Elizabeth Mechcatie

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report, based on national surveillance data between 2003 and 2008 (MMWR 2010;14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Previously, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008). The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

“Reversing the upward trend in CS rates will require collaboration among health care providers, health departments, health insurers, policy makers, and the public to reduce syphilis among women and to increase early prenatal care access and syphilis screening during pregnancy,” the report said.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in the CS rate in 2009 and in the future.

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report, based on national surveillance data between 2003 and 2008 (MMWR 2010;14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Previously, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008). The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

“Reversing the upward trend in CS rates will require collaboration among health care providers, health departments, health insurers, policy makers, and the public to reduce syphilis among women and to increase early prenatal care access and syphilis screening during pregnancy,” the report said.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in the CS rate in 2009 and in the future.

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report, based on national surveillance data between 2003 and 2008 (MMWR 2010;14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Previously, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008). The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

“Reversing the upward trend in CS rates will require collaboration among health care providers, health departments, health insurers, policy makers, and the public to reduce syphilis among women and to increase early prenatal care access and syphilis screening during pregnancy,” the report said.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in the CS rate in 2009 and in the future.

The Food and Drug Administration approved a thermal device that ablates airway smooth muscle to treat severe, persistent asthma that is not well controlled with medication alone.

The device uses a radiofrequency (RF) generator and a single-use catheter with an electrode basket at the tip to deliver RF energy to the airway wall to reduce smooth muscle. The procedure is performed as outpatient bronchoscopy.

Asthmatx Inc. will market the device as the Alair Bronchial Thermoplasty System. The thermoplasty system is the first medical device to use RF energy to treat severe and persistent asthma “in certain adults,” according to the FDA statement announcing the April 27 approval.

The RF energy “heats the lung tissue in a controlled manner, reducing the thickness of smooth muscle in the airways and improving a patient's ability to breathe,” the FDA statement noted, adding that multiple treatment sessions to target different parts of the lungs are required for patients to benefit from treatment.

The FDA based its approval decision on a randomized, double-blind, controlled trial of 297 patients with severe, persistent asthma who experienced symptoms despite treatment with inhaled corticosteroids and long-acting beta agonists (Am. J. Respir. Crit. Care Med. 2010;181:116–24).

In that study, patients treated with the Alair system had improvements in asthma-specific quality of life and a reduction in severe exacerbations, as well as improvements in asthma-related quality of life.

Possible side effects during treatment include chest tightness or pain, atelectasis, hemoptysis, anxiety, headaches, and nausea. Other risks associated with treatment include acute asthma attacks and wheezing, according to the FDA statement.

The FDA also noted that the device is designed to reduce the number of severe asthma attacks on a long-term basis.

As a condition of approval, the FDA will require Asthmatx to conduct a 5-year postmarketing study to evaluate the long-term safety and effectiveness of the device.

That requirement reflects concerns by an FDA advisory panel that reviewed the device in October 2009. The panel agreed that there was reasonable evidence that the device was safe and effective, and it recommended approval. However, panel members recommended a postmarketing study to assess the device's long-term safety and efficacy.

For that postmarketing study, Asthmatx will enroll many of the patients who were enrolled in the clinical trial, as well as 300 new patients in the United States, according to the FDA.

Patients with asthma who have an implantable electronic device, such as a pacemaker, and those who are known to be sensitive to lidocaine, atropine, or benzodiazepines should not be treated with the thermal device, according to the FDA.

In addition, the procedure should not be performed in asthma patients who have an active respiratory infection or coagulopathy, or in those who are having an asthma exacerbation and those who have had changes to their corticosteroid regimen within 14 days prior to treatment.

In addition, areas of the lung that have been treated with the device should not be retreated, according to the FDA.

The Food and Drug Administration approved a thermal device that ablates airway smooth muscle to treat severe, persistent asthma that is not well controlled with medication alone.

The device uses a radiofrequency (RF) generator and a single-use catheter with an electrode basket at the tip to deliver RF energy to the airway wall to reduce smooth muscle. The procedure is performed as outpatient bronchoscopy.

Asthmatx Inc. will market the device as the Alair Bronchial Thermoplasty System. The thermoplasty system is the first medical device to use RF energy to treat severe and persistent asthma “in certain adults,” according to the FDA statement announcing the April 27 approval.

The RF energy “heats the lung tissue in a controlled manner, reducing the thickness of smooth muscle in the airways and improving a patient's ability to breathe,” the FDA statement noted, adding that multiple treatment sessions to target different parts of the lungs are required for patients to benefit from treatment.

The FDA based its approval decision on a randomized, double-blind, controlled trial of 297 patients with severe, persistent asthma who experienced symptoms despite treatment with inhaled corticosteroids and long-acting beta agonists (Am. J. Respir. Crit. Care Med. 2010;181:116–24).

In that study, patients treated with the Alair system had improvements in asthma-specific quality of life and a reduction in severe exacerbations, as well as improvements in asthma-related quality of life.

Possible side effects during treatment include chest tightness or pain, atelectasis, hemoptysis, anxiety, headaches, and nausea. Other risks associated with treatment include acute asthma attacks and wheezing, according to the FDA statement.

The FDA also noted that the device is designed to reduce the number of severe asthma attacks on a long-term basis.

As a condition of approval, the FDA will require Asthmatx to conduct a 5-year postmarketing study to evaluate the long-term safety and effectiveness of the device.

That requirement reflects concerns by an FDA advisory panel that reviewed the device in October 2009. The panel agreed that there was reasonable evidence that the device was safe and effective, and it recommended approval. However, panel members recommended a postmarketing study to assess the device's long-term safety and efficacy.

For that postmarketing study, Asthmatx will enroll many of the patients who were enrolled in the clinical trial, as well as 300 new patients in the United States, according to the FDA.

Patients with asthma who have an implantable electronic device, such as a pacemaker, and those who are known to be sensitive to lidocaine, atropine, or benzodiazepines should not be treated with the thermal device, according to the FDA.

In addition, the procedure should not be performed in asthma patients who have an active respiratory infection or coagulopathy, or in those who are having an asthma exacerbation and those who have had changes to their corticosteroid regimen within 14 days prior to treatment.

In addition, areas of the lung that have been treated with the device should not be retreated, according to the FDA.

The Food and Drug Administration approved a thermal device that ablates airway smooth muscle to treat severe, persistent asthma that is not well controlled with medication alone.

The device uses a radiofrequency (RF) generator and a single-use catheter with an electrode basket at the tip to deliver RF energy to the airway wall to reduce smooth muscle. The procedure is performed as outpatient bronchoscopy.

Asthmatx Inc. will market the device as the Alair Bronchial Thermoplasty System. The thermoplasty system is the first medical device to use RF energy to treat severe and persistent asthma “in certain adults,” according to the FDA statement announcing the April 27 approval.

The RF energy “heats the lung tissue in a controlled manner, reducing the thickness of smooth muscle in the airways and improving a patient's ability to breathe,” the FDA statement noted, adding that multiple treatment sessions to target different parts of the lungs are required for patients to benefit from treatment.

The FDA based its approval decision on a randomized, double-blind, controlled trial of 297 patients with severe, persistent asthma who experienced symptoms despite treatment with inhaled corticosteroids and long-acting beta agonists (Am. J. Respir. Crit. Care Med. 2010;181:116–24).

In that study, patients treated with the Alair system had improvements in asthma-specific quality of life and a reduction in severe exacerbations, as well as improvements in asthma-related quality of life.

Possible side effects during treatment include chest tightness or pain, atelectasis, hemoptysis, anxiety, headaches, and nausea. Other risks associated with treatment include acute asthma attacks and wheezing, according to the FDA statement.

The FDA also noted that the device is designed to reduce the number of severe asthma attacks on a long-term basis.

As a condition of approval, the FDA will require Asthmatx to conduct a 5-year postmarketing study to evaluate the long-term safety and effectiveness of the device.

That requirement reflects concerns by an FDA advisory panel that reviewed the device in October 2009. The panel agreed that there was reasonable evidence that the device was safe and effective, and it recommended approval. However, panel members recommended a postmarketing study to assess the device's long-term safety and efficacy.

For that postmarketing study, Asthmatx will enroll many of the patients who were enrolled in the clinical trial, as well as 300 new patients in the United States, according to the FDA.

Patients with asthma who have an implantable electronic device, such as a pacemaker, and those who are known to be sensitive to lidocaine, atropine, or benzodiazepines should not be treated with the thermal device, according to the FDA.

In addition, the procedure should not be performed in asthma patients who have an active respiratory infection or coagulopathy, or in those who are having an asthma exacerbation and those who have had changes to their corticosteroid regimen within 14 days prior to treatment.

In addition, areas of the lung that have been treated with the device should not be retreated, according to the FDA.

Severe liver injuries have been associated with use of the antithyroid drug propylthiouracil, and the Food and Drug Administration has added a boxed warning to the product's label conveying this risk, the agency announced.

The warning for propylthiouracil (PTU) says that there have been reports of severe liver injury and acute liver failure—including fatalities—in adults and children who've been treated with the drug.

The warning also includes a statement concerning preferential prescribing of the drug for patients in early pregnancy. The warning notes that because birth defects have been associated with use of the antithyroid drug methimazole during the first trimester, “propylthiouracil may be the treatment of choice during and just before the first trimester of pregnancy.”

Information about PTU use during early pregnancy was based on a review of postmarketing data on PTU and methimazole. The review indicated that reports of congenital malformations were about threefold greater with methimazole than PTU, and there was a “distinct and consistent” pattern of congenital malformations associated with methimazole but not PTU.

Serious adverse events associated with PTU should be reported to the FDA at www.fda.gov/medwatch

Severe liver injuries have been associated with use of the antithyroid drug propylthiouracil, and the Food and Drug Administration has added a boxed warning to the product's label conveying this risk, the agency announced.

The warning for propylthiouracil (PTU) says that there have been reports of severe liver injury and acute liver failure—including fatalities—in adults and children who've been treated with the drug.

The warning also includes a statement concerning preferential prescribing of the drug for patients in early pregnancy. The warning notes that because birth defects have been associated with use of the antithyroid drug methimazole during the first trimester, “propylthiouracil may be the treatment of choice during and just before the first trimester of pregnancy.”

Information about PTU use during early pregnancy was based on a review of postmarketing data on PTU and methimazole. The review indicated that reports of congenital malformations were about threefold greater with methimazole than PTU, and there was a “distinct and consistent” pattern of congenital malformations associated with methimazole but not PTU.

Serious adverse events associated with PTU should be reported to the FDA at www.fda.gov/medwatch

Severe liver injuries have been associated with use of the antithyroid drug propylthiouracil, and the Food and Drug Administration has added a boxed warning to the product's label conveying this risk, the agency announced.

The warning for propylthiouracil (PTU) says that there have been reports of severe liver injury and acute liver failure—including fatalities—in adults and children who've been treated with the drug.

The warning also includes a statement concerning preferential prescribing of the drug for patients in early pregnancy. The warning notes that because birth defects have been associated with use of the antithyroid drug methimazole during the first trimester, “propylthiouracil may be the treatment of choice during and just before the first trimester of pregnancy.”

Information about PTU use during early pregnancy was based on a review of postmarketing data on PTU and methimazole. The review indicated that reports of congenital malformations were about threefold greater with methimazole than PTU, and there was a “distinct and consistent” pattern of congenital malformations associated with methimazole but not PTU.

Serious adverse events associated with PTU should be reported to the FDA at www.fda.gov/medwatch

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on H.P. Acthar gel, an injectable formulation of adrenocorticotropin hormone, provided sufficient evidence that it was a safe and effective treatment for infantile spasms.

In early May, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee panel voted 22 to 1 that the data on Acthar provided “substantial” evidence that it was an effective treatment of infantile spasms (IS). The panel also voted 20 to 1, with 2 abstentions, that the manufacturer, Questcor Pharmaceuticals Inc., had provided enough evidence that Acthar was safe at a dosing regimen that was considered effective. However, they noted that there were significant risks associated with treatment and that some remaining issues about the treatment needed further study, including whether dosing regimens other than the one proposed by the company should be investigated. The panel was not specifically asked to vote on whether to recommend approval for the IS indication.

If approved, Acthar (repository corticotropin injection) would join vigabatrin (Sabril) as the second FDA-approved treatment for IS, a severe, rare form of epilepsy that affects about 2,000 children in the United States every year, usually appearing at age 3–7 months. Acthar has been used off-label to treat IS since the late 1950s and is recognized as a treatment for IS by the American Academy of Neurology. Prednisone is also used off-label to treat IS.

Questcor reanalyzed data from three published randomized controlled studies, using the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response) to evaluate the efficacy of Acthar at a dosage regimen of 150 U/m

In the primary study, published in 1996, 13 of the 15 (87%) infants treated with Acthar had an overall response, compared with 4 of the 14 (29%) treated with prednisone (2 mg/kg per day in two divided doses), a significant difference.

The panel recommended making it clear to clinicians that the main study was small and that patients treated should be closely monitored for adverse effects of treatment, particularly adrenal insufficiency. The company also should analyze the relapse rate in patients who respond to treatment, for which there are scant data.

The FDA usually follows the recommendations of its advisory panels. One panelist with a conflict of interest was granted a waiver by the FDA.

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on H.P. Acthar gel, an injectable formulation of adrenocorticotropin hormone, provided sufficient evidence that it was a safe and effective treatment for infantile spasms.

In early May, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee panel voted 22 to 1 that the data on Acthar provided “substantial” evidence that it was an effective treatment of infantile spasms (IS). The panel also voted 20 to 1, with 2 abstentions, that the manufacturer, Questcor Pharmaceuticals Inc., had provided enough evidence that Acthar was safe at a dosing regimen that was considered effective. However, they noted that there were significant risks associated with treatment and that some remaining issues about the treatment needed further study, including whether dosing regimens other than the one proposed by the company should be investigated. The panel was not specifically asked to vote on whether to recommend approval for the IS indication.

If approved, Acthar (repository corticotropin injection) would join vigabatrin (Sabril) as the second FDA-approved treatment for IS, a severe, rare form of epilepsy that affects about 2,000 children in the United States every year, usually appearing at age 3–7 months. Acthar has been used off-label to treat IS since the late 1950s and is recognized as a treatment for IS by the American Academy of Neurology. Prednisone is also used off-label to treat IS.

Questcor reanalyzed data from three published randomized controlled studies, using the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response) to evaluate the efficacy of Acthar at a dosage regimen of 150 U/m

In the primary study, published in 1996, 13 of the 15 (87%) infants treated with Acthar had an overall response, compared with 4 of the 14 (29%) treated with prednisone (2 mg/kg per day in two divided doses), a significant difference.

The panel recommended making it clear to clinicians that the main study was small and that patients treated should be closely monitored for adverse effects of treatment, particularly adrenal insufficiency. The company also should analyze the relapse rate in patients who respond to treatment, for which there are scant data.

The FDA usually follows the recommendations of its advisory panels. One panelist with a conflict of interest was granted a waiver by the FDA.

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on H.P. Acthar gel, an injectable formulation of adrenocorticotropin hormone, provided sufficient evidence that it was a safe and effective treatment for infantile spasms.

In early May, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee panel voted 22 to 1 that the data on Acthar provided “substantial” evidence that it was an effective treatment of infantile spasms (IS). The panel also voted 20 to 1, with 2 abstentions, that the manufacturer, Questcor Pharmaceuticals Inc., had provided enough evidence that Acthar was safe at a dosing regimen that was considered effective. However, they noted that there were significant risks associated with treatment and that some remaining issues about the treatment needed further study, including whether dosing regimens other than the one proposed by the company should be investigated. The panel was not specifically asked to vote on whether to recommend approval for the IS indication.

If approved, Acthar (repository corticotropin injection) would join vigabatrin (Sabril) as the second FDA-approved treatment for IS, a severe, rare form of epilepsy that affects about 2,000 children in the United States every year, usually appearing at age 3–7 months. Acthar has been used off-label to treat IS since the late 1950s and is recognized as a treatment for IS by the American Academy of Neurology. Prednisone is also used off-label to treat IS.

Questcor reanalyzed data from three published randomized controlled studies, using the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response) to evaluate the efficacy of Acthar at a dosage regimen of 150 U/m

In the primary study, published in 1996, 13 of the 15 (87%) infants treated with Acthar had an overall response, compared with 4 of the 14 (29%) treated with prednisone (2 mg/kg per day in two divided doses), a significant difference.

The panel recommended making it clear to clinicians that the main study was small and that patients treated should be closely monitored for adverse effects of treatment, particularly adrenal insufficiency. The company also should analyze the relapse rate in patients who respond to treatment, for which there are scant data.

The FDA usually follows the recommendations of its advisory panels. One panelist with a conflict of interest was granted a waiver by the FDA.

Counseling teenage girls with systemic lupus erythematosus about contraception “is a critical part” of caring for this group of patients.

Ensuring that they have access to effective contraception is “crucial” for those who are sexually active, according to a review article on contraceptive choices for this patient population that was published in Pediatric Rheumatology.

Many adolescent girls with systemic lupus erythematosus (SLE) see their pediatric rheumatologist more often than they see their primary care physician.

If they are sexually active, then they—like other teenage girls in the United States—are at a high risk of unplanned pregnancy.

In general, all women with lupus are at a greater risk of worsening disease during pregnancy and have a greater risk of developing obstetric and fetal complications, compared with healthy women. Moreover, many of the medications used in lupus treatment are teratogens or abortifacients, so “practitioners must expend extra effort to help these patients avoid unplanned pregnancy,” the authors wrote (Pediatr. Rheumatol. Online 2010;8:10).

To provide the best possible care for this population, pediatric rheumatologists need to be comfortable discussing contraception and be knowledgeable about contraceptives, noted Dr. Melissa S. Tesher of the department of pediatrics at the University of Chicago and her colleagues.

The investigators didn't recommend any one option over another for this group of patients. “No contraceptive method is ideal,” they wrote, adding, “the risk of a given contraceptive must be balanced against the known significant risks of pregnancy in an adolescent with lupus.”

In an interview, Dr. Tesher said that pediatric rheumatologists should discuss these issues with their teenage patients, and encourage sexually active teens to use a highly effective form of contraception.

Although some of the newer, longer-acting contraceptives are good choices for this group, the contraceptive method should be chosen on a patient-by-patient basis, with the patient's participation, said Dr. Tesher, who decided to research and write the article with her colleagues after two teenaged lupus patients at the university clinic unexpectedly became pregnant.

If the pediatric rheumatologist doesn't bring up the issue of contraception, “it may not be addressed at all,” she said, adding that the comfort level in this area varies, partly because there are not many studies indicating what contraceptives are best for teenagers with lupus.

“It's not comparing the risk of taking the contraceptive vs. the risk of not taking the contraceptive; it's the risk to the patient from pregnancy and the risk of flare, and the risk of complications during pregnancy [that] tend to be very high in this group of patients.”

Although the investigators recommend condoms for protection against sexually transmitted infections, condoms and other barrier methods are not used consistently among adolescents and have high failure rates, so a second method should also be recommended.

The safety of estrogen-based oral contraceptives (OCs) in women with lupus is unclear. These agents have some benefits, but “OCs are not usually the best choice for a teen with lupus,” because it is not entirely clear whether exogenous estrogen increases the risk of lupus flares, Dr. Tesher commented in the interview.

“But there definitely is a risk of thrombosis in patients with antiphospholipid antibodies, and there are issues with OCs and adherence in teens,” she added.

Considering the documented thrombotic risks of estrogen-containing contraceptives, estrogen-free methods of birth control “are likely a more prudent choice in patients with other prothrombotic risk factors,” according to the article. These options include the progestin-only OC, which “is unlikely to worsen lupus activity or promote thrombosis,” but which has a high discontinuation rate among teens, the investigators noted.

The authors describe depot medroxyprogesterone acetate (DMPA), a widely available and cheap progestin-only method that is injected once every 3 months, as “a reasonable choice for many adolescents.” But the irregular periods and weight gain associated with DMPA are drawbacks, and long-term use is associated with reductions in bone mineral density, a concern for women with SLE who are already at an increased risk of osteopenia because of their disease and corticosteroid use, they wrote.

A relatively new option, Implanon, a single implantable rod that releases etonogestrel, “could be an excellent choice for some young women with SLE,” they said. There are no studies of the agent in women with lupus. The continuation rates among adolescent users are unknown, and Implanon use is often associated with irregular menstrual periods. However, the agent is highly effective for 3 years, is easily removed and rapidly reversible, and “does not appear to have a detrimental effect on bone density,” they wrote.

Intrauterine devices (IUDs) are also highly effective, easily reversible, long-term contraceptives, and “offer many potential advantages to women with SLE,” the authors said. There are limited data available on IUD safety in women with lupus. Data on the associated risk of pelvic inflammatory disease in another immunosuppressed population (HIV-infected women) are “encouraging.” The investigators concluded that “existing evidence does not support the opinion that a diagnosis of lupus or immunocompromise are contraindications to the use of an IUD.”

The levonorgestrel-releasing IUD, marketed as Mirena, “may be a better choice,” than the copper IUD, which is often associated with menorrhagia, as anemia is common among adolescents with SLE, they added.

Finally, the authors said that educating adolescents about and providing a prescription for emergency contraception (oral levonorgestrel), which is available without a prescription for people aged 17 and older, “are also appropriate in many circumstances.”

Disclosures: The authors had no financial conflicts to disclose.

Counseling teenage girls with systemic lupus erythematosus about contraception “is a critical part” of caring for this group of patients.

Ensuring that they have access to effective contraception is “crucial” for those who are sexually active, according to a review article on contraceptive choices for this patient population that was published in Pediatric Rheumatology.

Many adolescent girls with systemic lupus erythematosus (SLE) see their pediatric rheumatologist more often than they see their primary care physician.

If they are sexually active, then they—like other teenage girls in the United States—are at a high risk of unplanned pregnancy.

In general, all women with lupus are at a greater risk of worsening disease during pregnancy and have a greater risk of developing obstetric and fetal complications, compared with healthy women. Moreover, many of the medications used in lupus treatment are teratogens or abortifacients, so “practitioners must expend extra effort to help these patients avoid unplanned pregnancy,” the authors wrote (Pediatr. Rheumatol. Online 2010;8:10).

To provide the best possible care for this population, pediatric rheumatologists need to be comfortable discussing contraception and be knowledgeable about contraceptives, noted Dr. Melissa S. Tesher of the department of pediatrics at the University of Chicago and her colleagues.

The investigators didn't recommend any one option over another for this group of patients. “No contraceptive method is ideal,” they wrote, adding, “the risk of a given contraceptive must be balanced against the known significant risks of pregnancy in an adolescent with lupus.”

In an interview, Dr. Tesher said that pediatric rheumatologists should discuss these issues with their teenage patients, and encourage sexually active teens to use a highly effective form of contraception.

Although some of the newer, longer-acting contraceptives are good choices for this group, the contraceptive method should be chosen on a patient-by-patient basis, with the patient's participation, said Dr. Tesher, who decided to research and write the article with her colleagues after two teenaged lupus patients at the university clinic unexpectedly became pregnant.

If the pediatric rheumatologist doesn't bring up the issue of contraception, “it may not be addressed at all,” she said, adding that the comfort level in this area varies, partly because there are not many studies indicating what contraceptives are best for teenagers with lupus.

“It's not comparing the risk of taking the contraceptive vs. the risk of not taking the contraceptive; it's the risk to the patient from pregnancy and the risk of flare, and the risk of complications during pregnancy [that] tend to be very high in this group of patients.”

Although the investigators recommend condoms for protection against sexually transmitted infections, condoms and other barrier methods are not used consistently among adolescents and have high failure rates, so a second method should also be recommended.

The safety of estrogen-based oral contraceptives (OCs) in women with lupus is unclear. These agents have some benefits, but “OCs are not usually the best choice for a teen with lupus,” because it is not entirely clear whether exogenous estrogen increases the risk of lupus flares, Dr. Tesher commented in the interview.

“But there definitely is a risk of thrombosis in patients with antiphospholipid antibodies, and there are issues with OCs and adherence in teens,” she added.

Considering the documented thrombotic risks of estrogen-containing contraceptives, estrogen-free methods of birth control “are likely a more prudent choice in patients with other prothrombotic risk factors,” according to the article. These options include the progestin-only OC, which “is unlikely to worsen lupus activity or promote thrombosis,” but which has a high discontinuation rate among teens, the investigators noted.

The authors describe depot medroxyprogesterone acetate (DMPA), a widely available and cheap progestin-only method that is injected once every 3 months, as “a reasonable choice for many adolescents.” But the irregular periods and weight gain associated with DMPA are drawbacks, and long-term use is associated with reductions in bone mineral density, a concern for women with SLE who are already at an increased risk of osteopenia because of their disease and corticosteroid use, they wrote.

A relatively new option, Implanon, a single implantable rod that releases etonogestrel, “could be an excellent choice for some young women with SLE,” they said. There are no studies of the agent in women with lupus. The continuation rates among adolescent users are unknown, and Implanon use is often associated with irregular menstrual periods. However, the agent is highly effective for 3 years, is easily removed and rapidly reversible, and “does not appear to have a detrimental effect on bone density,” they wrote.

Intrauterine devices (IUDs) are also highly effective, easily reversible, long-term contraceptives, and “offer many potential advantages to women with SLE,” the authors said. There are limited data available on IUD safety in women with lupus. Data on the associated risk of pelvic inflammatory disease in another immunosuppressed population (HIV-infected women) are “encouraging.” The investigators concluded that “existing evidence does not support the opinion that a diagnosis of lupus or immunocompromise are contraindications to the use of an IUD.”

The levonorgestrel-releasing IUD, marketed as Mirena, “may be a better choice,” than the copper IUD, which is often associated with menorrhagia, as anemia is common among adolescents with SLE, they added.

Finally, the authors said that educating adolescents about and providing a prescription for emergency contraception (oral levonorgestrel), which is available without a prescription for people aged 17 and older, “are also appropriate in many circumstances.”

Disclosures: The authors had no financial conflicts to disclose.

Counseling teenage girls with systemic lupus erythematosus about contraception “is a critical part” of caring for this group of patients.

Ensuring that they have access to effective contraception is “crucial” for those who are sexually active, according to a review article on contraceptive choices for this patient population that was published in Pediatric Rheumatology.

Many adolescent girls with systemic lupus erythematosus (SLE) see their pediatric rheumatologist more often than they see their primary care physician.

If they are sexually active, then they—like other teenage girls in the United States—are at a high risk of unplanned pregnancy.

In general, all women with lupus are at a greater risk of worsening disease during pregnancy and have a greater risk of developing obstetric and fetal complications, compared with healthy women. Moreover, many of the medications used in lupus treatment are teratogens or abortifacients, so “practitioners must expend extra effort to help these patients avoid unplanned pregnancy,” the authors wrote (Pediatr. Rheumatol. Online 2010;8:10).

To provide the best possible care for this population, pediatric rheumatologists need to be comfortable discussing contraception and be knowledgeable about contraceptives, noted Dr. Melissa S. Tesher of the department of pediatrics at the University of Chicago and her colleagues.

The investigators didn't recommend any one option over another for this group of patients. “No contraceptive method is ideal,” they wrote, adding, “the risk of a given contraceptive must be balanced against the known significant risks of pregnancy in an adolescent with lupus.”

In an interview, Dr. Tesher said that pediatric rheumatologists should discuss these issues with their teenage patients, and encourage sexually active teens to use a highly effective form of contraception.

Although some of the newer, longer-acting contraceptives are good choices for this group, the contraceptive method should be chosen on a patient-by-patient basis, with the patient's participation, said Dr. Tesher, who decided to research and write the article with her colleagues after two teenaged lupus patients at the university clinic unexpectedly became pregnant.

If the pediatric rheumatologist doesn't bring up the issue of contraception, “it may not be addressed at all,” she said, adding that the comfort level in this area varies, partly because there are not many studies indicating what contraceptives are best for teenagers with lupus.

“It's not comparing the risk of taking the contraceptive vs. the risk of not taking the contraceptive; it's the risk to the patient from pregnancy and the risk of flare, and the risk of complications during pregnancy [that] tend to be very high in this group of patients.”

Although the investigators recommend condoms for protection against sexually transmitted infections, condoms and other barrier methods are not used consistently among adolescents and have high failure rates, so a second method should also be recommended.

The safety of estrogen-based oral contraceptives (OCs) in women with lupus is unclear. These agents have some benefits, but “OCs are not usually the best choice for a teen with lupus,” because it is not entirely clear whether exogenous estrogen increases the risk of lupus flares, Dr. Tesher commented in the interview.

“But there definitely is a risk of thrombosis in patients with antiphospholipid antibodies, and there are issues with OCs and adherence in teens,” she added.

Considering the documented thrombotic risks of estrogen-containing contraceptives, estrogen-free methods of birth control “are likely a more prudent choice in patients with other prothrombotic risk factors,” according to the article. These options include the progestin-only OC, which “is unlikely to worsen lupus activity or promote thrombosis,” but which has a high discontinuation rate among teens, the investigators noted.

The authors describe depot medroxyprogesterone acetate (DMPA), a widely available and cheap progestin-only method that is injected once every 3 months, as “a reasonable choice for many adolescents.” But the irregular periods and weight gain associated with DMPA are drawbacks, and long-term use is associated with reductions in bone mineral density, a concern for women with SLE who are already at an increased risk of osteopenia because of their disease and corticosteroid use, they wrote.

A relatively new option, Implanon, a single implantable rod that releases etonogestrel, “could be an excellent choice for some young women with SLE,” they said. There are no studies of the agent in women with lupus. The continuation rates among adolescent users are unknown, and Implanon use is often associated with irregular menstrual periods. However, the agent is highly effective for 3 years, is easily removed and rapidly reversible, and “does not appear to have a detrimental effect on bone density,” they wrote.

Intrauterine devices (IUDs) are also highly effective, easily reversible, long-term contraceptives, and “offer many potential advantages to women with SLE,” the authors said. There are limited data available on IUD safety in women with lupus. Data on the associated risk of pelvic inflammatory disease in another immunosuppressed population (HIV-infected women) are “encouraging.” The investigators concluded that “existing evidence does not support the opinion that a diagnosis of lupus or immunocompromise are contraindications to the use of an IUD.”

The levonorgestrel-releasing IUD, marketed as Mirena, “may be a better choice,” than the copper IUD, which is often associated with menorrhagia, as anemia is common among adolescents with SLE, they added.

Finally, the authors said that educating adolescents about and providing a prescription for emergency contraception (oral levonorgestrel), which is available without a prescription for people aged 17 and older, “are also appropriate in many circumstances.”

Disclosures: The authors had no financial conflicts to disclose.

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR 2010; 14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.)

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (from 12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (from 1.3 to 2.8 cases per 100,000 live births).

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR 2010; 14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.)

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (from 12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (from 1.3 to 2.8 cases per 100,000 live births).

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR 2010; 14:413–7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.)

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (from 12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (from 1.3 to 2.8 cases per 100,000 live births).

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

The use of Rotarix can be resumed and the use of RotaTeq continued because there is no evidence that the porcine virus detected in both rotavirus vaccines poses a safety risk to humans, according to the Food and Drug Administration.

The FDA based its decision on laboratory results from the manufacturers of the two rotavirus vaccines and from FDA laboratories, on a scientific literature review, and on input from scientific and public health experts, according to a statement issued by the agency on May 14. In addition, the agency does not believe a medical follow-up is needed for children who have been vaccinated with these vaccines.

Those experts include the FDA's Vaccines and Related Biological Products Advisory Committee, which met a week before the agency announcement to discuss the recent identification of porcine circovirus (PCV) type 1 DNA in GlaxoSmithKline's rotavirus vaccine, Rotarix, which resulted in the FDA's recommendation to temporarily suspend the use of Rotarix on March 22. At the recent meeting, the FDA announced that PCV has also been detected in Merck & Co.'s rotavirus vaccine, RotaTeq.

In addition, the panel agreed that the benefits of the two rotavirus vaccines greatly outweighed the theoretical risk that the detection of PCV in the vaccines could cause human infection, but recommended more study of this potential risk.

Panelists generally agreed that they were encouraged by the available data that did not indicate that PCV detected in the vaccines caused human infection, but noted that this had not yet been proved. Among the panel's recommendations for further studies were serology studies of children with cystic fibrosis on long-term pancreatic enzyme supplementation to check for evidence of antibodies to PCV. (Pancreatic enzyme supplements are derived from the pancreas of pigs, where PCV is detected.)

When the temporary suspension of Rotarix use was announced in March, the FDA said that PCV1 DNA had not been found in RotaTeq, but recommended that Merck conduct tests. At the meeting, Dr. Norman Baylor, the director of the FDA's Office of Vaccines Research and Review, told the panel that at the May meeting, Merck had informed the agency that fragments of DNA from PCV type 1 and type 2 have been identified in the vaccine in preliminary studies. But no recommendation to suspend the use of this vaccine was made at that time.

PCV is common among pigs but is not known to cause disease in humans. There is currently no evidence that PCV in rotavirus vaccines licensed in the United States pose a human safety risk, according to Dr. Baylor. In a statement issued late on May 6, Merck said that the levels of PCV DNA detected in RotaTeq were “very low,” and that “there is no evidence at this time that DNA from PCV causes any disease in humans.”

At the meeting, GSK presented results of studies conducted since PCV DNA was detected in Rotarix, which has not provided any evidence that PCV1 in Rotarix causes infections in humans, according to the presenters. The company tested stool and blood samples taken from vaccine recipients in four Rotarix clinical trials conducted in Africa, Asia, Latin America, and Europe, which included three studies of healthy infants and one of HIV-positive infants. Overall, PCV1 DNA was detected in the stool of four infants, on the third day after vaccination, which the company said was suggestive of “transient passage” of the PCV DNA through the GI tract, but none of these infants or any other infants in the trials had evidence of antibodies to PCV1 in blood samples that had been taken after they received the last vaccine dose, according to GSK.

The FDA and the companies are continuing to conduct studies.

“We have data to suggest this virus is probably not pathogenic in humans,” said panelist Dr. Jos Romero, chief, pediatric infectious diseases, Arkansas Children's Hospital, Little Rock. “Whether it can infect humans still remains a question, but it looks like it doesn't cause disease,” added Dr. Romero, who, like other panelists, said that more studies are definitely needed. He and others agreed that this should include more research on PCV2.

PCV2 has been identified as a causal agent of a lethal wasting disease in pigs.

Panelist Dr. Harry Greenberg, the Joseph D. Grant Professor of Medicine and Microbiology and Immunology, Stanford (Calif.) University, said that the vaccine risks “would have to be immense” to outweigh the benefits. But he added that more studies are needed to determine that PCV does not cause human infections and recommended more studies of vaccinees, including serial testing of stool specimens for evidence of viral replication. (He disclosed that he was involved in the development of the first rotavirus vaccine and is a strong proponent of rotavirus vaccination, but has no personal financial relationship to the manufacturers.)

The panel's consumer representative, Vicky Debold, director of patient safety at the National Vaccine Information Center, Vienna, Va., said that the available evidence was “colored by a great deal of uncertainty.”

More information for clinicians is available at www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205548.htm

The use of Rotarix can be resumed and the use of RotaTeq continued because there is no evidence that the porcine virus detected in both rotavirus vaccines poses a safety risk to humans, according to the Food and Drug Administration.

The FDA based its decision on laboratory results from the manufacturers of the two rotavirus vaccines and from FDA laboratories, on a scientific literature review, and on input from scientific and public health experts, according to a statement issued by the agency on May 14. In addition, the agency does not believe a medical follow-up is needed for children who have been vaccinated with these vaccines.

Those experts include the FDA's Vaccines and Related Biological Products Advisory Committee, which met a week before the agency announcement to discuss the recent identification of porcine circovirus (PCV) type 1 DNA in GlaxoSmithKline's rotavirus vaccine, Rotarix, which resulted in the FDA's recommendation to temporarily suspend the use of Rotarix on March 22. At the recent meeting, the FDA announced that PCV has also been detected in Merck & Co.'s rotavirus vaccine, RotaTeq.

In addition, the panel agreed that the benefits of the two rotavirus vaccines greatly outweighed the theoretical risk that the detection of PCV in the vaccines could cause human infection, but recommended more study of this potential risk.

Panelists generally agreed that they were encouraged by the available data that did not indicate that PCV detected in the vaccines caused human infection, but noted that this had not yet been proved. Among the panel's recommendations for further studies were serology studies of children with cystic fibrosis on long-term pancreatic enzyme supplementation to check for evidence of antibodies to PCV. (Pancreatic enzyme supplements are derived from the pancreas of pigs, where PCV is detected.)

When the temporary suspension of Rotarix use was announced in March, the FDA said that PCV1 DNA had not been found in RotaTeq, but recommended that Merck conduct tests. At the meeting, Dr. Norman Baylor, the director of the FDA's Office of Vaccines Research and Review, told the panel that at the May meeting, Merck had informed the agency that fragments of DNA from PCV type 1 and type 2 have been identified in the vaccine in preliminary studies. But no recommendation to suspend the use of this vaccine was made at that time.

PCV is common among pigs but is not known to cause disease in humans. There is currently no evidence that PCV in rotavirus vaccines licensed in the United States pose a human safety risk, according to Dr. Baylor. In a statement issued late on May 6, Merck said that the levels of PCV DNA detected in RotaTeq were “very low,” and that “there is no evidence at this time that DNA from PCV causes any disease in humans.”

At the meeting, GSK presented results of studies conducted since PCV DNA was detected in Rotarix, which has not provided any evidence that PCV1 in Rotarix causes infections in humans, according to the presenters. The company tested stool and blood samples taken from vaccine recipients in four Rotarix clinical trials conducted in Africa, Asia, Latin America, and Europe, which included three studies of healthy infants and one of HIV-positive infants. Overall, PCV1 DNA was detected in the stool of four infants, on the third day after vaccination, which the company said was suggestive of “transient passage” of the PCV DNA through the GI tract, but none of these infants or any other infants in the trials had evidence of antibodies to PCV1 in blood samples that had been taken after they received the last vaccine dose, according to GSK.

The FDA and the companies are continuing to conduct studies.

“We have data to suggest this virus is probably not pathogenic in humans,” said panelist Dr. Jos Romero, chief, pediatric infectious diseases, Arkansas Children's Hospital, Little Rock. “Whether it can infect humans still remains a question, but it looks like it doesn't cause disease,” added Dr. Romero, who, like other panelists, said that more studies are definitely needed. He and others agreed that this should include more research on PCV2.

PCV2 has been identified as a causal agent of a lethal wasting disease in pigs.

Panelist Dr. Harry Greenberg, the Joseph D. Grant Professor of Medicine and Microbiology and Immunology, Stanford (Calif.) University, said that the vaccine risks “would have to be immense” to outweigh the benefits. But he added that more studies are needed to determine that PCV does not cause human infections and recommended more studies of vaccinees, including serial testing of stool specimens for evidence of viral replication. (He disclosed that he was involved in the development of the first rotavirus vaccine and is a strong proponent of rotavirus vaccination, but has no personal financial relationship to the manufacturers.)

The panel's consumer representative, Vicky Debold, director of patient safety at the National Vaccine Information Center, Vienna, Va., said that the available evidence was “colored by a great deal of uncertainty.”

More information for clinicians is available at www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205548.htm

The use of Rotarix can be resumed and the use of RotaTeq continued because there is no evidence that the porcine virus detected in both rotavirus vaccines poses a safety risk to humans, according to the Food and Drug Administration.

The FDA based its decision on laboratory results from the manufacturers of the two rotavirus vaccines and from FDA laboratories, on a scientific literature review, and on input from scientific and public health experts, according to a statement issued by the agency on May 14. In addition, the agency does not believe a medical follow-up is needed for children who have been vaccinated with these vaccines.

Those experts include the FDA's Vaccines and Related Biological Products Advisory Committee, which met a week before the agency announcement to discuss the recent identification of porcine circovirus (PCV) type 1 DNA in GlaxoSmithKline's rotavirus vaccine, Rotarix, which resulted in the FDA's recommendation to temporarily suspend the use of Rotarix on March 22. At the recent meeting, the FDA announced that PCV has also been detected in Merck & Co.'s rotavirus vaccine, RotaTeq.

In addition, the panel agreed that the benefits of the two rotavirus vaccines greatly outweighed the theoretical risk that the detection of PCV in the vaccines could cause human infection, but recommended more study of this potential risk.

Panelists generally agreed that they were encouraged by the available data that did not indicate that PCV detected in the vaccines caused human infection, but noted that this had not yet been proved. Among the panel's recommendations for further studies were serology studies of children with cystic fibrosis on long-term pancreatic enzyme supplementation to check for evidence of antibodies to PCV. (Pancreatic enzyme supplements are derived from the pancreas of pigs, where PCV is detected.)

When the temporary suspension of Rotarix use was announced in March, the FDA said that PCV1 DNA had not been found in RotaTeq, but recommended that Merck conduct tests. At the meeting, Dr. Norman Baylor, the director of the FDA's Office of Vaccines Research and Review, told the panel that at the May meeting, Merck had informed the agency that fragments of DNA from PCV type 1 and type 2 have been identified in the vaccine in preliminary studies. But no recommendation to suspend the use of this vaccine was made at that time.

PCV is common among pigs but is not known to cause disease in humans. There is currently no evidence that PCV in rotavirus vaccines licensed in the United States pose a human safety risk, according to Dr. Baylor. In a statement issued late on May 6, Merck said that the levels of PCV DNA detected in RotaTeq were “very low,” and that “there is no evidence at this time that DNA from PCV causes any disease in humans.”

At the meeting, GSK presented results of studies conducted since PCV DNA was detected in Rotarix, which has not provided any evidence that PCV1 in Rotarix causes infections in humans, according to the presenters. The company tested stool and blood samples taken from vaccine recipients in four Rotarix clinical trials conducted in Africa, Asia, Latin America, and Europe, which included three studies of healthy infants and one of HIV-positive infants. Overall, PCV1 DNA was detected in the stool of four infants, on the third day after vaccination, which the company said was suggestive of “transient passage” of the PCV DNA through the GI tract, but none of these infants or any other infants in the trials had evidence of antibodies to PCV1 in blood samples that had been taken after they received the last vaccine dose, according to GSK.

The FDA and the companies are continuing to conduct studies.

“We have data to suggest this virus is probably not pathogenic in humans,” said panelist Dr. Jos Romero, chief, pediatric infectious diseases, Arkansas Children's Hospital, Little Rock. “Whether it can infect humans still remains a question, but it looks like it doesn't cause disease,” added Dr. Romero, who, like other panelists, said that more studies are definitely needed. He and others agreed that this should include more research on PCV2.

PCV2 has been identified as a causal agent of a lethal wasting disease in pigs.

Panelist Dr. Harry Greenberg, the Joseph D. Grant Professor of Medicine and Microbiology and Immunology, Stanford (Calif.) University, said that the vaccine risks “would have to be immense” to outweigh the benefits. But he added that more studies are needed to determine that PCV does not cause human infections and recommended more studies of vaccinees, including serial testing of stool specimens for evidence of viral replication. (He disclosed that he was involved in the development of the first rotavirus vaccine and is a strong proponent of rotavirus vaccination, but has no personal financial relationship to the manufacturers.)

The panel's consumer representative, Vicky Debold, director of patient safety at the National Vaccine Information Center, Vienna, Va., said that the available evidence was “colored by a great deal of uncertainty.”

More information for clinicians is available at www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205548.htm

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR. 2010;14:413-7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.) The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in 2009 and in the future. “The increase in the CS rate, the substantial burden of [primary and secondary] syphilis among black women in the South, and the high case-fatality ratio associated with CS require that CS prevention be given high priority in areas with high syphilis morbidity and evidence of heterosexual syphilis transmission.”

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR. 2010;14:413-7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.) The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in 2009 and in the future. “The increase in the CS rate, the substantial burden of [primary and secondary] syphilis among black women in the South, and the high case-fatality ratio associated with CS require that CS prevention be given high priority in areas with high syphilis morbidity and evidence of heterosexual syphilis transmission.”

The congenital syphilis rate in the United States increased between 2005 and 2008, after dropping over the previous 14 years, which reflects an increase in the rate of primary and secondary syphilis cases among women, based on a report from the Centers for Disease Control and Prevention.

In 2008, there were 431 cases of congenital syphilis (CS) reported to state and local health departments in the United States, according to the report on the trends in CS cases in the United States, based on national surveillance data between 2003 and 2008 (MMWR. 2010;14:413-7).

However, this was an increase from 339 cases reported in 2005. And the CS rate increased by 23% during this time, from 8.2 cases per 100,000 live births in 2005 to 10.1 cases per 100,000 live births in 2008. Most of this increase was attributed to trends in the South, where the rate increased from 9.6 to 15.7/100,000 live births between 2005 and 2008—a 64% increase. In the Northeast, the rate increased from 4.2 to 5.4/100,000 live births—a 29% increase.

Before this time, the CS rates had dropped, from 10.6 cases per 100,000 live births in 2003, to 8.2 cases per 100,000 live births in 2005 (which continued the decline from 1995, when the rate was almost 50 cases per 100,000 live births). The number of CS cases dropped from 432 in 2003 to 339 in 2005.

The increase in CS cases between 2005 and 2008 was preceded by a 38% increase in the rate of primary and secondary (P&S) syphilis among females aged 10 and older from 2004 to 2007, which continued to increase in 2008, according to the report, which noted that this trend may have been associated with the use of crack cocaine and commercial sex work.

Between 2005 and 2008, most of the increase in CS was seen among infants born to black mothers. In this group, the CS rate increased from 26.6 to 34.6 per 100,000 live births between 2005 and 2008—a 30% increase. (There were 156 cases in 2005 and 215 cases in 2008.) The percentage of infants with CS born to black mothers who lived in the South increased from 51% in 2005 to 75% in 2008.

Between 2005 and 2008, there was a 2% increase in the CS rate among infants born to Hispanic mothers (12.6 to 12.8 cases per 100,000 live births) and a 115% increase among infants born to white mothers (1.3 to 2.8 cases per 100,000 live births). But the report pointed out that the number of infants with CS born to white mothers was small: 31 cases in 2005 and 65 in 2008.

In 2008, infants of black mothers accounted for 50% of CS cases; infants of Hispanic mothers, 31%; infants of white mothers, 15%; and infants of Asian/Pacific Islander and American Indian/Alaskan Native mothers, 2% and 1%. The remaining 1% of infants had mothers of unknown race/ethnicity.

The CDC recommends that all pregnant women be tested for syphilis at the first prenatal visit, but the mothers of 125 (nearly 30%) of the 431 infants with CS reported in 2008 had not received prenatal care, and syphilis was detected at delivery. Of the 276 infants (64%) whose mothers had received prenatal care, the mothers of 75 infants (27%) were first screened for syphilis within 30 days of delivery; 67 (24%) mothers had a positive screen more than 30 days before delivery but had not been treated. For the remaining 30 infants, whether the mother had received prenatal care was not known.

Of the cases reported in 2008, 25 (6%) were stillborn and 3 (1%) died within 30 days of delivery, for a case fatality ratio of 6.5%.

An editorial comment on the findings pointed out that the increase in the primary and secondary syphilis rate from 1.1/1,000 females in 2007 to 1.5/1,000 females in 2008 “might portend a larger increase” in 2009 and in the future. “The increase in the CS rate, the substantial burden of [primary and secondary] syphilis among black women in the South, and the high case-fatality ratio associated with CS require that CS prevention be given high priority in areas with high syphilis morbidity and evidence of heterosexual syphilis transmission.”

An Institute of Medicine report recommends changing federal standards to require a marked reduction in the amount of sodium that can be added to food by manufacturers, restaurants, and food service companies.

The report on strategies to reduce sodium intake recommends an incremental stepwise approach that would gradually reduce sodium content to allow people to become accustomed to lower sodium levels in food.

Excessive dietary sodium intake in the United States is an “urgent public health problem,” Dr. Jane E. Henney, chair of the committee that wrote the report, said during a briefing held by the IOM.

The report's main recommendation calls for the Food and Drug Administration to set mandatory standards for the safe levels of sodium that is added to food. Reducing sodium intake has the potential to prevent 100,000 deaths per year and save billions in health care costs, she said. The average amount consumed in the United States is “far beyond” the essential levels needed, noted Dr. Henney, professor of medicine at the University of Cincinnati—an average of more than 3,400 mg of sodium a day, or about 50% more than the recommended maximum recommended intake of 2,300 mg.

A statement issued by the FDA in response to the release of the IOM report said that the agency plans to review the report's recommendations and will “continue to work with other federal agencies, public health and consumer groups, and the food industry to support the reduction of sodium levels in the food supply.” In addition, an interagency working group on sodium will be established by of the Department of Health and Human Services.

The IOM report, done at the request of Congress in 2008, was sponsored by the FDA; the Centers for Disease Control and Prevention; the National Heart, Lung, and Blood Institute; and the Office of Disease Prevention and Health Promotion at HHS.

The report is available at www.iom.edu/Reports/2010/Strategies-to-Reduce-Sodium-Intake-in-the-United-States.aspx

An Institute of Medicine report recommends changing federal standards to require a marked reduction in the amount of sodium that can be added to food by manufacturers, restaurants, and food service companies.

The report on strategies to reduce sodium intake recommends an incremental stepwise approach that would gradually reduce sodium content to allow people to become accustomed to lower sodium levels in food.

Excessive dietary sodium intake in the United States is an “urgent public health problem,” Dr. Jane E. Henney, chair of the committee that wrote the report, said during a briefing held by the IOM.

The report's main recommendation calls for the Food and Drug Administration to set mandatory standards for the safe levels of sodium that is added to food. Reducing sodium intake has the potential to prevent 100,000 deaths per year and save billions in health care costs, she said. The average amount consumed in the United States is “far beyond” the essential levels needed, noted Dr. Henney, professor of medicine at the University of Cincinnati—an average of more than 3,400 mg of sodium a day, or about 50% more than the recommended maximum recommended intake of 2,300 mg.

A statement issued by the FDA in response to the release of the IOM report said that the agency plans to review the report's recommendations and will “continue to work with other federal agencies, public health and consumer groups, and the food industry to support the reduction of sodium levels in the food supply.” In addition, an interagency working group on sodium will be established by of the Department of Health and Human Services.

The IOM report, done at the request of Congress in 2008, was sponsored by the FDA; the Centers for Disease Control and Prevention; the National Heart, Lung, and Blood Institute; and the Office of Disease Prevention and Health Promotion at HHS.

The report is available at www.iom.edu/Reports/2010/Strategies-to-Reduce-Sodium-Intake-in-the-United-States.aspx

An Institute of Medicine report recommends changing federal standards to require a marked reduction in the amount of sodium that can be added to food by manufacturers, restaurants, and food service companies.

The report on strategies to reduce sodium intake recommends an incremental stepwise approach that would gradually reduce sodium content to allow people to become accustomed to lower sodium levels in food.

Excessive dietary sodium intake in the United States is an “urgent public health problem,” Dr. Jane E. Henney, chair of the committee that wrote the report, said during a briefing held by the IOM.

The report's main recommendation calls for the Food and Drug Administration to set mandatory standards for the safe levels of sodium that is added to food. Reducing sodium intake has the potential to prevent 100,000 deaths per year and save billions in health care costs, she said. The average amount consumed in the United States is “far beyond” the essential levels needed, noted Dr. Henney, professor of medicine at the University of Cincinnati—an average of more than 3,400 mg of sodium a day, or about 50% more than the recommended maximum recommended intake of 2,300 mg.

A statement issued by the FDA in response to the release of the IOM report said that the agency plans to review the report's recommendations and will “continue to work with other federal agencies, public health and consumer groups, and the food industry to support the reduction of sodium levels in the food supply.” In addition, an interagency working group on sodium will be established by of the Department of Health and Human Services.

The IOM report, done at the request of Congress in 2008, was sponsored by the FDA; the Centers for Disease Control and Prevention; the National Heart, Lung, and Blood Institute; and the Office of Disease Prevention and Health Promotion at HHS.

The report is available at www.iom.edu/Reports/2010/Strategies-to-Reduce-Sodium-Intake-in-the-United-States.aspx

The Food and Drug Administration has approved the oral antibiotic rifaximin as a treatment to reduce the risk of developing episodes of overt hepatic encephalopathy in adults with chronic liver disease, making this the second drug approved for this indication.

Approved in 2004 for treating travelers' diarrhea caused by noninvasive strains of Escherichia coli in people aged 12 and older, rifaximin is a poorly absorbed oral antibiotic derived from rifamycin, and has a broad spectrum of activity against gram-positive and gram-negative, aerobic and anaerobic enteric bacteria.

Rifaximin reduces levels of gut-derived neurotoxins such as ammonia, which is known to cause hepatic encephalopathy in patients with hepatic impairment, according to the manufacturer, Salix Pharmaceuticals, which markets the drug as Xifaxan.

The approval is for “reduction in risk of overt hepatic encephalopathy recurrence” in patients aged 18 and older. The approved dosage is one 550-mg tablet taken orally twice a day, with or without food.

Approva l was based on a study comparing treatment with rifaximin to placebo in 299 patients with advanced liver disease. The study was published on March 25, the same day that the FDA announced the approval (N. Engl. J. Med. 2010;362:1071-81).

During the 6-month study, 31 of 140 patients (22%) on rifaximin and 73 of 159 (46%) on placebo had a breakthrough episode, a significant difference that represented a nearly 60% reduction in risk. Secondary end points, including the risk of hepatic encephalopathy–related hospitalizations, also were significantly reduced among those on rifaximin.

Based on the findings, the FDA's Gastrointestinal Drugs Advisory Committee voted 14-4 in February that the risk-benefit profile of rifaximin supported its approval for this indication. The panelists supporting approval emphasized that the drug's labeling should clearly inform prescribers that most of the patients (91%) who participated in the study submitted for approval were also being treated with lactulose, a drug approved in the 1970s for the indication, and that most had Child-Pugh class A or B cirrhosis.

The safety of rifaximin was uncertain when used for more severe liver disease, as was its efficacy as a single agent.

During their meeting in Silver Spring, Md., panelists said that if the drug was approved, these questions would need to be addressed in postmarketing studies, which should evaluate the safety of the drug in patients with more severe disease, those with Child-Pugh class C cirrhosis or a model for end-stage liver disease (MELD) score above 25.

The safety of chronic treatment, including the effects of long-term use on the gut flora, also was unclear, and should be studied further if the drug was approved, panelists said. Also, the clinical trial conducted by the manufacturer for this indication was for 6 months, but treatment is expected to continue until the patient undergoes a liver transplant or dies. The longest follow-up that Salix has done is an average of 1 year in patients followed in an extension study.

These concerns were reflected in the revised label, which states in the warning and precautions section that the drug should be used “with caution” in patients with severe (Child-Pugh C) hepatic impairment. The label also says that Clostridium difficile–associated diarrhea should be considered if a patient develops diarrhea during treatment and it does not improve or gets worse.

In the randomized, controlled study of 299 patients with advanced liver disease, treatment with rifaximin at a dose of 550 mg twice a day was compared with placebo. In the study, conducted by Dr. Nathan M. Bass of the University of California, San Francisco, and his associates, most of the patients were white, and the average age was 56 years. Patients were treated at 70 medical centers in the United States, Russia, and Canada starting in 2005.

Participants had Conn scores of 0 (two-thirds of the patients) or 1. They had had at least two episodes of hepatic encephalopathy, defined as a Conn score of at least 2, in the previous 6 months.

The 5-point Conn grading system is based on a clinician's subjective assessment, a concern raised by FDA reviewers. A score of 0 indicates that no abnormality was detected, whereas a score of 1 indicates trivial lack of awareness, shortened attention span, impaired addition or subtraction, euphoria, or anxiety. A score of 2 is used to indicate lethargy or apathy, disorientation to time, obvious personality change, and/or inappropriate behavior, and a score of 4 indicates coma (unable to test mental state).

Neurologic impairment was also evaluated with the Asterixis score, which ranges from grade 0 (no tremors) and grade 1 (rare flapping motions) to grade 2 (occasional, irregular flaps), grade 3 (frequent flaps), and grade 4 (almost continuous flapping motions).

The primary end point was the time to first breakthrough overt hepatic encephalopathy episode, defined as an increase of the Conn score to a 2 or higher, or an increase in the Conn score and Asterixis grade of 1 each among those with a baseline Conn score of 0.

The active drug also reduced the relative risk for hospitalization by 50%. Hospitalization involving hepatic encephalopathy was reported for 13.6% of patients on rifaximin and 22.6% of those on placebo.

Mortality was 6% (9 of 140) with rifaximin and 7% (11 of 159) with placebo; deaths were due mostly to worsening hepatic function and progression of the underlying disease.

Since the drug was approved more than 5 years ago for traveler's diarrhea, there have been five postmarketing reports of C. difficile colitis associated with rifaximin treatment, including one death, according to the FDA.

In addition, anaphylaxis has been identified as a notable adverse effect in postmarketing reports, and this risk is now included in the drug's label.

“These data suggest that four patients would need to be treated with rifaximin for 6 months to prevent one episode of overt hepatic encephalopathy,” Dr. Bass and his colleagues said. First approved in Italy in 1985, rifaximin is now approved in 33 countries for various GI uses, including hepatic encephalopathy and adjunctive treatment of hyperammonemia, according to the manufacturer.

Disclosures: The study was supported by Salix Pharmaceuticals. Dr. Bass reported receiving consulting, advisory, and lecture fees from Salix. Members of FDA advisory panels have been cleared for potential conflicts of interest related to the topic under review prior to the meeting.

My Take

Try Lactulose, Then Rifaximin

Hepatic encephalopathy, a frequent complication for patients with cirrhosis, results in disability that is generally recognized as episodes of overt confusion. Minimal hepatic encephalopathy from cirrhosis may be more difficult to recognize, because it produces less-overt complications such as impaired driving and automobile accidents.

Lactulose, a nonabsorbable disaccharide that alters colonic pH and bowel frequency, has been the mainstay of therapy for hepatic encephalopathy, although the laxative effect of lactulose can be a problem for some patients. Rifaximin, an antibiotic with limited absorption, reduces the frequency of episodes of hepatic encephalopathy in patients with cirrhosis and thus offers another therapeutic option.

Given the associated cost savings, I typically use lactulose as first-line therapy for most patients with hepatic encephalopathy, and reserve rifaximin for those who are poorly controlled or who develop significant GI side effects from lactulose.

ROWEN K. ZETTERMAN, M.D., a gastroenterologist, is dean of the school of medicine at Creighton University, Omaha, Neb. He reported no relevant conflicts of interest.

Vitals

The Food and Drug Administration has approved the oral antibiotic rifaximin as a treatment to reduce the risk of developing episodes of overt hepatic encephalopathy in adults with chronic liver disease, making this the second drug approved for this indication.

Approved in 2004 for treating travelers' diarrhea caused by noninvasive strains of Escherichia coli in people aged 12 and older, rifaximin is a poorly absorbed oral antibiotic derived from rifamycin, and has a broad spectrum of activity against gram-positive and gram-negative, aerobic and anaerobic enteric bacteria.

Rifaximin reduces levels of gut-derived neurotoxins such as ammonia, which is known to cause hepatic encephalopathy in patients with hepatic impairment, according to the manufacturer, Salix Pharmaceuticals, which markets the drug as Xifaxan.

The approval is for “reduction in risk of overt hepatic encephalopathy recurrence” in patients aged 18 and older. The approved dosage is one 550-mg tablet taken orally twice a day, with or without food.

Approva l was based on a study comparing treatment with rifaximin to placebo in 299 patients with advanced liver disease. The study was published on March 25, the same day that the FDA announced the approval (N. Engl. J. Med. 2010;362:1071-81).

During the 6-month study, 31 of 140 patients (22%) on rifaximin and 73 of 159 (46%) on placebo had a breakthrough episode, a significant difference that represented a nearly 60% reduction in risk. Secondary end points, including the risk of hepatic encephalopathy–related hospitalizations, also were significantly reduced among those on rifaximin.

Based on the findings, the FDA's Gastrointestinal Drugs Advisory Committee voted 14-4 in February that the risk-benefit profile of rifaximin supported its approval for this indication. The panelists supporting approval emphasized that the drug's labeling should clearly inform prescribers that most of the patients (91%) who participated in the study submitted for approval were also being treated with lactulose, a drug approved in the 1970s for the indication, and that most had Child-Pugh class A or B cirrhosis.

The safety of rifaximin was uncertain when used for more severe liver disease, as was its efficacy as a single agent.

During their meeting in Silver Spring, Md., panelists said that if the drug was approved, these questions would need to be addressed in postmarketing studies, which should evaluate the safety of the drug in patients with more severe disease, those with Child-Pugh class C cirrhosis or a model for end-stage liver disease (MELD) score above 25.

The safety of chronic treatment, including the effects of long-term use on the gut flora, also was unclear, and should be studied further if the drug was approved, panelists said. Also, the clinical trial conducted by the manufacturer for this indication was for 6 months, but treatment is expected to continue until the patient undergoes a liver transplant or dies. The longest follow-up that Salix has done is an average of 1 year in patients followed in an extension study.

These concerns were reflected in the revised label, which states in the warning and precautions section that the drug should be used “with caution” in patients with severe (Child-Pugh C) hepatic impairment. The label also says that Clostridium difficile–associated diarrhea should be considered if a patient develops diarrhea during treatment and it does not improve or gets worse.

In the randomized, controlled study of 299 patients with advanced liver disease, treatment with rifaximin at a dose of 550 mg twice a day was compared with placebo. In the study, conducted by Dr. Nathan M. Bass of the University of California, San Francisco, and his associates, most of the patients were white, and the average age was 56 years. Patients were treated at 70 medical centers in the United States, Russia, and Canada starting in 2005.

Participants had Conn scores of 0 (two-thirds of the patients) or 1. They had had at least two episodes of hepatic encephalopathy, defined as a Conn score of at least 2, in the previous 6 months.

The 5-point Conn grading system is based on a clinician's subjective assessment, a concern raised by FDA reviewers. A score of 0 indicates that no abnormality was detected, whereas a score of 1 indicates trivial lack of awareness, shortened attention span, impaired addition or subtraction, euphoria, or anxiety. A score of 2 is used to indicate lethargy or apathy, disorientation to time, obvious personality change, and/or inappropriate behavior, and a score of 4 indicates coma (unable to test mental state).

Neurologic impairment was also evaluated with the Asterixis score, which ranges from grade 0 (no tremors) and grade 1 (rare flapping motions) to grade 2 (occasional, irregular flaps), grade 3 (frequent flaps), and grade 4 (almost continuous flapping motions).

The primary end point was the time to first breakthrough overt hepatic encephalopathy episode, defined as an increase of the Conn score to a 2 or higher, or an increase in the Conn score and Asterixis grade of 1 each among those with a baseline Conn score of 0.

The active drug also reduced the relative risk for hospitalization by 50%. Hospitalization involving hepatic encephalopathy was reported for 13.6% of patients on rifaximin and 22.6% of those on placebo.

Mortality was 6% (9 of 140) with rifaximin and 7% (11 of 159) with placebo; deaths were due mostly to worsening hepatic function and progression of the underlying disease.

Since the drug was approved more than 5 years ago for traveler's diarrhea, there have been five postmarketing reports of C. difficile colitis associated with rifaximin treatment, including one death, according to the FDA.

In addition, anaphylaxis has been identified as a notable adverse effect in postmarketing reports, and this risk is now included in the drug's label.

“These data suggest that four patients would need to be treated with rifaximin for 6 months to prevent one episode of overt hepatic encephalopathy,” Dr. Bass and his colleagues said. First approved in Italy in 1985, rifaximin is now approved in 33 countries for various GI uses, including hepatic encephalopathy and adjunctive treatment of hyperammonemia, according to the manufacturer.

Disclosures: The study was supported by Salix Pharmaceuticals. Dr. Bass reported receiving consulting, advisory, and lecture fees from Salix. Members of FDA advisory panels have been cleared for potential conflicts of interest related to the topic under review prior to the meeting.

My Take

Try Lactulose, Then Rifaximin

Hepatic encephalopathy, a frequent complication for patients with cirrhosis, results in disability that is generally recognized as episodes of overt confusion. Minimal hepatic encephalopathy from cirrhosis may be more difficult to recognize, because it produces less-overt complications such as impaired driving and automobile accidents.

Lactulose, a nonabsorbable disaccharide that alters colonic pH and bowel frequency, has been the mainstay of therapy for hepatic encephalopathy, although the laxative effect of lactulose can be a problem for some patients. Rifaximin, an antibiotic with limited absorption, reduces the frequency of episodes of hepatic encephalopathy in patients with cirrhosis and thus offers another therapeutic option.

Given the associated cost savings, I typically use lactulose as first-line therapy for most patients with hepatic encephalopathy, and reserve rifaximin for those who are poorly controlled or who develop significant GI side effects from lactulose.

ROWEN K. ZETTERMAN, M.D., a gastroenterologist, is dean of the school of medicine at Creighton University, Omaha, Neb. He reported no relevant conflicts of interest.

Vitals

The Food and Drug Administration has approved the oral antibiotic rifaximin as a treatment to reduce the risk of developing episodes of overt hepatic encephalopathy in adults with chronic liver disease, making this the second drug approved for this indication.

Approved in 2004 for treating travelers' diarrhea caused by noninvasive strains of Escherichia coli in people aged 12 and older, rifaximin is a poorly absorbed oral antibiotic derived from rifamycin, and has a broad spectrum of activity against gram-positive and gram-negative, aerobic and anaerobic enteric bacteria.

Rifaximin reduces levels of gut-derived neurotoxins such as ammonia, which is known to cause hepatic encephalopathy in patients with hepatic impairment, according to the manufacturer, Salix Pharmaceuticals, which markets the drug as Xifaxan.

The approval is for “reduction in risk of overt hepatic encephalopathy recurrence” in patients aged 18 and older. The approved dosage is one 550-mg tablet taken orally twice a day, with or without food.

Approva l was based on a study comparing treatment with rifaximin to placebo in 299 patients with advanced liver disease. The study was published on March 25, the same day that the FDA announced the approval (N. Engl. J. Med. 2010;362:1071-81).

During the 6-month study, 31 of 140 patients (22%) on rifaximin and 73 of 159 (46%) on placebo had a breakthrough episode, a significant difference that represented a nearly 60% reduction in risk. Secondary end points, including the risk of hepatic encephalopathy–related hospitalizations, also were significantly reduced among those on rifaximin.

Based on the findings, the FDA's Gastrointestinal Drugs Advisory Committee voted 14-4 in February that the risk-benefit profile of rifaximin supported its approval for this indication. The panelists supporting approval emphasized that the drug's labeling should clearly inform prescribers that most of the patients (91%) who participated in the study submitted for approval were also being treated with lactulose, a drug approved in the 1970s for the indication, and that most had Child-Pugh class A or B cirrhosis.

The safety of rifaximin was uncertain when used for more severe liver disease, as was its efficacy as a single agent.

During their meeting in Silver Spring, Md., panelists said that if the drug was approved, these questions would need to be addressed in postmarketing studies, which should evaluate the safety of the drug in patients with more severe disease, those with Child-Pugh class C cirrhosis or a model for end-stage liver disease (MELD) score above 25.

The safety of chronic treatment, including the effects of long-term use on the gut flora, also was unclear, and should be studied further if the drug was approved, panelists said. Also, the clinical trial conducted by the manufacturer for this indication was for 6 months, but treatment is expected to continue until the patient undergoes a liver transplant or dies. The longest follow-up that Salix has done is an average of 1 year in patients followed in an extension study.

These concerns were reflected in the revised label, which states in the warning and precautions section that the drug should be used “with caution” in patients with severe (Child-Pugh C) hepatic impairment. The label also says that Clostridium difficile–associated diarrhea should be considered if a patient develops diarrhea during treatment and it does not improve or gets worse.

In the randomized, controlled study of 299 patients with advanced liver disease, treatment with rifaximin at a dose of 550 mg twice a day was compared with placebo. In the study, conducted by Dr. Nathan M. Bass of the University of California, San Francisco, and his associates, most of the patients were white, and the average age was 56 years. Patients were treated at 70 medical centers in the United States, Russia, and Canada starting in 2005.

Participants had Conn scores of 0 (two-thirds of the patients) or 1. They had had at least two episodes of hepatic encephalopathy, defined as a Conn score of at least 2, in the previous 6 months.

The 5-point Conn grading system is based on a clinician's subjective assessment, a concern raised by FDA reviewers. A score of 0 indicates that no abnormality was detected, whereas a score of 1 indicates trivial lack of awareness, shortened attention span, impaired addition or subtraction, euphoria, or anxiety. A score of 2 is used to indicate lethargy or apathy, disorientation to time, obvious personality change, and/or inappropriate behavior, and a score of 4 indicates coma (unable to test mental state).

Neurologic impairment was also evaluated with the Asterixis score, which ranges from grade 0 (no tremors) and grade 1 (rare flapping motions) to grade 2 (occasional, irregular flaps), grade 3 (frequent flaps), and grade 4 (almost continuous flapping motions).

The primary end point was the time to first breakthrough overt hepatic encephalopathy episode, defined as an increase of the Conn score to a 2 or higher, or an increase in the Conn score and Asterixis grade of 1 each among those with a baseline Conn score of 0.

The active drug also reduced the relative risk for hospitalization by 50%. Hospitalization involving hepatic encephalopathy was reported for 13.6% of patients on rifaximin and 22.6% of those on placebo.

Mortality was 6% (9 of 140) with rifaximin and 7% (11 of 159) with placebo; deaths were due mostly to worsening hepatic function and progression of the underlying disease.

Since the drug was approved more than 5 years ago for traveler's diarrhea, there have been five postmarketing reports of C. difficile colitis associated with rifaximin treatment, including one death, according to the FDA.

In addition, anaphylaxis has been identified as a notable adverse effect in postmarketing reports, and this risk is now included in the drug's label.

“These data suggest that four patients would need to be treated with rifaximin for 6 months to prevent one episode of overt hepatic encephalopathy,” Dr. Bass and his colleagues said. First approved in Italy in 1985, rifaximin is now approved in 33 countries for various GI uses, including hepatic encephalopathy and adjunctive treatment of hyperammonemia, according to the manufacturer.

Disclosures: The study was supported by Salix Pharmaceuticals. Dr. Bass reported receiving consulting, advisory, and lecture fees from Salix. Members of FDA advisory panels have been cleared for potential conflicts of interest related to the topic under review prior to the meeting.

My Take

Try Lactulose, Then Rifaximin

Hepatic encephalopathy, a frequent complication for patients with cirrhosis, results in disability that is generally recognized as episodes of overt confusion. Minimal hepatic encephalopathy from cirrhosis may be more difficult to recognize, because it produces less-overt complications such as impaired driving and automobile accidents.

Lactulose, a nonabsorbable disaccharide that alters colonic pH and bowel frequency, has been the mainstay of therapy for hepatic encephalopathy, although the laxative effect of lactulose can be a problem for some patients. Rifaximin, an antibiotic with limited absorption, reduces the frequency of episodes of hepatic encephalopathy in patients with cirrhosis and thus offers another therapeutic option.

Given the associated cost savings, I typically use lactulose as first-line therapy for most patients with hepatic encephalopathy, and reserve rifaximin for those who are poorly controlled or who develop significant GI side effects from lactulose.

ROWEN K. ZETTERMAN, M.D., a gastroenterologist, is dean of the school of medicine at Creighton University, Omaha, Neb. He reported no relevant conflicts of interest.

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