of chemotherapy cycles and treatment duration were the same in both groups.

Most women in both arms were estrogen-receptor positive—64% in the chemotherapy-alone arm and 68% in the combination arm.

In terms of progesterone-receptor status, 46% of the women in the chemotherapy-alone arm were negative, 25% were positive, and 29% were of unknown status; in the zoledronic acid arm, 34% were negative, about a third were positive, and a third were of unknown status.

Almost half of the women in both arms were HER2 positive—47% in the chemotherapy-alone arm and 48% in the combination arm.

The unadjusted median RITS was 30 mm in the chemotherapy-alone group, compared with only 20.5 mm in the combination group. In a multivariate analysis (171 patients with complete data), zoledronic acid, estrogen-receptor status (P = .034), and treatment duration (P = .002) were independent significant predictors of smaller RITS with negative estrogen-receptor status and increasing treatment duration.

There was no significant difference in the median number of positive lymph nodes at surgery. The proportion of patients requiring mastectomy in the chemotherapy-alone and combination arms was 77.9% and 65.3%.

Dr. Coleman reported that he has received grant support from Novartis and he is on the speakers bureau with Novartis and Amgen Inc. Novartis makes Zometa. The study was sponsored in part by Novartis.

'It is the first patient-related evidence that this class of drugs may have direct antitumor activity.' DR. COLEMAN

SAN ANTONIO — The addition of the bisphosphonate zoledronic acid to standard neoadjuvant chemotherapy reduces tumor size and results in more patients with a pathologic complete response than does chemotherapy alone, which suggests that the drug has direct antitumor activity, study results showed.

In a retrospective exploratory analysis involving more than 200 women, the adjusted mean residual invasive tumor sizes (RITS) in chemotherapy-alone and chemotherapy plus zoledronic acid groups were 42.4 mm and 28.2 mm, respectively—a significant difference (P = .002), Dr. Robert Coleman reported at the annual San Antonio Breast Cancer Symposium.

The pathologic complete response (pCR) rate (both breast and axilla) was 5.8% in the chemotherapy-alone arm and 10.9% in the combination arm (P = .033). In a multivariate analysis, the difference in pCR significantly favored the combination arm with an odds ratio of 3.7 (P = .03).

“It is the first patient-related evidence that this class of drugs may have direct antitumor activity,” he said at a press conference during the meeting. “What these data suggest is that perhaps zoledronic acid is doing something more than just affecting bone.” Dr. Coleman, an oncologist at the cancer research centre at Weston Park Hospital in Sheffield, England, presented the findings in a poster at the meeting.

“This is not a practice-changing study,” he cautioned. “It's a hypothesis-generating study, which will lead to the design of specific neoadjuvant trials to look at this in more detail.”

In the Neo-Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, 3,360 women with stage II/III breast cancer were recruited to determine whether treatment with zoledronic acid in addition to neoadjuvant therapy improves disease-related outcomes. Women had to have a tumor size greater than 5 cm (T3) or features of locally advanced disease (T4) or biopsy-proven lymph node involvement (N1).

They also had to be scheduled for definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy. In addition, the time between the start of neoadjuvant treatment and the start of zoledronic acid had to be no greater than 30 days.

In AZURE, eligible patients received neoadjuvant chemotherapy according to local practice and were randomized to also receive 4 mg IV zoledronic acid (every 3–4 weeks for 6 months in the neoadjuvant period) or no additional treatment.

The primary surrogate end point for response was RITS at surgery. Secondary end points included pCR, number of positive axillary nodes, and percentage of patients requiring mastectomy. In a multivariate analysis, the researchers adjusted for T stage, estrogen-receptor and progesterone-receptor status, chemotherapy type (anthracycline/taxane), treatment duration, and menopausal status, Dr. Coleman said.

A total of 205 patients received neoadjuvant chemotherapy—104 in the chemotherapy-alone group and 101 in the chemotherapy plus zoledronic acid group. The baseline characteristics and treatments were similar, and the median number of chemotherapy cycles and treatment duration were the same in both groups.

Most women in both arms were estrogen-receptor positive—64% in the chemotherapy-alone arm and 68% in the combination arm.

In terms of progesterone-receptor status, 46% of the women in the chemotherapy-alone arm were negative, 25% were positive, and 29% were of unknown status; in the zoledronic acid arm, 34% were negative, about a third were positive, and a third were of unknown status.

Almost half of the women in both arms were HER2 positive—47% in the chemotherapy-alone arm and 48% in the combination arm.

The unadjusted median RITS was 30 mm in the chemotherapy-alone group, compared with only 20.5 mm in the combination group. In a multivariate analysis (171 patients with complete data), zoledronic acid, estrogen-receptor status (P = .034), and treatment duration (P = .002) were independent significant predictors of smaller RITS with negative estrogen-receptor status and increasing treatment duration.

There was no significant difference in the median number of positive lymph nodes at surgery. The proportion of patients requiring mastectomy in the chemotherapy-alone and combination arms was 77.9% and 65.3%.

Dr. Coleman reported that he has received grant support from Novartis and he is on the speakers bureau with Novartis and Amgen Inc. Novartis makes Zometa. The study was sponsored in part by Novartis.

'It is the first patient-related evidence that this class of drugs may have direct antitumor activity.' DR. COLEMAN

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will present the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA.

The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S. licensed vaccines.

Dr. Souayah searched the database using the key words: “Guillain,” “Barré,” “Guillain-Barré syndrome,” “numbness,” and “tingling.” He identified roughly 350 patients, then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine between 2006 and 2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the [GBS] cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternatively, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will present the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA.

The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S. licensed vaccines.

Dr. Souayah searched the database using the key words: “Guillain,” “Barré,” “Guillain-Barré syndrome,” “numbness,” and “tingling.” He identified roughly 350 patients, then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine between 2006 and 2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the [GBS] cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternatively, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

The human papillomavirus vaccine does not appear to increase the risk of developing Guillain-Barré syndrome, despite isolated reports of the condition following vaccination, a study shows.

“I found that there's some overlap between the incidence of Guillain-Barré in the general population and Guillain-Barré after vaccination with Gardasil,” Dr. Nizar Souayah said in an interview. However, he and his colleagues have not found Guillain-Barré to occur more often among those who have received the HPV vaccine than among people in the general population.

Dr. Souayah will present the study at the American Academy of Neurology annual meeting in Seattle, April 25-May 2. The data were released early.

The Food and Drug Administration approved the vaccine in 2006 for use in girls and women aged 9–26 years to prevent infection against HPV strains 16 and 18, which cause most cervical cancers, and strains 6 and 11, which are responsible for most genital warts in the United States. Since the approval of Gardasil, more than 16 million doses have been given. There have been isolated reports of Guillain-Barré syndrome (GBS) after receiving the vaccine.

Dr. Souayah and his colleagues used data from the Vaccine Adverse Event Reporting System, which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention and the FDA.

The system is a postmarketing safety surveillance program that collects information about adverse events that occur after the administration of U.S. licensed vaccines.

Dr. Souayah searched the database using the key words: “Guillain,” “Barré,” “Guillain-Barré syndrome,” “numbness,” and “tingling.” He identified roughly 350 patients, then reviewed the data for each of these patients and characterized them as highly likely to have GBS, highly unlikely to have GBS, and unclear. He and his colleagues included in this analysis only those patients considered to be highly likely to have GBS.

They found 36 reported cases of GBS after vaccination with the HPV vaccine between 2006 and 2008. The mean age was 17 years. The estimated incidence of GBS after vaccination is 7 cases per million vaccinations. In comparison, the estimated incidence for the general population is 4–10 cases per million individuals.

“The most striking data [are] that most of the [GBS] cases occurred within 6 weeks of vaccination,” said Dr. Souayah, of the departments of neurology and neurosciences at the University of Medicine and Dentistry of New Jersey, Newark. The onset of GBS occurred within 6 weeks of vaccination in 75% of the individuals for whom the vaccination date was known.

“Our results show that Guillain-Barré is not occurring more often after HPV vaccination than it does in the general population. However, the fact that most of these cases occurred within 6 weeks of vaccination does warrant careful monitoring for any additional cases and continued analysis,” he said in a statement.

He urged caution in interpreting the results. The database may not contain all cases of GBS after administration of the HPV vaccine; alternatively, the database might contain cases that were not confirmed. “I would like to emphasize that we need more research,” he said.

Mortality and length of stay following colon resection are significantly reduced at nonteaching hospitals compared with teaching hospitals, according to a retrospective analysis of 6 years' worth of data in the National Inpatient Sample.

Following risk and volume adjustment, teaching hospitals were associated with a 14% increased risk of operative mortality, Dr. Awori J. Hayanga reported at the annual Academic Surgical Congress in Fort Myers, Fla. In addition, there was a significant increase in length of stay—10.4 days at teaching hospitals vs. 8.5 days at nonteaching hospitals—and a trend toward an increase in total charges from about $6,000 to more than $8,000.

“The assumption is that teaching hospitals have higher volumes for all procedures, and that's not the case. … Most colon resections in the United States are not performed in teaching hospitals,” Dr. Hayanga said in an interview. “Cancer makes up the minority of resections that are performed on the colon. More resections are performed for benign disease.” The bulk of resections for benign colon disease are performed at nonteaching hospitals.

“We are postulating that there might be a tipping point in the volume-outcome ratio that shifts in favor of nonteaching hospitals—once you hit the critical volume of procedures,” said Dr. Hayanga, a surgical resident at the University of Michigan in Ann Arbor.

The analysis conducted by Dr. Hayanga and his colleagues was supplemented with data from the Area Resource File and the National Inpatient Sample. Logistic regression analysis was used to estimate 30-day mortality while linear regression analysis was used to estimate both length of stay and total charges. A teaching hospital met the definition by the American Hospital Association and was affiliated with either an Accreditation Council for Graduate Medical Education-accredited general surgery residency and/or colon fellowship at the institution.

The analysis included patients over the age of 18 who had undergone a colon resection as classified by ICD-9 codes.

Covariates included age, sex, race, insurance status, geographic region, institutional volume and urban/suburban/rural status, median county income, and percentage of county residents living below the federal poverty level.

“Teaching hospitals—with their propensity for performing rare and specialized surgery—tend to see sicker patients, who require the resources that are available only at these tertiary centers to get these patients better,” Dr. Hayanga said. “There is a feeling that there is a qualitatively different patient who comes to teaching hospitals.”

To attempt to control for possible differences in the types of patients seen at teaching vs. nonteaching hospitals, the investigators included the Charlson comorbidity index as a covariate.

In all, 115,250 patients underwent colon resection during the time period at more than 2,000 hospitals. Most patients (60%) received care at nonteaching hospitals. Overall, the mortality rate was 3.8%.

The researchers concluded that teaching hospitals may offer improved outcomes for complex oncologic surgical resections but may have worse outcomes for less complex surgery. Most of the less complex procedures are performed at nonteaching hospitals.

The databases have some limitations, and the study raises more questions than it answers, Dr. Hayanga acknowledged, adding that to accurately determine this relationship, a randomized prospective study would be needed for further clarification.

Mortality and length of stay following colon resection are significantly reduced at nonteaching hospitals compared with teaching hospitals, according to a retrospective analysis of 6 years' worth of data in the National Inpatient Sample.

Following risk and volume adjustment, teaching hospitals were associated with a 14% increased risk of operative mortality, Dr. Awori J. Hayanga reported at the annual Academic Surgical Congress in Fort Myers, Fla. In addition, there was a significant increase in length of stay—10.4 days at teaching hospitals vs. 8.5 days at nonteaching hospitals—and a trend toward an increase in total charges from about $6,000 to more than $8,000.

“The assumption is that teaching hospitals have higher volumes for all procedures, and that's not the case. … Most colon resections in the United States are not performed in teaching hospitals,” Dr. Hayanga said in an interview. “Cancer makes up the minority of resections that are performed on the colon. More resections are performed for benign disease.” The bulk of resections for benign colon disease are performed at nonteaching hospitals.

“We are postulating that there might be a tipping point in the volume-outcome ratio that shifts in favor of nonteaching hospitals—once you hit the critical volume of procedures,” said Dr. Hayanga, a surgical resident at the University of Michigan in Ann Arbor.

The analysis conducted by Dr. Hayanga and his colleagues was supplemented with data from the Area Resource File and the National Inpatient Sample. Logistic regression analysis was used to estimate 30-day mortality while linear regression analysis was used to estimate both length of stay and total charges. A teaching hospital met the definition by the American Hospital Association and was affiliated with either an Accreditation Council for Graduate Medical Education-accredited general surgery residency and/or colon fellowship at the institution.

The analysis included patients over the age of 18 who had undergone a colon resection as classified by ICD-9 codes.

Covariates included age, sex, race, insurance status, geographic region, institutional volume and urban/suburban/rural status, median county income, and percentage of county residents living below the federal poverty level.

“Teaching hospitals—with their propensity for performing rare and specialized surgery—tend to see sicker patients, who require the resources that are available only at these tertiary centers to get these patients better,” Dr. Hayanga said. “There is a feeling that there is a qualitatively different patient who comes to teaching hospitals.”

To attempt to control for possible differences in the types of patients seen at teaching vs. nonteaching hospitals, the investigators included the Charlson comorbidity index as a covariate.

In all, 115,250 patients underwent colon resection during the time period at more than 2,000 hospitals. Most patients (60%) received care at nonteaching hospitals. Overall, the mortality rate was 3.8%.

The researchers concluded that teaching hospitals may offer improved outcomes for complex oncologic surgical resections but may have worse outcomes for less complex surgery. Most of the less complex procedures are performed at nonteaching hospitals.

The databases have some limitations, and the study raises more questions than it answers, Dr. Hayanga acknowledged, adding that to accurately determine this relationship, a randomized prospective study would be needed for further clarification.

Mortality and length of stay following colon resection are significantly reduced at nonteaching hospitals compared with teaching hospitals, according to a retrospective analysis of 6 years' worth of data in the National Inpatient Sample.

Following risk and volume adjustment, teaching hospitals were associated with a 14% increased risk of operative mortality, Dr. Awori J. Hayanga reported at the annual Academic Surgical Congress in Fort Myers, Fla. In addition, there was a significant increase in length of stay—10.4 days at teaching hospitals vs. 8.5 days at nonteaching hospitals—and a trend toward an increase in total charges from about $6,000 to more than $8,000.

“The assumption is that teaching hospitals have higher volumes for all procedures, and that's not the case. … Most colon resections in the United States are not performed in teaching hospitals,” Dr. Hayanga said in an interview. “Cancer makes up the minority of resections that are performed on the colon. More resections are performed for benign disease.” The bulk of resections for benign colon disease are performed at nonteaching hospitals.

“We are postulating that there might be a tipping point in the volume-outcome ratio that shifts in favor of nonteaching hospitals—once you hit the critical volume of procedures,” said Dr. Hayanga, a surgical resident at the University of Michigan in Ann Arbor.

The analysis conducted by Dr. Hayanga and his colleagues was supplemented with data from the Area Resource File and the National Inpatient Sample. Logistic regression analysis was used to estimate 30-day mortality while linear regression analysis was used to estimate both length of stay and total charges. A teaching hospital met the definition by the American Hospital Association and was affiliated with either an Accreditation Council for Graduate Medical Education-accredited general surgery residency and/or colon fellowship at the institution.

The analysis included patients over the age of 18 who had undergone a colon resection as classified by ICD-9 codes.

Covariates included age, sex, race, insurance status, geographic region, institutional volume and urban/suburban/rural status, median county income, and percentage of county residents living below the federal poverty level.

“Teaching hospitals—with their propensity for performing rare and specialized surgery—tend to see sicker patients, who require the resources that are available only at these tertiary centers to get these patients better,” Dr. Hayanga said. “There is a feeling that there is a qualitatively different patient who comes to teaching hospitals.”

To attempt to control for possible differences in the types of patients seen at teaching vs. nonteaching hospitals, the investigators included the Charlson comorbidity index as a covariate.

In all, 115,250 patients underwent colon resection during the time period at more than 2,000 hospitals. Most patients (60%) received care at nonteaching hospitals. Overall, the mortality rate was 3.8%.

The researchers concluded that teaching hospitals may offer improved outcomes for complex oncologic surgical resections but may have worse outcomes for less complex surgery. Most of the less complex procedures are performed at nonteaching hospitals.

The databases have some limitations, and the study raises more questions than it answers, Dr. Hayanga acknowledged, adding that to accurately determine this relationship, a randomized prospective study would be needed for further clarification.

FORT MYERS, FLA. — The difference between successful and unsuccessful treatment of patients for postsurgical complications may help account for the wide variability in mortality rates following major surgery at hospitals nationwide, according to a retrospective study of data for more than 12,000 patients.

“High-mortality hospitals have mortality rates similar to those of low-mortality hospitals but markedly higher failure-to-rescue rates,” Dr. Amir A. Ghaferi said at the annual Academic Surgical Congress.

The failure-to-rescue rate (i.e., mortality following the development of a postsurgical complication) for high-mortality hospitals was more than twice that for low-mortality hospitals—26% versus 11%, respectively. “When we evaluated individual complications, this trend persisted,” said Dr. Ghaferi, a surgical resident at the University of Michigan, Ann Arbor.

Wide variability in mortality rates following major surgery has been noted previously. Dr. Ghaferi and his coinvestigators hypothesized that hospitals with higher mortality rates are less effective than low-mortality hospitals in rescuing patients, once they develop complications, and that this could account for some of the variability.

To test their hypothesis, they analyzed data from the American College of Surgeons' National Surgical Quality Improvement Program for all patients undergoing colectomy in 2005-2006. Data were available for 12,688 patients. Primary outcomes included 30-day mortality, the development of one of nine major postoperative complications (pneumonia, unplanned intubation, pulmonary embolism, myocardial infarction, acute renal failure, postoperative bleeding, deep wound infection, organ-space infection, and fascial dehiscence), and the mortality rates following each of these complications.

In all, 123 hospitals were grouped into quintiles by their risk-adjusted mortality rates. The investigators controlled 27 variables in the risk-adjustment model, including age, sex, race, and American Society of Anesthesiologists physical status classification. Risk-adjusted mortality rates ranged from 1.5% to 7.4% across the groups. Next, they compared complication rates for the nine common postoperative complications across the groups, as well as failure-to-rescue rates (i.e., rates of death caused by any of the nine postoperative complications).

A total of 51% of patients were female, and most (81%) were white, with a mean body mass index of 27 kg/m

High-mortality hospitals had a 1.5-fold greater risk of postsurgical complications: 16.2% in the high-mortality group, compared with 12.7% in the low-mortality group. “This cannot explain the nearly threefold mortality rate difference across our hospitals. However, when we looked at the failure-to-rescue rate, there's an astonishing difference,” he said.

“Many existing policies, which are aimed at reducing the incidence of complications, may not be able to reduce this observed variation in mortality. Rather, we may need to focus on the timely recognition and management of complications once they occur. The next step will be to develop a better understanding of the hospital resources and processes of care that lead to rescue from postsurgical complications.”

Dr. Ghaferi reported that he has no relevant financial relationships.

FORT MYERS, FLA. — The difference between successful and unsuccessful treatment of patients for postsurgical complications may help account for the wide variability in mortality rates following major surgery at hospitals nationwide, according to a retrospective study of data for more than 12,000 patients.

“High-mortality hospitals have mortality rates similar to those of low-mortality hospitals but markedly higher failure-to-rescue rates,” Dr. Amir A. Ghaferi said at the annual Academic Surgical Congress.

The failure-to-rescue rate (i.e., mortality following the development of a postsurgical complication) for high-mortality hospitals was more than twice that for low-mortality hospitals—26% versus 11%, respectively. “When we evaluated individual complications, this trend persisted,” said Dr. Ghaferi, a surgical resident at the University of Michigan, Ann Arbor.

Wide variability in mortality rates following major surgery has been noted previously. Dr. Ghaferi and his coinvestigators hypothesized that hospitals with higher mortality rates are less effective than low-mortality hospitals in rescuing patients, once they develop complications, and that this could account for some of the variability.

To test their hypothesis, they analyzed data from the American College of Surgeons' National Surgical Quality Improvement Program for all patients undergoing colectomy in 2005-2006. Data were available for 12,688 patients. Primary outcomes included 30-day mortality, the development of one of nine major postoperative complications (pneumonia, unplanned intubation, pulmonary embolism, myocardial infarction, acute renal failure, postoperative bleeding, deep wound infection, organ-space infection, and fascial dehiscence), and the mortality rates following each of these complications.

In all, 123 hospitals were grouped into quintiles by their risk-adjusted mortality rates. The investigators controlled 27 variables in the risk-adjustment model, including age, sex, race, and American Society of Anesthesiologists physical status classification. Risk-adjusted mortality rates ranged from 1.5% to 7.4% across the groups. Next, they compared complication rates for the nine common postoperative complications across the groups, as well as failure-to-rescue rates (i.e., rates of death caused by any of the nine postoperative complications).

A total of 51% of patients were female, and most (81%) were white, with a mean body mass index of 27 kg/m

High-mortality hospitals had a 1.5-fold greater risk of postsurgical complications: 16.2% in the high-mortality group, compared with 12.7% in the low-mortality group. “This cannot explain the nearly threefold mortality rate difference across our hospitals. However, when we looked at the failure-to-rescue rate, there's an astonishing difference,” he said.

“Many existing policies, which are aimed at reducing the incidence of complications, may not be able to reduce this observed variation in mortality. Rather, we may need to focus on the timely recognition and management of complications once they occur. The next step will be to develop a better understanding of the hospital resources and processes of care that lead to rescue from postsurgical complications.”

Dr. Ghaferi reported that he has no relevant financial relationships.

FORT MYERS, FLA. — The difference between successful and unsuccessful treatment of patients for postsurgical complications may help account for the wide variability in mortality rates following major surgery at hospitals nationwide, according to a retrospective study of data for more than 12,000 patients.

“High-mortality hospitals have mortality rates similar to those of low-mortality hospitals but markedly higher failure-to-rescue rates,” Dr. Amir A. Ghaferi said at the annual Academic Surgical Congress.

The failure-to-rescue rate (i.e., mortality following the development of a postsurgical complication) for high-mortality hospitals was more than twice that for low-mortality hospitals—26% versus 11%, respectively. “When we evaluated individual complications, this trend persisted,” said Dr. Ghaferi, a surgical resident at the University of Michigan, Ann Arbor.

Wide variability in mortality rates following major surgery has been noted previously. Dr. Ghaferi and his coinvestigators hypothesized that hospitals with higher mortality rates are less effective than low-mortality hospitals in rescuing patients, once they develop complications, and that this could account for some of the variability.

To test their hypothesis, they analyzed data from the American College of Surgeons' National Surgical Quality Improvement Program for all patients undergoing colectomy in 2005-2006. Data were available for 12,688 patients. Primary outcomes included 30-day mortality, the development of one of nine major postoperative complications (pneumonia, unplanned intubation, pulmonary embolism, myocardial infarction, acute renal failure, postoperative bleeding, deep wound infection, organ-space infection, and fascial dehiscence), and the mortality rates following each of these complications.

In all, 123 hospitals were grouped into quintiles by their risk-adjusted mortality rates. The investigators controlled 27 variables in the risk-adjustment model, including age, sex, race, and American Society of Anesthesiologists physical status classification. Risk-adjusted mortality rates ranged from 1.5% to 7.4% across the groups. Next, they compared complication rates for the nine common postoperative complications across the groups, as well as failure-to-rescue rates (i.e., rates of death caused by any of the nine postoperative complications).

A total of 51% of patients were female, and most (81%) were white, with a mean body mass index of 27 kg/m

High-mortality hospitals had a 1.5-fold greater risk of postsurgical complications: 16.2% in the high-mortality group, compared with 12.7% in the low-mortality group. “This cannot explain the nearly threefold mortality rate difference across our hospitals. However, when we looked at the failure-to-rescue rate, there's an astonishing difference,” he said.

“Many existing policies, which are aimed at reducing the incidence of complications, may not be able to reduce this observed variation in mortality. Rather, we may need to focus on the timely recognition and management of complications once they occur. The next step will be to develop a better understanding of the hospital resources and processes of care that lead to rescue from postsurgical complications.”

Dr. Ghaferi reported that he has no relevant financial relationships.

WASHINGTON — A clinical pathway involving early mobilization and an early switch from intravenous to oral antibiotics reduced the length of stay for patients with community-acquired pneumonia by more than 2 days, in a randomized study of 401 patients.

The median length of stay was significantly shorter for patients randomized to the clinical pathway, compared with those randomized to standard care—95 hours vs. 150 hours, Dr. Jordi Carratalà said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The use of the clinical pathway “was effective in reducing the duration of intravenous antibiotic therapy and length of stay without compromising patient outcomes,” said Dr. Carratalà of the infectious disease service at the Hospital Universitari de Bellvitge, Barcelona.

The first step of the clinical pathway was early mobilization. This involved getting the patient walking or at least sitting up for at least 20 minutes during the first 24 hours of hospitalization, with progressive periods of walking/sitting on successive days.

Then patients were switched from intravenous to oral antibiotics based on objective criteria. They were switched to oral antibiotics when they had a temperature no greater than 100° F (at two measurements at least 3 hours apart), showed improvement or resolution of symptoms, were able to maintain oral intake, and were hemodynamically stable; any comorbid conditions also had to be stable.

After patients were mobilized, on oral antibiotics, and stable, they were discharged.

A total of 401 immunocompetent adults diagnosed with community-acquired pneumonia (CAP) were randomized: 200 to conventional treatment and 201 to the clinical pathway. Patients with shock, aspiration pneumonia, or empyema were excluded. The patients in the two groups were similar in terms of demographic and baseline characteristics.

Streptococcus pneumoniae was the most commonly identified organism in both groups (85 patients in the intervention group and 79 in the control group). The causative organism was unknown in many cases in both groups as well (85 patients in the intervention group and 92 patients in the control group). Other identified organisms included Haemophilus influenzae and Legionella pneumophila.

The median duration of intravenous antibiotic therapy was also significantly shorter in the intervention group, compared with the controls (48 hours vs. 96 hours). A significantly lower percentage of the intervention group had adverse drug reactions, compared with the controls (4.5% vs. 16%). There were no differences between the two groups in terms of readmission rates or overall mortality.

“Switching from intravenous to oral therapy as soon as patients are clinically stable can reduce length of stay and lower the associated costs,” Dr. Carratalà said. However, the length of intravenous antibiotic use for the treatment of CAP varies widely, which prompted the researchers to undertake the trial.

WASHINGTON — A clinical pathway involving early mobilization and an early switch from intravenous to oral antibiotics reduced the length of stay for patients with community-acquired pneumonia by more than 2 days, in a randomized study of 401 patients.

The median length of stay was significantly shorter for patients randomized to the clinical pathway, compared with those randomized to standard care—95 hours vs. 150 hours, Dr. Jordi Carratalà said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The use of the clinical pathway “was effective in reducing the duration of intravenous antibiotic therapy and length of stay without compromising patient outcomes,” said Dr. Carratalà of the infectious disease service at the Hospital Universitari de Bellvitge, Barcelona.

The first step of the clinical pathway was early mobilization. This involved getting the patient walking or at least sitting up for at least 20 minutes during the first 24 hours of hospitalization, with progressive periods of walking/sitting on successive days.

Then patients were switched from intravenous to oral antibiotics based on objective criteria. They were switched to oral antibiotics when they had a temperature no greater than 100° F (at two measurements at least 3 hours apart), showed improvement or resolution of symptoms, were able to maintain oral intake, and were hemodynamically stable; any comorbid conditions also had to be stable.

After patients were mobilized, on oral antibiotics, and stable, they were discharged.

A total of 401 immunocompetent adults diagnosed with community-acquired pneumonia (CAP) were randomized: 200 to conventional treatment and 201 to the clinical pathway. Patients with shock, aspiration pneumonia, or empyema were excluded. The patients in the two groups were similar in terms of demographic and baseline characteristics.

Streptococcus pneumoniae was the most commonly identified organism in both groups (85 patients in the intervention group and 79 in the control group). The causative organism was unknown in many cases in both groups as well (85 patients in the intervention group and 92 patients in the control group). Other identified organisms included Haemophilus influenzae and Legionella pneumophila.

The median duration of intravenous antibiotic therapy was also significantly shorter in the intervention group, compared with the controls (48 hours vs. 96 hours). A significantly lower percentage of the intervention group had adverse drug reactions, compared with the controls (4.5% vs. 16%). There were no differences between the two groups in terms of readmission rates or overall mortality.

“Switching from intravenous to oral therapy as soon as patients are clinically stable can reduce length of stay and lower the associated costs,” Dr. Carratalà said. However, the length of intravenous antibiotic use for the treatment of CAP varies widely, which prompted the researchers to undertake the trial.

WASHINGTON — A clinical pathway involving early mobilization and an early switch from intravenous to oral antibiotics reduced the length of stay for patients with community-acquired pneumonia by more than 2 days, in a randomized study of 401 patients.

The median length of stay was significantly shorter for patients randomized to the clinical pathway, compared with those randomized to standard care—95 hours vs. 150 hours, Dr. Jordi Carratalà said at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

The use of the clinical pathway “was effective in reducing the duration of intravenous antibiotic therapy and length of stay without compromising patient outcomes,” said Dr. Carratalà of the infectious disease service at the Hospital Universitari de Bellvitge, Barcelona.

The first step of the clinical pathway was early mobilization. This involved getting the patient walking or at least sitting up for at least 20 minutes during the first 24 hours of hospitalization, with progressive periods of walking/sitting on successive days.

Then patients were switched from intravenous to oral antibiotics based on objective criteria. They were switched to oral antibiotics when they had a temperature no greater than 100° F (at two measurements at least 3 hours apart), showed improvement or resolution of symptoms, were able to maintain oral intake, and were hemodynamically stable; any comorbid conditions also had to be stable.

After patients were mobilized, on oral antibiotics, and stable, they were discharged.

A total of 401 immunocompetent adults diagnosed with community-acquired pneumonia (CAP) were randomized: 200 to conventional treatment and 201 to the clinical pathway. Patients with shock, aspiration pneumonia, or empyema were excluded. The patients in the two groups were similar in terms of demographic and baseline characteristics.

Streptococcus pneumoniae was the most commonly identified organism in both groups (85 patients in the intervention group and 79 in the control group). The causative organism was unknown in many cases in both groups as well (85 patients in the intervention group and 92 patients in the control group). Other identified organisms included Haemophilus influenzae and Legionella pneumophila.

The median duration of intravenous antibiotic therapy was also significantly shorter in the intervention group, compared with the controls (48 hours vs. 96 hours). A significantly lower percentage of the intervention group had adverse drug reactions, compared with the controls (4.5% vs. 16%). There were no differences between the two groups in terms of readmission rates or overall mortality.

“Switching from intravenous to oral therapy as soon as patients are clinically stable can reduce length of stay and lower the associated costs,” Dr. Carratalà said. However, the length of intravenous antibiotic use for the treatment of CAP varies widely, which prompted the researchers to undertake the trial.

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after the end of therapy) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% for those on vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens,” reported Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators.

The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., wholly owned subsidiary of Forrest. Dr. Corey disclosed receiving research funding and serving as an adviser to Cerexa.

The double-blind study randomized patients to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group—21% in the ceftaroline group and 25% in the vancomycin/aztreonam group—had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism. But ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See box.)

Most adverse events were mild—72% for both groups. The most common adverse event in the ceftaroline group was nausea (5.7%), followed by headache (5.1%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8.4%).

“Ceftaroline has the potential to provide a monotherapy option for the treatment of complicated skin and skin structure infections,” the investigators wrote.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after the end of therapy) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% for those on vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens,” reported Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators.

The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., wholly owned subsidiary of Forrest. Dr. Corey disclosed receiving research funding and serving as an adviser to Cerexa.

The double-blind study randomized patients to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group—21% in the ceftaroline group and 25% in the vancomycin/aztreonam group—had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism. But ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See box.)

Most adverse events were mild—72% for both groups. The most common adverse event in the ceftaroline group was nausea (5.7%), followed by headache (5.1%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8.4%).

“Ceftaroline has the potential to provide a monotherapy option for the treatment of complicated skin and skin structure infections,” the investigators wrote.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The investigational antibiotic ceftaroline was found to be effective against a range of gram-positive and gram-negative organisms that can cause complicated skin and skin structure infections, according to data from a phase III noninferiority study of more than 600 patients.

Clinical cure rates (8–15 days after the end of therapy) were similar for patients who received at least one dose of ceftaroline or vancomycin/aztreonam (the modified intent-to-treat population)—87% for those on ceftaroline and 86% for those on vancomycin-aztreonam, according to data from the CANVAS-1 study presented as a poster at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the annual meeting of the Infectious Diseases Society of America.

“Ceftaroline monotherapy was as effective and well tolerated as vancomycin plus aztreonam combination therapy in treating patients with complicated skin and skin structure infections due to both gram-positive and gram-negative pathogens,” reported Dr. Ralph Corey of Duke University, Durham, N.C., and his coinvestigators.

The study was supported by Forrest Laboratories Inc., which is developing ceftaroline. Two of Dr. Corey's coinvestigators are employed by Cerexa Inc., wholly owned subsidiary of Forrest. Dr. Corey disclosed receiving research funding and serving as an adviser to Cerexa.

The double-blind study randomized patients to either 600 mg intravenous ceftaroline every 12 hours for 5–14 days or 1 g intravenous vancomycin plus 1 g intravenous aztreonam (Azactam) every 12 hours for 5–14 days. Aztreonam was discontinued if gram-negative pathogens were not identified or suspected.

At enrollment, 353 patients were randomized to receive ceftaroline and 349 were randomized to receive vancomycin/aztreonam. The modified intention-to-treat population included all patients who had received any study drug—351 patients in the ceftaroline group and 347 patients in the vancomycin/aztreonam group.

Almost a quarter of the patients in each group—21% in the ceftaroline group and 25% in the vancomycin/aztreonam group—had polymicrobial infection. The most common infection type was deep, extensive cellulitis (35% in both groups), followed by major abscess (28% of the ceftaroline group and 29% of the vancomycin/aztreonam group).

There were 471 patients—244 in the ceftaroline group and 227 in the vancomycin/aztreonam group—who were microbiologically evaluable. Microbiologic eradication was achieved in 92% of patients on ceftaroline and 93% of patients on vancomycin/aztreonam.

Staphylococcus aureus was the most commonly isolated organism. But ceftaroline was effective against a range of gram-positive and gram-negative organisms. (See box.)

Most adverse events were mild—72% for both groups. The most common adverse event in the ceftaroline group was nausea (5.7%), followed by headache (5.1%). The most common adverse event in the vancomycin/aztreonam group was pruritus (8.4%).

“Ceftaroline has the potential to provide a monotherapy option for the treatment of complicated skin and skin structure infections,” the investigators wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

Vitamin D, skin cancer screening, and chemoprevention top the list of current melanoma prevention controversies, according to Dr. Clara Curiel-Lewandowski.

Vitamin D has been a contentious subject for many years with its being suggested that increased sun protection may be associated with lower vitamin D levels, noted Dr. Lewandowski at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

"A decrease in the serum level of vitamin D has been observed in the general population, particularly here in the United States.

"The challenge is to understand to which degree each modulating factor—such as vitamin D dietary intake, photoprotection, body mass index, and geographical location—contributes to the observed decline in serum levels," she said in an interview.

"There is no randomized prospective study linking vitamin D deficiency to excessive photoprotection. Those studies are very difficult to carry out," said Dr. Curiel-Lewandowski, who is director of the pigmented lesion clinic and multidisciplinary oncology at the Arizona Cancer Center in Tucson.

Another component in declining vitamin D levels is that humans produce less vitamin D as they age. Therefore, rising life expectancy may have a role in decreased vitamin D levels. "We're now living to 60, 70, 80 years and we are converting less vitamin D, irrespective of other sources," she said.

In addition, normal levels of serum 25(OH)D are now in the 70-nmol/L range, where it used to be 35–40 nmol/L, she said. With all of these variables, it is very difficult to tease out which of the components are responsible for declining vitamin D levels.

Advice to skin cancer patients about vitamin D should be based on common sense, said Dr. Curiel-Lewandowski.

She recommends that patients pursue a balanced diet, take daily vitamin D supplements above 400 IU if needed, and limit sun exposure to early morning and late afternoon hours. The specific dose supplementation for individuals with suspected risk factors for vitamin D deficiency should be based on their serum 25(OH)D levels.

Skin Cancer Screening

It's important to make the distinction between screening the general population and screening specific high-risk groups for skin cancer, said Dr. Curiel-Lewandowski.

"Cost effectiveness of massive skin cancer screening in the general population has been questioned," she said. An agreement needs to be reached on who is at risk for melanoma and how to target them for skin cancer screening.

The United States Preventive Services Task Force just released new recommendations on skin cancer screening for the general population (Ann. Intern. Med. 2009;150:188–93).

The task force said that there is insufficient evidence to recommend for or against skin cancer screening in the general population. (See story on pg. 4.)

"It is important to understand—no one is against skin cancer screening," said Dr. Curiel-Lewandowski. There simply are not enough data to recommend for or against it in the general population.

"In order to properly validate the effectiveness of massive or selective screening, randomized prospective studies will need to be completed. However, the incidence of melanoma is lower compared with other cancers and in order to get significance, you need more than 400,000 subjects involved and followed for over 10 years to achieve reasonable outcome data. … It's a very difficult study to accomplish," she said.

The task force did identify high-risk groups of individuals: fair-skinned men and women older than 65 years, patients with atypical nevi, patients with more than 50 nevi, and those with a family history of melanoma.

"What's not clear from this message is what to do with people that are known to be at high risk," she said, noting that the new recommendations identify these groups "but they don't tell you the type of screening and frequency that is recommended."

These are precisely the patients that many dermatologists see—patients with atypical nevi, those with a family history of melanoma, and transplant patients. Screenings should be done for these individuals, said Dr. Curiel-Lewandowski.

Chemoprevention

"The reason why the concept of melanoma chemoprevention is emerging is because new alternatives are necessary to decrease the burden of disease, especially in high risk individuals. This rationale is particularly compelling since we haven't been successful in decreasing mortality rates. … It opens up another option, which is trying to identify systemic agents that can be used in individuals at higher risk for melanoma to slow down the development of disease or even prevent it," Dr. Curiel-Lewandowski commented.

In the 1980s, studies were performed using topical retinoids for atypical nevi. In the late 1990s, statins became the hot topic. Neither option panned out. "What is emerging now among several candidate agents are nonsteroidal anti-inflammatories and green tea derivatives" she said.

The idea of using NSAIDs for the chemoprevention of melanoma comes from experimental and limited epidemiologic and clinical data suggesting that the extended use of NSAIDs decreases the risk of melanoma development. Ongoing larger epidemiologic studies looking in more detail at the strength of this association are expected to be released within the next year.

"Since multiple melanoma pathways have been identified, the effectiveness of a specific chemopreventive agent in a given high-risk population needs to be carefully thought out," Dr. Curiel-Lewandowski said.

Some have advanced this as an argument against chemoprevention.

SDEF and this newspaper are owned by Elsevier.

The U.S. Preventive Services Task Force still cannot recommend for or against whole-body skin examination by a primary care physician or by patient self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.

The task force concluded that there is not enough evidence to assess the benefits and harms from such examinations in its recommendations published in the Annals of Internal Medicine (2009;150:188–93).

The previous recommendation came in 2001, when the group also concluded that there was insufficient evidence to recommend for or against routine whole-body skin examination for skin cancer screening.

“This is not to say that studies have shown that it's not effective, what they're saying is that there are just no studies out there,” commented Dr. Darrell S. Rigel, a clinical professor of dermatology at New York University.

The task force did note two critical gaps in knowledge. First, there is insufficient evidence (a lack of studies) to determine whether early detection of skin cancer reduces morbidity or mortality from skin cancer. Second, there is insufficient evidence to determine the magnitude of harms from screening for skin cancer.

The task force found no randomized studies that examined whether screening by clinicians is associated with improved clinical outcomes. Screening appears to consistently identify thinner melanomas on the average than those found during usual care, the task force noted. However, it's not known whether the detection of the thinner lesions leads to decreased morbidity or mortality.

Based on the current review, the USPSTF noted that there is fair evidence that screening by clinicians is moderately accurate in detecting melanoma. They determined primary care physicians to be moderately accurate in diagnosing melanoma—with sensitivity ranging from 42%–100% and specificity ranging from 70%–98%.

“What I recommend to primary care physicians is to incorporate the screening as part of the full-body exam … the marginal cost is nothing,” said Dr. Rigel.

The task force noted that the recommendation applies only to the adult general population without a history of premalignant or malignant lesions. They did not assess the outcomes related to surveillance of patients at extremely high risk.

Primary care clinicians should be aware that fair-skinned men and women older than 65 years, patients with atypical moles, or those with more than 50 moles are groups that are known to be at a substantially increased risk for melanoma.

The task force urged primary care clinicians to remain alert for skin lesions with malignant features that are noted during physical examinations performed for other purposes. The ABCD criteria—asymmetry, border, color, and diameter—or rapidly changing lesions are features associated with an increased risk for cancer, they noted. Biopsy of suspected lesions is warranted.

The U.S. Preventive Services Task Force still cannot recommend for or against whole-body skin examination by a primary care physician or by patient self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.

The task force concluded that there is not enough evidence to assess the benefits and harms from such examinations in its recommendations published in the Annals of Internal Medicine (2009;150:188–93).

The previous recommendation came in 2001, when the group also concluded that there was insufficient evidence to recommend for or against routine whole-body skin examination for skin cancer screening.

“This is not to say that studies have shown that it's not effective, what they're saying is that there are just no studies out there,” commented Dr. Darrell S. Rigel, a clinical professor of dermatology at New York University.

The task force did note two critical gaps in knowledge. First, there is insufficient evidence (a lack of studies) to determine whether early detection of skin cancer reduces morbidity or mortality from skin cancer. Second, there is insufficient evidence to determine the magnitude of harms from screening for skin cancer.

The task force found no randomized studies that examined whether screening by clinicians is associated with improved clinical outcomes. Screening appears to consistently identify thinner melanomas on the average than those found during usual care, the task force noted. However, it's not known whether the detection of the thinner lesions leads to decreased morbidity or mortality.

Based on the current review, the USPSTF noted that there is fair evidence that screening by clinicians is moderately accurate in detecting melanoma. They determined primary care physicians to be moderately accurate in diagnosing melanoma—with sensitivity ranging from 42%–100% and specificity ranging from 70%–98%.

“What I recommend to primary care physicians is to incorporate the screening as part of the full-body exam … the marginal cost is nothing,” said Dr. Rigel.

The task force noted that the recommendation applies only to the adult general population without a history of premalignant or malignant lesions. They did not assess the outcomes related to surveillance of patients at extremely high risk.

Primary care clinicians should be aware that fair-skinned men and women older than 65 years, patients with atypical moles, or those with more than 50 moles are groups that are known to be at a substantially increased risk for melanoma.

The task force urged primary care clinicians to remain alert for skin lesions with malignant features that are noted during physical examinations performed for other purposes. The ABCD criteria—asymmetry, border, color, and diameter—or rapidly changing lesions are features associated with an increased risk for cancer, they noted. Biopsy of suspected lesions is warranted.

The U.S. Preventive Services Task Force still cannot recommend for or against whole-body skin examination by a primary care physician or by patient self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.

The task force concluded that there is not enough evidence to assess the benefits and harms from such examinations in its recommendations published in the Annals of Internal Medicine (2009;150:188–93).

The previous recommendation came in 2001, when the group also concluded that there was insufficient evidence to recommend for or against routine whole-body skin examination for skin cancer screening.

“This is not to say that studies have shown that it's not effective, what they're saying is that there are just no studies out there,” commented Dr. Darrell S. Rigel, a clinical professor of dermatology at New York University.

The task force did note two critical gaps in knowledge. First, there is insufficient evidence (a lack of studies) to determine whether early detection of skin cancer reduces morbidity or mortality from skin cancer. Second, there is insufficient evidence to determine the magnitude of harms from screening for skin cancer.

The task force found no randomized studies that examined whether screening by clinicians is associated with improved clinical outcomes. Screening appears to consistently identify thinner melanomas on the average than those found during usual care, the task force noted. However, it's not known whether the detection of the thinner lesions leads to decreased morbidity or mortality.

Based on the current review, the USPSTF noted that there is fair evidence that screening by clinicians is moderately accurate in detecting melanoma. They determined primary care physicians to be moderately accurate in diagnosing melanoma—with sensitivity ranging from 42%–100% and specificity ranging from 70%–98%.

“What I recommend to primary care physicians is to incorporate the screening as part of the full-body exam … the marginal cost is nothing,” said Dr. Rigel.

The task force noted that the recommendation applies only to the adult general population without a history of premalignant or malignant lesions. They did not assess the outcomes related to surveillance of patients at extremely high risk.

Primary care clinicians should be aware that fair-skinned men and women older than 65 years, patients with atypical moles, or those with more than 50 moles are groups that are known to be at a substantially increased risk for melanoma.

The task force urged primary care clinicians to remain alert for skin lesions with malignant features that are noted during physical examinations performed for other purposes. The ABCD criteria—asymmetry, border, color, and diameter—or rapidly changing lesions are features associated with an increased risk for cancer, they noted. Biopsy of suspected lesions is warranted.