Elizabeth Mechcatie

A fibrin sealant recently approved by the Food and Drug Administration for adhering autologous skin grafts in pediatric and adult burn patients provides an alternative to staples and sutures, according to the agency.

The sealant, derived from pooled human plasma, will be available in July and will be marketed under the trade name Artiss by Baxter Healthcare Corp.

Approval was based on a multicenter study of 138 patients whose mean age was 31 years (15% of the patients were aged 7–18 years). Each patient had one split-thickness skin graft attached with surgical staples and another attached with Artiss.

Artiss was determined to be as good as staples in attaining complete wound closure, according to the FDA: At 28 days, 45% of the Artiss-treated wounds and 37% of the stapled wounds had completely closed.

Adverse reactions with Artiss were skin graft failure (5 of the 138 patients) and pruritus (2 of the 138 patients).

Artiss is almost identical to Tisseel, another fibrin sealant manufactured by Baxter, but contains a much lower concentration of thrombin (4 IU/mL vs. 500 IU/mL in Tisseel), so it provides surgeons “more time to position skin grafts over burns before the graft begins to adhere to the skin,” according to the FDA. Artiss contains aprotinin, a fibrinolysis inhibitor. It is applied in a thin layer.

The availability of Artiss “can help surgeons using a fibrin sealant to fine-tune graft placement on burn sites,” Dr. Jesse L. Goodman, director of the FDA's Center for Biologics Evaluation and Research, said in an FDA statement announcing the approval.

The warnings and precautions section of the Artiss label points out that because it is derived from human plasma, it potentially can transmit infectious diseases and, theoretically, the agent that causes Creutzfeldt-Jakob disease. It is for topical use only and is not approved for hemostasis.

At press time, Baxter did not have a price for Artiss.

A fibrin sealant recently approved by the Food and Drug Administration for adhering autologous skin grafts in pediatric and adult burn patients provides an alternative to staples and sutures, according to the agency.

The sealant, derived from pooled human plasma, will be available in July and will be marketed under the trade name Artiss by Baxter Healthcare Corp.

Approval was based on a multicenter study of 138 patients whose mean age was 31 years (15% of the patients were aged 7–18 years). Each patient had one split-thickness skin graft attached with surgical staples and another attached with Artiss.

Artiss was determined to be as good as staples in attaining complete wound closure, according to the FDA: At 28 days, 45% of the Artiss-treated wounds and 37% of the stapled wounds had completely closed.

Adverse reactions with Artiss were skin graft failure (5 of the 138 patients) and pruritus (2 of the 138 patients).

Artiss is almost identical to Tisseel, another fibrin sealant manufactured by Baxter, but contains a much lower concentration of thrombin (4 IU/mL vs. 500 IU/mL in Tisseel), so it provides surgeons “more time to position skin grafts over burns before the graft begins to adhere to the skin,” according to the FDA. Artiss contains aprotinin, a fibrinolysis inhibitor. It is applied in a thin layer.

The availability of Artiss “can help surgeons using a fibrin sealant to fine-tune graft placement on burn sites,” Dr. Jesse L. Goodman, director of the FDA's Center for Biologics Evaluation and Research, said in an FDA statement announcing the approval.

The warnings and precautions section of the Artiss label points out that because it is derived from human plasma, it potentially can transmit infectious diseases and, theoretically, the agent that causes Creutzfeldt-Jakob disease. It is for topical use only and is not approved for hemostasis.

At press time, Baxter did not have a price for Artiss.

A fibrin sealant recently approved by the Food and Drug Administration for adhering autologous skin grafts in pediatric and adult burn patients provides an alternative to staples and sutures, according to the agency.

The sealant, derived from pooled human plasma, will be available in July and will be marketed under the trade name Artiss by Baxter Healthcare Corp.

Approval was based on a multicenter study of 138 patients whose mean age was 31 years (15% of the patients were aged 7–18 years). Each patient had one split-thickness skin graft attached with surgical staples and another attached with Artiss.

Artiss was determined to be as good as staples in attaining complete wound closure, according to the FDA: At 28 days, 45% of the Artiss-treated wounds and 37% of the stapled wounds had completely closed.

Adverse reactions with Artiss were skin graft failure (5 of the 138 patients) and pruritus (2 of the 138 patients).

Artiss is almost identical to Tisseel, another fibrin sealant manufactured by Baxter, but contains a much lower concentration of thrombin (4 IU/mL vs. 500 IU/mL in Tisseel), so it provides surgeons “more time to position skin grafts over burns before the graft begins to adhere to the skin,” according to the FDA. Artiss contains aprotinin, a fibrinolysis inhibitor. It is applied in a thin layer.

The availability of Artiss “can help surgeons using a fibrin sealant to fine-tune graft placement on burn sites,” Dr. Jesse L. Goodman, director of the FDA's Center for Biologics Evaluation and Research, said in an FDA statement announcing the approval.

The warnings and precautions section of the Artiss label points out that because it is derived from human plasma, it potentially can transmit infectious diseases and, theoretically, the agent that causes Creutzfeldt-Jakob disease. It is for topical use only and is not approved for hemostasis.

At press time, Baxter did not have a price for Artiss.

The Food and Drug Administration has approved an implantable ventricular assist device that is markedly smaller than previously available devices and is the first that can be used in smaller adults, which will make this technology available to many more women with heart failure.

The agency announced the approval of the HeartMate II LVAS (Left Ventricular Assist System), a continuous flow left ventricular assist device manufactured by Thoratec Corp., for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure.

The device has a “novel design that is the first to mechanically support the weakened heart of a small-sized adult man or woman with heart failure who is at risk of dying while awaiting a heart transplant,” the FDA said in a statement. It is intended for use inside and outside the hospital and is contraindicated in patients who cannot tolerate anticoagulation therapy.

The HeartMate II is smaller than the other available devices because it uses a continuous flow pump instead of the standard pulsatile pump. It is three inches long and weighs about a pound.

Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement that until this approval, “some heart transplant candidates have been underserved due to the large size of previously approved heart assist devices.” Previously available devices have been too large to implant in many smaller patients.

The HeartMate II, an axial flow, rotary ventricular assist system that can generate flows of up to 10 liters of blood a minute, is attached to the apex of the left ventricle, and “diverts blood from the weakened left ventricle, and propels it to the rest of the body,” according to the product labeling. The device is being studied as destination therapy.

The HeartMate II is about one-seventh the size and about one-fifth the weight of previously available devices, and is noiseless, easier to implant, and easier to wear and tolerate than the previous generation of devices, said Dr. Leslie Miller, chair of cardiology, Washington (D.C.) Hospital Center, who is an investigator and author of studies of the device. Compared with Thoratec's XVE LVAD, which is about the size of a softball, the HeartMate II pump is about the size of a flashlight battery, he noted.

“It's a completely new technology,” Dr. Miller said in an interview, noting that a major advance is that the device increases the availability of the technology to women, because previous devices were too big for many women, which is why about 90% of people in clinical trials of the devices have been men.

The HeartMate II can be implanted in women with a body surface area as small as 1.3 m

At a meeting of the FDA's Circulatory System Devices Panel in November 2007, the panel unanimously recommended approval of the HeartMate II, with conditions that included a postapproval study, with a comparator, and the need to obtain more data in smaller patients (those with a body surface area of less than 1.3 m

Thoratec said it will conduct a postapproval study of the HeartMate II, which will follow 169 recipients and will collect data on survival, adverse events, patient gender, small patients, and anticoagulation levels, and will include a comparator group.

HeartMate II is connected to external equipment via a percutaneous cable. Reprinted with permission from Thoratec Corporation

The Food and Drug Administration has approved an implantable ventricular assist device that is markedly smaller than previously available devices and is the first that can be used in smaller adults, which will make this technology available to many more women with heart failure.

The agency announced the approval of the HeartMate II LVAS (Left Ventricular Assist System), a continuous flow left ventricular assist device manufactured by Thoratec Corp., for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure.

The device has a “novel design that is the first to mechanically support the weakened heart of a small-sized adult man or woman with heart failure who is at risk of dying while awaiting a heart transplant,” the FDA said in a statement. It is intended for use inside and outside the hospital and is contraindicated in patients who cannot tolerate anticoagulation therapy.

The HeartMate II is smaller than the other available devices because it uses a continuous flow pump instead of the standard pulsatile pump. It is three inches long and weighs about a pound.

Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement that until this approval, “some heart transplant candidates have been underserved due to the large size of previously approved heart assist devices.” Previously available devices have been too large to implant in many smaller patients.

The HeartMate II, an axial flow, rotary ventricular assist system that can generate flows of up to 10 liters of blood a minute, is attached to the apex of the left ventricle, and “diverts blood from the weakened left ventricle, and propels it to the rest of the body,” according to the product labeling. The device is being studied as destination therapy.

The HeartMate II is about one-seventh the size and about one-fifth the weight of previously available devices, and is noiseless, easier to implant, and easier to wear and tolerate than the previous generation of devices, said Dr. Leslie Miller, chair of cardiology, Washington (D.C.) Hospital Center, who is an investigator and author of studies of the device. Compared with Thoratec's XVE LVAD, which is about the size of a softball, the HeartMate II pump is about the size of a flashlight battery, he noted.

“It's a completely new technology,” Dr. Miller said in an interview, noting that a major advance is that the device increases the availability of the technology to women, because previous devices were too big for many women, which is why about 90% of people in clinical trials of the devices have been men.

The HeartMate II can be implanted in women with a body surface area as small as 1.3 m

At a meeting of the FDA's Circulatory System Devices Panel in November 2007, the panel unanimously recommended approval of the HeartMate II, with conditions that included a postapproval study, with a comparator, and the need to obtain more data in smaller patients (those with a body surface area of less than 1.3 m

Thoratec said it will conduct a postapproval study of the HeartMate II, which will follow 169 recipients and will collect data on survival, adverse events, patient gender, small patients, and anticoagulation levels, and will include a comparator group.

HeartMate II is connected to external equipment via a percutaneous cable. Reprinted with permission from Thoratec Corporation

The Food and Drug Administration has approved an implantable ventricular assist device that is markedly smaller than previously available devices and is the first that can be used in smaller adults, which will make this technology available to many more women with heart failure.

The agency announced the approval of the HeartMate II LVAS (Left Ventricular Assist System), a continuous flow left ventricular assist device manufactured by Thoratec Corp., for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure.

The device has a “novel design that is the first to mechanically support the weakened heart of a small-sized adult man or woman with heart failure who is at risk of dying while awaiting a heart transplant,” the FDA said in a statement. It is intended for use inside and outside the hospital and is contraindicated in patients who cannot tolerate anticoagulation therapy.

The HeartMate II is smaller than the other available devices because it uses a continuous flow pump instead of the standard pulsatile pump. It is three inches long and weighs about a pound.

Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement that until this approval, “some heart transplant candidates have been underserved due to the large size of previously approved heart assist devices.” Previously available devices have been too large to implant in many smaller patients.

The HeartMate II, an axial flow, rotary ventricular assist system that can generate flows of up to 10 liters of blood a minute, is attached to the apex of the left ventricle, and “diverts blood from the weakened left ventricle, and propels it to the rest of the body,” according to the product labeling. The device is being studied as destination therapy.

The HeartMate II is about one-seventh the size and about one-fifth the weight of previously available devices, and is noiseless, easier to implant, and easier to wear and tolerate than the previous generation of devices, said Dr. Leslie Miller, chair of cardiology, Washington (D.C.) Hospital Center, who is an investigator and author of studies of the device. Compared with Thoratec's XVE LVAD, which is about the size of a softball, the HeartMate II pump is about the size of a flashlight battery, he noted.

“It's a completely new technology,” Dr. Miller said in an interview, noting that a major advance is that the device increases the availability of the technology to women, because previous devices were too big for many women, which is why about 90% of people in clinical trials of the devices have been men.

The HeartMate II can be implanted in women with a body surface area as small as 1.3 m

At a meeting of the FDA's Circulatory System Devices Panel in November 2007, the panel unanimously recommended approval of the HeartMate II, with conditions that included a postapproval study, with a comparator, and the need to obtain more data in smaller patients (those with a body surface area of less than 1.3 m

Thoratec said it will conduct a postapproval study of the HeartMate II, which will follow 169 recipients and will collect data on survival, adverse events, patient gender, small patients, and anticoagulation levels, and will include a comparator group.

HeartMate II is connected to external equipment via a percutaneous cable. Reprinted with permission from Thoratec Corporation

ROCKVILLE, MD. — A Food and Drug Administration advisory panel was split on whether the efficacy and safety data on doripenem, an injectable, broad-spectrum antibiotic, were adequate to support its approval for treating nosocomial pneumonia including ventilator-associated pneumonia.

At a meeting of the FDA's Anti-Infective Drugs Advisory Committee, the panel voted 7 to 6 that the clinical efficacy data from two noninferiority studies comparing doripenem with other antibiotics supported approval of the drug for this indication. The panel voted 8 to 5 that doripenem was safe for treating patients with nosocomial pneumonia including ventilator-assisted pneumonia (VAP) based on the trial data.

Johnson & Johnson Pharmaceutical Research and Development has proposed that doripenem be approved for treating nosocomial pneumonia, including VAP.

Those voting against approval had concerns about the studies, which included irregularities in the data and excess mortality in patients in one of the two studies among doripenem-treated patients. Several of those voting yes said they were supporting approval with reservations, citing the same reasons.

Doripenem, marketed as Doribax, was approved in October 2007 for treating complicated urinary tract infections and complicated intra-abdominal infections. Doripenem is a carbapenem in the β-lactam class of antibacterial agents that has broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria, according to the company.

The data submitted for approval included two phase III, multicenter, randomized, open label, active control studies of adults with clinical, radiologic, and microbiologic evidence of nosocomial pneumonia, conducted by Johnson & Johnson. One study compared doripenem with piperacillin/tazobactam in nonventilated patients with nosocomial pneumonia and those with early-onset VAP (occurring within the first 4 days of hospitalization). The second study compared doripenem to imipenem, another carbapenem antibiotic, in patients with early-onset VAP and late-onset VAP (occurring after 5 or more days of hospitalization).

Both studies were designed to establish “noninferiority” between doripenem and the other treatments, based on the clinical cure rate 6–20 days after treatment was completed. The clinical cure rate was defined as “complete resolution or marked improvement or return to baseline of all signs and symptoms of pneumonia and improvement or lack of progression of all chest x-ray abnormalities, such that no additional antibacterial therapy was required.”

In the study of patients with non-VAP and early-onset VAP, the clinical cure rates were 81.3% among those who received doripenem and 79.8% among those who received piperacillin/tazobactam. In the study of patients with early and late-onset VAP, the clinical cure rate was 68.3% among those treated with doripenem, compared with 64.8% of those who received imipenem. Adverse events were similar to those seen with doripenem for other approved indications, and with carbapenems, and “in general, was similar” to the adverse events in patients on the comparator antibiotics, according to the company.

ROCKVILLE, MD. — A Food and Drug Administration advisory panel was split on whether the efficacy and safety data on doripenem, an injectable, broad-spectrum antibiotic, were adequate to support its approval for treating nosocomial pneumonia including ventilator-associated pneumonia.

At a meeting of the FDA's Anti-Infective Drugs Advisory Committee, the panel voted 7 to 6 that the clinical efficacy data from two noninferiority studies comparing doripenem with other antibiotics supported approval of the drug for this indication. The panel voted 8 to 5 that doripenem was safe for treating patients with nosocomial pneumonia including ventilator-assisted pneumonia (VAP) based on the trial data.

Johnson & Johnson Pharmaceutical Research and Development has proposed that doripenem be approved for treating nosocomial pneumonia, including VAP.

Those voting against approval had concerns about the studies, which included irregularities in the data and excess mortality in patients in one of the two studies among doripenem-treated patients. Several of those voting yes said they were supporting approval with reservations, citing the same reasons.

Doripenem, marketed as Doribax, was approved in October 2007 for treating complicated urinary tract infections and complicated intra-abdominal infections. Doripenem is a carbapenem in the β-lactam class of antibacterial agents that has broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria, according to the company.

The data submitted for approval included two phase III, multicenter, randomized, open label, active control studies of adults with clinical, radiologic, and microbiologic evidence of nosocomial pneumonia, conducted by Johnson & Johnson. One study compared doripenem with piperacillin/tazobactam in nonventilated patients with nosocomial pneumonia and those with early-onset VAP (occurring within the first 4 days of hospitalization). The second study compared doripenem to imipenem, another carbapenem antibiotic, in patients with early-onset VAP and late-onset VAP (occurring after 5 or more days of hospitalization).

Both studies were designed to establish “noninferiority” between doripenem and the other treatments, based on the clinical cure rate 6–20 days after treatment was completed. The clinical cure rate was defined as “complete resolution or marked improvement or return to baseline of all signs and symptoms of pneumonia and improvement or lack of progression of all chest x-ray abnormalities, such that no additional antibacterial therapy was required.”

In the study of patients with non-VAP and early-onset VAP, the clinical cure rates were 81.3% among those who received doripenem and 79.8% among those who received piperacillin/tazobactam. In the study of patients with early and late-onset VAP, the clinical cure rate was 68.3% among those treated with doripenem, compared with 64.8% of those who received imipenem. Adverse events were similar to those seen with doripenem for other approved indications, and with carbapenems, and “in general, was similar” to the adverse events in patients on the comparator antibiotics, according to the company.

ROCKVILLE, MD. — A Food and Drug Administration advisory panel was split on whether the efficacy and safety data on doripenem, an injectable, broad-spectrum antibiotic, were adequate to support its approval for treating nosocomial pneumonia including ventilator-associated pneumonia.

At a meeting of the FDA's Anti-Infective Drugs Advisory Committee, the panel voted 7 to 6 that the clinical efficacy data from two noninferiority studies comparing doripenem with other antibiotics supported approval of the drug for this indication. The panel voted 8 to 5 that doripenem was safe for treating patients with nosocomial pneumonia including ventilator-assisted pneumonia (VAP) based on the trial data.

Johnson & Johnson Pharmaceutical Research and Development has proposed that doripenem be approved for treating nosocomial pneumonia, including VAP.

Those voting against approval had concerns about the studies, which included irregularities in the data and excess mortality in patients in one of the two studies among doripenem-treated patients. Several of those voting yes said they were supporting approval with reservations, citing the same reasons.

Doripenem, marketed as Doribax, was approved in October 2007 for treating complicated urinary tract infections and complicated intra-abdominal infections. Doripenem is a carbapenem in the β-lactam class of antibacterial agents that has broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria, according to the company.

The data submitted for approval included two phase III, multicenter, randomized, open label, active control studies of adults with clinical, radiologic, and microbiologic evidence of nosocomial pneumonia, conducted by Johnson & Johnson. One study compared doripenem with piperacillin/tazobactam in nonventilated patients with nosocomial pneumonia and those with early-onset VAP (occurring within the first 4 days of hospitalization). The second study compared doripenem to imipenem, another carbapenem antibiotic, in patients with early-onset VAP and late-onset VAP (occurring after 5 or more days of hospitalization).

Both studies were designed to establish “noninferiority” between doripenem and the other treatments, based on the clinical cure rate 6–20 days after treatment was completed. The clinical cure rate was defined as “complete resolution or marked improvement or return to baseline of all signs and symptoms of pneumonia and improvement or lack of progression of all chest x-ray abnormalities, such that no additional antibacterial therapy was required.”

In the study of patients with non-VAP and early-onset VAP, the clinical cure rates were 81.3% among those who received doripenem and 79.8% among those who received piperacillin/tazobactam. In the study of patients with early and late-onset VAP, the clinical cure rate was 68.3% among those treated with doripenem, compared with 64.8% of those who received imipenem. Adverse events were similar to those seen with doripenem for other approved indications, and with carbapenems, and “in general, was similar” to the adverse events in patients on the comparator antibiotics, according to the company.

The rate of postoperative sepsis among adult patients increased significantly over a 17-year period, as did the proportion of cases that were considered severe, according to an analysis of a state inpatient database.

Although hospital mortality from postoperative sepsis dropped in patients undergoing nonelective surgery, the proportion of patients who developed severe sepsis after elective surgery increased significantly, and mortality from sepsis after elective surgery did not improve, Dr. Todd Vogel said. He presented results of the study at the annual meeting of the Surgical Infection Society.

“What's concerning from the data is that elective cases did not show a significant decreased trend at all; in fact, we have not made any headway in mortality secondary to sepsis” after elective surgery, said Dr. Vogel, of the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick.

Dr. Vogel and his associates analyzed data from the State Inpatient Database for New Jersey from 1990 to 2006 for patients aged 18 and older who developed sepsis after elective or nonelective surgery, using diagnosis codes defined by the Agency for Healthcare Research and Quality. There were 1,276,451 surgery discharges during that time, of which 42% were elective and 58% were nonelective. Sepsis was a complication in 3% of all surgical procedures.

Of the patients undergoing elective surgery, about 1% developed postoperative sepsis and 0.5% developed severe sepsis (defined as sepsis complicated by organ dysfunction). The rate of sepsis after elective surgery increased from 0.67% to 1.74%, and the rate of severe sepsis increased from 0.22% to 1.12%. Both were highly statistically significant increases. The proportion of sepsis cases that were severe after elective surgery nearly doubled from 33% to 65%, also a highly significant increase.

The rates of postoperative sepsis and severe sepsis were significantly higher among the patients who had nonelective surgery (about 4% for sepsis and about 2% for severe sepsis). The rate of sepsis after nonelective surgical procedures increased from 3.7% to 4.5%, and the rate of severe sepsis increased from 1.8% to about 3%. The proportion of sepsis cases after nonelective surgery that were severe increased significantly from almost 48% to nearly 70%. However, in-hospital mortality among these patients dropped from 38% to 30% for sepsis and from 55% to 38% for severe sepsis, a highly significant decrease.

The pattern of pathogens also changed during the period studied, with a significant drop in rates of septicemia caused by staphylococci, anaerobes, pseudomonas, and Escherichia coli among the nonelective surgery cohort. There was also a significant increase in the rates of streptococcal septicemia and staphylococcal septicemia in a subgroup of patients undergoing elective surgery, but the rates of septicemia caused by E. coli, pseudomonas, and anaerobes remained unchanged in this cohort.

The findings may be explained by changes in the types of patients who are admitted to the hospital for elective surgery, Dr. Vogel said in an interview. The trend toward minimally invasive procedures may mean that elderly patients or those who are sicker are more likely to be admitted to the hospital for elective surgery, he speculated. The improved mortality among nonelective cases could be attributable to advances in critical care and antibiotics, and greater awareness of sepsis, he added, noting that this was not clear from the data and will be the focus of a future study.

The investigators also found a significant disparity based on ethnicity, gender, and age of patients, which Dr. Vogel said needs to be studied further. The rates of postoperative sepsis and mortality after nonelective and elective surgery were highest among black patients, compared with white patients (who had the lowest rates) and Hispanic patients. Men were more likely to have postoperative sepsis than were women, and there was a significant increase in the rates of postoperative sepsis with age.

The rate of postoperative sepsis among adult patients increased significantly over a 17-year period, as did the proportion of cases that were considered severe, according to an analysis of a state inpatient database.

Although hospital mortality from postoperative sepsis dropped in patients undergoing nonelective surgery, the proportion of patients who developed severe sepsis after elective surgery increased significantly, and mortality from sepsis after elective surgery did not improve, Dr. Todd Vogel said. He presented results of the study at the annual meeting of the Surgical Infection Society.

“What's concerning from the data is that elective cases did not show a significant decreased trend at all; in fact, we have not made any headway in mortality secondary to sepsis” after elective surgery, said Dr. Vogel, of the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick.

Dr. Vogel and his associates analyzed data from the State Inpatient Database for New Jersey from 1990 to 2006 for patients aged 18 and older who developed sepsis after elective or nonelective surgery, using diagnosis codes defined by the Agency for Healthcare Research and Quality. There were 1,276,451 surgery discharges during that time, of which 42% were elective and 58% were nonelective. Sepsis was a complication in 3% of all surgical procedures.

Of the patients undergoing elective surgery, about 1% developed postoperative sepsis and 0.5% developed severe sepsis (defined as sepsis complicated by organ dysfunction). The rate of sepsis after elective surgery increased from 0.67% to 1.74%, and the rate of severe sepsis increased from 0.22% to 1.12%. Both were highly statistically significant increases. The proportion of sepsis cases that were severe after elective surgery nearly doubled from 33% to 65%, also a highly significant increase.

The rates of postoperative sepsis and severe sepsis were significantly higher among the patients who had nonelective surgery (about 4% for sepsis and about 2% for severe sepsis). The rate of sepsis after nonelective surgical procedures increased from 3.7% to 4.5%, and the rate of severe sepsis increased from 1.8% to about 3%. The proportion of sepsis cases after nonelective surgery that were severe increased significantly from almost 48% to nearly 70%. However, in-hospital mortality among these patients dropped from 38% to 30% for sepsis and from 55% to 38% for severe sepsis, a highly significant decrease.

The pattern of pathogens also changed during the period studied, with a significant drop in rates of septicemia caused by staphylococci, anaerobes, pseudomonas, and Escherichia coli among the nonelective surgery cohort. There was also a significant increase in the rates of streptococcal septicemia and staphylococcal septicemia in a subgroup of patients undergoing elective surgery, but the rates of septicemia caused by E. coli, pseudomonas, and anaerobes remained unchanged in this cohort.

The findings may be explained by changes in the types of patients who are admitted to the hospital for elective surgery, Dr. Vogel said in an interview. The trend toward minimally invasive procedures may mean that elderly patients or those who are sicker are more likely to be admitted to the hospital for elective surgery, he speculated. The improved mortality among nonelective cases could be attributable to advances in critical care and antibiotics, and greater awareness of sepsis, he added, noting that this was not clear from the data and will be the focus of a future study.

The investigators also found a significant disparity based on ethnicity, gender, and age of patients, which Dr. Vogel said needs to be studied further. The rates of postoperative sepsis and mortality after nonelective and elective surgery were highest among black patients, compared with white patients (who had the lowest rates) and Hispanic patients. Men were more likely to have postoperative sepsis than were women, and there was a significant increase in the rates of postoperative sepsis with age.

The rate of postoperative sepsis among adult patients increased significantly over a 17-year period, as did the proportion of cases that were considered severe, according to an analysis of a state inpatient database.

Although hospital mortality from postoperative sepsis dropped in patients undergoing nonelective surgery, the proportion of patients who developed severe sepsis after elective surgery increased significantly, and mortality from sepsis after elective surgery did not improve, Dr. Todd Vogel said. He presented results of the study at the annual meeting of the Surgical Infection Society.

“What's concerning from the data is that elective cases did not show a significant decreased trend at all; in fact, we have not made any headway in mortality secondary to sepsis” after elective surgery, said Dr. Vogel, of the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick.

Dr. Vogel and his associates analyzed data from the State Inpatient Database for New Jersey from 1990 to 2006 for patients aged 18 and older who developed sepsis after elective or nonelective surgery, using diagnosis codes defined by the Agency for Healthcare Research and Quality. There were 1,276,451 surgery discharges during that time, of which 42% were elective and 58% were nonelective. Sepsis was a complication in 3% of all surgical procedures.

Of the patients undergoing elective surgery, about 1% developed postoperative sepsis and 0.5% developed severe sepsis (defined as sepsis complicated by organ dysfunction). The rate of sepsis after elective surgery increased from 0.67% to 1.74%, and the rate of severe sepsis increased from 0.22% to 1.12%. Both were highly statistically significant increases. The proportion of sepsis cases that were severe after elective surgery nearly doubled from 33% to 65%, also a highly significant increase.

The rates of postoperative sepsis and severe sepsis were significantly higher among the patients who had nonelective surgery (about 4% for sepsis and about 2% for severe sepsis). The rate of sepsis after nonelective surgical procedures increased from 3.7% to 4.5%, and the rate of severe sepsis increased from 1.8% to about 3%. The proportion of sepsis cases after nonelective surgery that were severe increased significantly from almost 48% to nearly 70%. However, in-hospital mortality among these patients dropped from 38% to 30% for sepsis and from 55% to 38% for severe sepsis, a highly significant decrease.

The pattern of pathogens also changed during the period studied, with a significant drop in rates of septicemia caused by staphylococci, anaerobes, pseudomonas, and Escherichia coli among the nonelective surgery cohort. There was also a significant increase in the rates of streptococcal septicemia and staphylococcal septicemia in a subgroup of patients undergoing elective surgery, but the rates of septicemia caused by E. coli, pseudomonas, and anaerobes remained unchanged in this cohort.

The findings may be explained by changes in the types of patients who are admitted to the hospital for elective surgery, Dr. Vogel said in an interview. The trend toward minimally invasive procedures may mean that elderly patients or those who are sicker are more likely to be admitted to the hospital for elective surgery, he speculated. The improved mortality among nonelective cases could be attributable to advances in critical care and antibiotics, and greater awareness of sepsis, he added, noting that this was not clear from the data and will be the focus of a future study.

The investigators also found a significant disparity based on ethnicity, gender, and age of patients, which Dr. Vogel said needs to be studied further. The rates of postoperative sepsis and mortality after nonelective and elective surgery were highest among black patients, compared with white patients (who had the lowest rates) and Hispanic patients. Men were more likely to have postoperative sepsis than were women, and there was a significant increase in the rates of postoperative sepsis with age.

Three-year data on surgical patients in Pennsylvania support using surgeon and hospital volume as part of the credentialing process for bariatric surgery centers of excellence, according to a study of 14,716 patients who underwent bariatric surgery in Pennsylvania hospitals from 2000 to 2003.

Dr. Ann M. Rogers and her associates at Pennsylvania State University, Hershey, analyzed the relationship between surgeon and hospital volume on length of stay, in-hospital mortality, and 30-day mortality after adjusting for age, gender, ethnicity, payer, and score based on the severity of the patients' illness.

They found that bariatric surgery “performed by high-volume surgeons in hospitals where more than 100 cases were performed a year was associated with decreased mortality and length of stay, compared to those patients whose surgeons operated on fewer than 100 cases per year at hospitals with fewer than 100 cases per year.”

Individual surgeons and hospitals were stratified into one of three categories: high volume (more than 100 cases per year), medium volume (50–100 cases per year), or low volume (fewer than 50 cases per year).

During the time period of the study, which was presented at the Academic Surgical Congress, the mean surgical volume per hospital increased from 20 to 120 cases per year, and in-hospital mortality decreased from 0.8% to 0.2%. Overall, 30-day mortality was 1.15%, and in-hospital mortality was 0.37%.

After controlling for other factors, the investigators found that 30-day mortality was 3.7 times higher among those treated by low-volume surgeons and 2.8 times higher among those treated by medium-volume surgeons, when compared with those treated by high-volume surgeons, which were significant differences.

In addition, 30-day mortality was 2.3 times greater for patients treated in low-volume hospitals and 1.6 times greater in medium-volume hospitals than in high-volume hospitals, which were significant differences.

Length of stay was significantly shorter in high-volume hospitals than in low- or medium-volume hospitals. “Our data showed progressively increasing length of stay from high- to medium- to low-volume hospitals and surgeons,” Dr. Rogers said in an interview.

Medium-volume hospitals and surgeons were associated with about half a day longer length of stay, while low-volume hospitals and surgeons were associated with about an additional day and a half in the hospital, compared with those in the high-volume hospital and surgeon group, said Dr. Rogers, director of the Penn State surgical weight loss program.

Male gender and admission severity, as well as hospital and surgeon volume, were significantly associated with increased in-hospital and 30-day mortality. Men were at a 3.6 times greater risk for in-hospital and 30-day mortality, compared with women, which was significant, she said.

Dr. Rogers of the department of surgery at the Penn State Milton S. Hershey Medical Center, Hershey, said there is a fairly large body of literature looking at the impact of surgeon and hospital volume on the outcomes of bariatric surgery, but that the Penn State group, spearheaded by Dr. Robert N. Cooney, is only the third to evaluate 30-day mortality, rather than in-hospital mortality alone.

Since 2006, when the Centers for Medicare and Medicaid Services decided to cover bariatric surgery performed at centers listed with the American Society for Bariatric Surgery/Surgical Review Corporation Center of Excellence or as an American College of Surgeons Level One Center of Excellence, hospitals have been under increased pressure to obtain bariatric surgery credentials.

As a result, many third-party payers either require that patients be treated only in credentialed centers or have created their own criteria for a center of excellence, Dr. Rogers noted. Surgeon and hospital volume are both considered in the credentialing process, and “we believe our results support the use of such criteria in the credentialing process” of both hospitals and surgeons, she said.

Studies of other surgical procedures have demonstrated higher morbidity and mortality associated with low-volume surgeons and hospitals, Dr. Myriam Curet said in an interview. The Penn State study confirms the finding that the relationship between volume and patient outcomes is also true for bariatric surgery, said Dr. Curet, a bariatric surgeon and professor of surgery at Stanford (Calif.) University.

This type of evidence was the impetus behind using the volume criteria for centers of excellence certification, “and this study confirms that this was the correct decision,” she added. “If we're all aiming to improve patient outcomes, then having these kinds of volume criteria to designate centers of excellence is clearly important.”

Three-year data on surgical patients in Pennsylvania support using surgeon and hospital volume as part of the credentialing process for bariatric surgery centers of excellence, according to a study of 14,716 patients who underwent bariatric surgery in Pennsylvania hospitals from 2000 to 2003.

Dr. Ann M. Rogers and her associates at Pennsylvania State University, Hershey, analyzed the relationship between surgeon and hospital volume on length of stay, in-hospital mortality, and 30-day mortality after adjusting for age, gender, ethnicity, payer, and score based on the severity of the patients' illness.

They found that bariatric surgery “performed by high-volume surgeons in hospitals where more than 100 cases were performed a year was associated with decreased mortality and length of stay, compared to those patients whose surgeons operated on fewer than 100 cases per year at hospitals with fewer than 100 cases per year.”

Individual surgeons and hospitals were stratified into one of three categories: high volume (more than 100 cases per year), medium volume (50–100 cases per year), or low volume (fewer than 50 cases per year).

During the time period of the study, which was presented at the Academic Surgical Congress, the mean surgical volume per hospital increased from 20 to 120 cases per year, and in-hospital mortality decreased from 0.8% to 0.2%. Overall, 30-day mortality was 1.15%, and in-hospital mortality was 0.37%.

After controlling for other factors, the investigators found that 30-day mortality was 3.7 times higher among those treated by low-volume surgeons and 2.8 times higher among those treated by medium-volume surgeons, when compared with those treated by high-volume surgeons, which were significant differences.

In addition, 30-day mortality was 2.3 times greater for patients treated in low-volume hospitals and 1.6 times greater in medium-volume hospitals than in high-volume hospitals, which were significant differences.

Length of stay was significantly shorter in high-volume hospitals than in low- or medium-volume hospitals. “Our data showed progressively increasing length of stay from high- to medium- to low-volume hospitals and surgeons,” Dr. Rogers said in an interview.

Medium-volume hospitals and surgeons were associated with about half a day longer length of stay, while low-volume hospitals and surgeons were associated with about an additional day and a half in the hospital, compared with those in the high-volume hospital and surgeon group, said Dr. Rogers, director of the Penn State surgical weight loss program.

Male gender and admission severity, as well as hospital and surgeon volume, were significantly associated with increased in-hospital and 30-day mortality. Men were at a 3.6 times greater risk for in-hospital and 30-day mortality, compared with women, which was significant, she said.

Dr. Rogers of the department of surgery at the Penn State Milton S. Hershey Medical Center, Hershey, said there is a fairly large body of literature looking at the impact of surgeon and hospital volume on the outcomes of bariatric surgery, but that the Penn State group, spearheaded by Dr. Robert N. Cooney, is only the third to evaluate 30-day mortality, rather than in-hospital mortality alone.

Since 2006, when the Centers for Medicare and Medicaid Services decided to cover bariatric surgery performed at centers listed with the American Society for Bariatric Surgery/Surgical Review Corporation Center of Excellence or as an American College of Surgeons Level One Center of Excellence, hospitals have been under increased pressure to obtain bariatric surgery credentials.

As a result, many third-party payers either require that patients be treated only in credentialed centers or have created their own criteria for a center of excellence, Dr. Rogers noted. Surgeon and hospital volume are both considered in the credentialing process, and “we believe our results support the use of such criteria in the credentialing process” of both hospitals and surgeons, she said.

Studies of other surgical procedures have demonstrated higher morbidity and mortality associated with low-volume surgeons and hospitals, Dr. Myriam Curet said in an interview. The Penn State study confirms the finding that the relationship between volume and patient outcomes is also true for bariatric surgery, said Dr. Curet, a bariatric surgeon and professor of surgery at Stanford (Calif.) University.

This type of evidence was the impetus behind using the volume criteria for centers of excellence certification, “and this study confirms that this was the correct decision,” she added. “If we're all aiming to improve patient outcomes, then having these kinds of volume criteria to designate centers of excellence is clearly important.”

Three-year data on surgical patients in Pennsylvania support using surgeon and hospital volume as part of the credentialing process for bariatric surgery centers of excellence, according to a study of 14,716 patients who underwent bariatric surgery in Pennsylvania hospitals from 2000 to 2003.

Dr. Ann M. Rogers and her associates at Pennsylvania State University, Hershey, analyzed the relationship between surgeon and hospital volume on length of stay, in-hospital mortality, and 30-day mortality after adjusting for age, gender, ethnicity, payer, and score based on the severity of the patients' illness.

They found that bariatric surgery “performed by high-volume surgeons in hospitals where more than 100 cases were performed a year was associated with decreased mortality and length of stay, compared to those patients whose surgeons operated on fewer than 100 cases per year at hospitals with fewer than 100 cases per year.”

Individual surgeons and hospitals were stratified into one of three categories: high volume (more than 100 cases per year), medium volume (50–100 cases per year), or low volume (fewer than 50 cases per year).

During the time period of the study, which was presented at the Academic Surgical Congress, the mean surgical volume per hospital increased from 20 to 120 cases per year, and in-hospital mortality decreased from 0.8% to 0.2%. Overall, 30-day mortality was 1.15%, and in-hospital mortality was 0.37%.

After controlling for other factors, the investigators found that 30-day mortality was 3.7 times higher among those treated by low-volume surgeons and 2.8 times higher among those treated by medium-volume surgeons, when compared with those treated by high-volume surgeons, which were significant differences.

In addition, 30-day mortality was 2.3 times greater for patients treated in low-volume hospitals and 1.6 times greater in medium-volume hospitals than in high-volume hospitals, which were significant differences.

Length of stay was significantly shorter in high-volume hospitals than in low- or medium-volume hospitals. “Our data showed progressively increasing length of stay from high- to medium- to low-volume hospitals and surgeons,” Dr. Rogers said in an interview.

Medium-volume hospitals and surgeons were associated with about half a day longer length of stay, while low-volume hospitals and surgeons were associated with about an additional day and a half in the hospital, compared with those in the high-volume hospital and surgeon group, said Dr. Rogers, director of the Penn State surgical weight loss program.

Male gender and admission severity, as well as hospital and surgeon volume, were significantly associated with increased in-hospital and 30-day mortality. Men were at a 3.6 times greater risk for in-hospital and 30-day mortality, compared with women, which was significant, she said.

Dr. Rogers of the department of surgery at the Penn State Milton S. Hershey Medical Center, Hershey, said there is a fairly large body of literature looking at the impact of surgeon and hospital volume on the outcomes of bariatric surgery, but that the Penn State group, spearheaded by Dr. Robert N. Cooney, is only the third to evaluate 30-day mortality, rather than in-hospital mortality alone.

Since 2006, when the Centers for Medicare and Medicaid Services decided to cover bariatric surgery performed at centers listed with the American Society for Bariatric Surgery/Surgical Review Corporation Center of Excellence or as an American College of Surgeons Level One Center of Excellence, hospitals have been under increased pressure to obtain bariatric surgery credentials.

As a result, many third-party payers either require that patients be treated only in credentialed centers or have created their own criteria for a center of excellence, Dr. Rogers noted. Surgeon and hospital volume are both considered in the credentialing process, and “we believe our results support the use of such criteria in the credentialing process” of both hospitals and surgeons, she said.

Studies of other surgical procedures have demonstrated higher morbidity and mortality associated with low-volume surgeons and hospitals, Dr. Myriam Curet said in an interview. The Penn State study confirms the finding that the relationship between volume and patient outcomes is also true for bariatric surgery, said Dr. Curet, a bariatric surgeon and professor of surgery at Stanford (Calif.) University.

This type of evidence was the impetus behind using the volume criteria for centers of excellence certification, “and this study confirms that this was the correct decision,” she added. “If we're all aiming to improve patient outcomes, then having these kinds of volume criteria to designate centers of excellence is clearly important.”

The letter is available at www.fda.gov/medwatch/safety/2008/safety08.htm#Relenzawww.fda.gov/medwatch

Information about neuropsychiatric events associated with zanamivir in people being treated for influenza was added to the warnings and precautions section of the antiviral drug's label.

The addition reflects postmarketing reports of delirium and abnormal behavior in patients with influenza taking neuraminidase inhibitors, including zanamivir (Relenza, GlaxoSmithKline). Some of the cases resulted in fatalities related to self-injurious behavior.

The addition is described in a Dear Healthcare Professional letter from GSK, and in a notice on the Food and Drug Administration's MedWatch site.

Most of the reports have been from Japan, primarily among pediatric patients, and events “often had an abrupt onset and rapid resolution,” the revised labeling says. The label says that the contribution of zanamivir to these events “has not been established” and points out that influenza also can be associated with various neurologic and behavioral symptoms, including seizures, hallucinations, delirium, and abnormal behavior, which in some cases can be fatal.

The incidence of these adverse events cannot be estimated because the reports were voluntary, “but they appear to be uncommon based on usage data for Relenza,” the label says.

Neuropsychiatric events associated with zanamivir and the other available neuraminidase inhibitor, oseltamivir (Tamiflu), were discussed at a meeting of the FDA's Pediatric Advisory Committee, and the panel narrowly recommended revising the labeling for both drugs to include information about these events.

The letter is available at www.fda.gov/medwatch/safety/2008/safety08.htm#Relenzawww.fda.gov/medwatch

Information about neuropsychiatric events associated with zanamivir in people being treated for influenza was added to the warnings and precautions section of the antiviral drug's label.

The addition reflects postmarketing reports of delirium and abnormal behavior in patients with influenza taking neuraminidase inhibitors, including zanamivir (Relenza, GlaxoSmithKline). Some of the cases resulted in fatalities related to self-injurious behavior.

The addition is described in a Dear Healthcare Professional letter from GSK, and in a notice on the Food and Drug Administration's MedWatch site.

Most of the reports have been from Japan, primarily among pediatric patients, and events “often had an abrupt onset and rapid resolution,” the revised labeling says. The label says that the contribution of zanamivir to these events “has not been established” and points out that influenza also can be associated with various neurologic and behavioral symptoms, including seizures, hallucinations, delirium, and abnormal behavior, which in some cases can be fatal.

The incidence of these adverse events cannot be estimated because the reports were voluntary, “but they appear to be uncommon based on usage data for Relenza,” the label says.

Neuropsychiatric events associated with zanamivir and the other available neuraminidase inhibitor, oseltamivir (Tamiflu), were discussed at a meeting of the FDA's Pediatric Advisory Committee, and the panel narrowly recommended revising the labeling for both drugs to include information about these events.

The letter is available at www.fda.gov/medwatch/safety/2008/safety08.htm#Relenzawww.fda.gov/medwatch

Information about neuropsychiatric events associated with zanamivir in people being treated for influenza was added to the warnings and precautions section of the antiviral drug's label.

The addition reflects postmarketing reports of delirium and abnormal behavior in patients with influenza taking neuraminidase inhibitors, including zanamivir (Relenza, GlaxoSmithKline). Some of the cases resulted in fatalities related to self-injurious behavior.

The addition is described in a Dear Healthcare Professional letter from GSK, and in a notice on the Food and Drug Administration's MedWatch site.

Most of the reports have been from Japan, primarily among pediatric patients, and events “often had an abrupt onset and rapid resolution,” the revised labeling says. The label says that the contribution of zanamivir to these events “has not been established” and points out that influenza also can be associated with various neurologic and behavioral symptoms, including seizures, hallucinations, delirium, and abnormal behavior, which in some cases can be fatal.

The incidence of these adverse events cannot be estimated because the reports were voluntary, “but they appear to be uncommon based on usage data for Relenza,” the label says.

Neuropsychiatric events associated with zanamivir and the other available neuraminidase inhibitor, oseltamivir (Tamiflu), were discussed at a meeting of the FDA's Pediatric Advisory Committee, and the panel narrowly recommended revising the labeling for both drugs to include information about these events.

A protein linked to inflammation and tissue remodeling is a significant biomarker for asthma and poor lung function, and a variation in that protein's genetic code is also associated with asthma risk and bronchial hyperresponsiveness.

A single-nucleotide polymorphism (SNP) was associated with elevated serum levels of the protein, YKL-40, in several populations, and both the genetic variation and elevated YKL-40 levels were associated with asthma, bronchial hyperresponsiveness, and reduced lung function, according to Carol Ober, Ph.D., of the University of Chicago and her associates in the United States and Germany (N. Engl. J. Med. 2008;358:1682–91).

In an earlier study, some of the same investigators had reported that serum levels of YKL-40 were elevated in patients with asthma. Serum YKL-40 levels also were associated with asthma severity, thickness of the subepithelial basement membrane, and pulmonary function, suggesting that YKL-40 levels could be a biomarker for asthma.

The investigators conducted a genomewide association study in a group of 632 related Hutterites aged 6–92 years (mean age 33) living on communal farms in South Dakota. They also included studies of children with and without asthma.

The Hutterites' mean YKL-40 levels were 15% higher among those with asthma and 10% higher among those with bronchial hyperresponsiveness, compared with controls. They also found a significant association between an SNP in CHI3L1, a gene encoding for YKL-40, and elevated serum YKL-40 levels, asthma, bronchial hyperresponsiveness, and measures of pulmonary function.

The researchers also determined that the same SNP was predictive of asthma from birth through age 5 years in a study of 638 German children at about age 10 years, and in a study of 296 adults and children in Chicago.

The result “shows that serum YKL-40 level is a highly heritable, quantitative trait in humans and confirms that YKL-40 is a significant biomarker for asthma susceptibility and reduced lung function,” the authors wrote. Genetic variation in CHI3L1 “influences serum YKL-40 levels and is associated with the risk of asthma, bronchial hyperresponsiveness, and reduced lung function.”

Identifying the rest of the genetic loci that contribute to the differences in serum YKL-40 levels and related proteins “could identify additional genes with a significant effect on the risk of asthma and lung function,” the researchers added.

These results need to be confirmed with large studies, Miriam Moffatt, D.Phil., and Dr. William O.C.M. Cookson of the National Heart and Lung Institute at Imperial College London, said in an accompanying editorial (N. Engl. J. Med. 2008;358:1725–6).

A protein linked to inflammation and tissue remodeling is a significant biomarker for asthma and poor lung function, and a variation in that protein's genetic code is also associated with asthma risk and bronchial hyperresponsiveness.

A single-nucleotide polymorphism (SNP) was associated with elevated serum levels of the protein, YKL-40, in several populations, and both the genetic variation and elevated YKL-40 levels were associated with asthma, bronchial hyperresponsiveness, and reduced lung function, according to Carol Ober, Ph.D., of the University of Chicago and her associates in the United States and Germany (N. Engl. J. Med. 2008;358:1682–91).

In an earlier study, some of the same investigators had reported that serum levels of YKL-40 were elevated in patients with asthma. Serum YKL-40 levels also were associated with asthma severity, thickness of the subepithelial basement membrane, and pulmonary function, suggesting that YKL-40 levels could be a biomarker for asthma.

The investigators conducted a genomewide association study in a group of 632 related Hutterites aged 6–92 years (mean age 33) living on communal farms in South Dakota. They also included studies of children with and without asthma.

The Hutterites' mean YKL-40 levels were 15% higher among those with asthma and 10% higher among those with bronchial hyperresponsiveness, compared with controls. They also found a significant association between an SNP in CHI3L1, a gene encoding for YKL-40, and elevated serum YKL-40 levels, asthma, bronchial hyperresponsiveness, and measures of pulmonary function.

The researchers also determined that the same SNP was predictive of asthma from birth through age 5 years in a study of 638 German children at about age 10 years, and in a study of 296 adults and children in Chicago.

The result “shows that serum YKL-40 level is a highly heritable, quantitative trait in humans and confirms that YKL-40 is a significant biomarker for asthma susceptibility and reduced lung function,” the authors wrote. Genetic variation in CHI3L1 “influences serum YKL-40 levels and is associated with the risk of asthma, bronchial hyperresponsiveness, and reduced lung function.”

Identifying the rest of the genetic loci that contribute to the differences in serum YKL-40 levels and related proteins “could identify additional genes with a significant effect on the risk of asthma and lung function,” the researchers added.

These results need to be confirmed with large studies, Miriam Moffatt, D.Phil., and Dr. William O.C.M. Cookson of the National Heart and Lung Institute at Imperial College London, said in an accompanying editorial (N. Engl. J. Med. 2008;358:1725–6).

A protein linked to inflammation and tissue remodeling is a significant biomarker for asthma and poor lung function, and a variation in that protein's genetic code is also associated with asthma risk and bronchial hyperresponsiveness.

A single-nucleotide polymorphism (SNP) was associated with elevated serum levels of the protein, YKL-40, in several populations, and both the genetic variation and elevated YKL-40 levels were associated with asthma, bronchial hyperresponsiveness, and reduced lung function, according to Carol Ober, Ph.D., of the University of Chicago and her associates in the United States and Germany (N. Engl. J. Med. 2008;358:1682–91).

In an earlier study, some of the same investigators had reported that serum levels of YKL-40 were elevated in patients with asthma. Serum YKL-40 levels also were associated with asthma severity, thickness of the subepithelial basement membrane, and pulmonary function, suggesting that YKL-40 levels could be a biomarker for asthma.

The investigators conducted a genomewide association study in a group of 632 related Hutterites aged 6–92 years (mean age 33) living on communal farms in South Dakota. They also included studies of children with and without asthma.

The Hutterites' mean YKL-40 levels were 15% higher among those with asthma and 10% higher among those with bronchial hyperresponsiveness, compared with controls. They also found a significant association between an SNP in CHI3L1, a gene encoding for YKL-40, and elevated serum YKL-40 levels, asthma, bronchial hyperresponsiveness, and measures of pulmonary function.

The researchers also determined that the same SNP was predictive of asthma from birth through age 5 years in a study of 638 German children at about age 10 years, and in a study of 296 adults and children in Chicago.

The result “shows that serum YKL-40 level is a highly heritable, quantitative trait in humans and confirms that YKL-40 is a significant biomarker for asthma susceptibility and reduced lung function,” the authors wrote. Genetic variation in CHI3L1 “influences serum YKL-40 levels and is associated with the risk of asthma, bronchial hyperresponsiveness, and reduced lung function.”

Identifying the rest of the genetic loci that contribute to the differences in serum YKL-40 levels and related proteins “could identify additional genes with a significant effect on the risk of asthma and lung function,” the researchers added.

These results need to be confirmed with large studies, Miriam Moffatt, D.Phil., and Dr. William O.C.M. Cookson of the National Heart and Lung Institute at Imperial College London, said in an accompanying editorial (N. Engl. J. Med. 2008;358:1725–6).

Difficult life events and other types of stress, as well as psychological interventions, can have a marked impact on the occurrence of athletic injuries among children and adolescents, according to the authors of a review on the topic.

These issues also can affect the way in which children and adolescents recover and subsequently perform in sports, the authors wrote.

Awareness of psychosocial stressors “unique to young athletes that may contribute to injury occurrence and influence rehabilitation may help counter the negative effects and unhealthy behavioral responses that sometimes occur post injury,” said Angela H. Nippert, Ph.D., and Aynsley M. Smith, Ph.D., in the May issue of Physical Medicine and Rehabilitation Clinics of North America.

Dr. Nippert is with the department of kinesiology and health sciences, Concordia University, St. Paul, Minn.; Dr. Smith is with the Mayo Clinic Sports Medicine Center and the department of orthopedic surgery and physical medicine and rehabilitation at Mayo Medical School, Rochester, Minn.

Dr. Nippert and Dr. Smith also recommend that medical professionals be aware that even though they might be considered the least likely person involved with an injured athlete to pressure the athlete to return to participation before a full recovery, they may not be immune to the “culture of risk,” in which playing a sport despite continuing pain and injury is acceptable.

To help maintain objectivity, it is important to be aware of the influence this culture of risk might have on decisions about injured athletes, the authors wrote. Other factors, such as whether an athlete is a starter, the time in the season, and their own experiences with competing and training also can influence their decisions, the authors added (Phys. Med. Rehabil. Clin. N. Am. 2008;19:399–418).

Psychosocial factors that can affect child and adolescent athletes before and after an injury include athletic identity, body image, and life stressors, such as a parent's divorce. A stressful situation can increase the risk of sustaining an injury when, for example, it interferes with attention.

The authors cite several studies of different types of young athletes that have found an association between stressful life events and increased risk of sustaining injuries. Stress and coping resources, in addition to the stress of an injury, also can affect athletes after an injury.

As an example, the authors described a 14-year-old basketball player who sustained a severe ankle sprain after the divorce of his parents and missed out on a full season. He became alienated from the team, which had provided support during the divorce. Because his only coping skills were connected to sports, he gave up on physical rehabilitation, and started to experiment with alcohol, marijuana, and sex. But a sports psychology counselor helped the athlete resume involvement in athletics and other activities that helped him improve his behavior and self-esteem.

The damage an injury can do to a young athlete's self-esteem also can increase their risk for a mood disturbance, particularly if the athlete strongly identifies with a sport, according to the authors.

Dr. Nippert and Dr. Smith also cite data suggesting that mood disturbances start immediately after the injury and begin to ebb as athletes feel they are recovering.

However, mood might not return to baseline in some athletes, the authors pointed out, adding, “mood disturbance is a concern for adolescents and young adults who are already at approximately three times greater risk for suicide than the general population.”

When evaluating a young athlete with an injury, medical professionals should be aware of their psychological responses after the injury and during rehabilitation, they advised, noting that “changes in affect, energy, sleep patterns, eye contact, commitment to rehabilitation, and hygiene may be flags for concern.”

They also recommend looking out for signs of an eating disorder, which can affect male and female athletes after an injury, and the use of performance enhancing substances.

Sports injuries among children and adolescents can be very stressful–even if they are minor–but treatment often focuses only on the physical aspects of the injury, not the stress associated with the injury and the recovery period.

If not recognized or addressed, this stress can affect recovery and performance when the individual resumes full participation in the sport, the authors observed.

Psychological interventions that can help athletes cope with psychosocial stressors and improve mood include setting short, intermediate, and long-term goals for rehabilitation and for returning to sports, such as daily goals of icing the injury, elevating the injured area, and managing pain, the authors recommended.

Other interventions that have been reported to help during recovery from a sports injury are the use of relaxation and mental imagery.

“Through awareness and appropriate interventions, medical professionals can help facilitate an optimal physical and physiologic recovery” in young athletes who have sustained a sports injury, Dr. Nippert and Dr. Smith concluded.

Difficult life events and other types of stress, as well as psychological interventions, can have a marked impact on the occurrence of athletic injuries among children and adolescents, according to the authors of a review on the topic.

These issues also can affect the way in which children and adolescents recover and subsequently perform in sports, the authors wrote.

Awareness of psychosocial stressors “unique to young athletes that may contribute to injury occurrence and influence rehabilitation may help counter the negative effects and unhealthy behavioral responses that sometimes occur post injury,” said Angela H. Nippert, Ph.D., and Aynsley M. Smith, Ph.D., in the May issue of Physical Medicine and Rehabilitation Clinics of North America.

Dr. Nippert is with the department of kinesiology and health sciences, Concordia University, St. Paul, Minn.; Dr. Smith is with the Mayo Clinic Sports Medicine Center and the department of orthopedic surgery and physical medicine and rehabilitation at Mayo Medical School, Rochester, Minn.

Dr. Nippert and Dr. Smith also recommend that medical professionals be aware that even though they might be considered the least likely person involved with an injured athlete to pressure the athlete to return to participation before a full recovery, they may not be immune to the “culture of risk,” in which playing a sport despite continuing pain and injury is acceptable.

To help maintain objectivity, it is important to be aware of the influence this culture of risk might have on decisions about injured athletes, the authors wrote. Other factors, such as whether an athlete is a starter, the time in the season, and their own experiences with competing and training also can influence their decisions, the authors added (Phys. Med. Rehabil. Clin. N. Am. 2008;19:399–418).

Psychosocial factors that can affect child and adolescent athletes before and after an injury include athletic identity, body image, and life stressors, such as a parent's divorce. A stressful situation can increase the risk of sustaining an injury when, for example, it interferes with attention.

The authors cite several studies of different types of young athletes that have found an association between stressful life events and increased risk of sustaining injuries. Stress and coping resources, in addition to the stress of an injury, also can affect athletes after an injury.

As an example, the authors described a 14-year-old basketball player who sustained a severe ankle sprain after the divorce of his parents and missed out on a full season. He became alienated from the team, which had provided support during the divorce. Because his only coping skills were connected to sports, he gave up on physical rehabilitation, and started to experiment with alcohol, marijuana, and sex. But a sports psychology counselor helped the athlete resume involvement in athletics and other activities that helped him improve his behavior and self-esteem.

The damage an injury can do to a young athlete's self-esteem also can increase their risk for a mood disturbance, particularly if the athlete strongly identifies with a sport, according to the authors.

Dr. Nippert and Dr. Smith also cite data suggesting that mood disturbances start immediately after the injury and begin to ebb as athletes feel they are recovering.

However, mood might not return to baseline in some athletes, the authors pointed out, adding, “mood disturbance is a concern for adolescents and young adults who are already at approximately three times greater risk for suicide than the general population.”

When evaluating a young athlete with an injury, medical professionals should be aware of their psychological responses after the injury and during rehabilitation, they advised, noting that “changes in affect, energy, sleep patterns, eye contact, commitment to rehabilitation, and hygiene may be flags for concern.”

They also recommend looking out for signs of an eating disorder, which can affect male and female athletes after an injury, and the use of performance enhancing substances.

Sports injuries among children and adolescents can be very stressful–even if they are minor–but treatment often focuses only on the physical aspects of the injury, not the stress associated with the injury and the recovery period.

If not recognized or addressed, this stress can affect recovery and performance when the individual resumes full participation in the sport, the authors observed.

Psychological interventions that can help athletes cope with psychosocial stressors and improve mood include setting short, intermediate, and long-term goals for rehabilitation and for returning to sports, such as daily goals of icing the injury, elevating the injured area, and managing pain, the authors recommended.

Other interventions that have been reported to help during recovery from a sports injury are the use of relaxation and mental imagery.

“Through awareness and appropriate interventions, medical professionals can help facilitate an optimal physical and physiologic recovery” in young athletes who have sustained a sports injury, Dr. Nippert and Dr. Smith concluded.

Difficult life events and other types of stress, as well as psychological interventions, can have a marked impact on the occurrence of athletic injuries among children and adolescents, according to the authors of a review on the topic.

These issues also can affect the way in which children and adolescents recover and subsequently perform in sports, the authors wrote.

Awareness of psychosocial stressors “unique to young athletes that may contribute to injury occurrence and influence rehabilitation may help counter the negative effects and unhealthy behavioral responses that sometimes occur post injury,” said Angela H. Nippert, Ph.D., and Aynsley M. Smith, Ph.D., in the May issue of Physical Medicine and Rehabilitation Clinics of North America.

Dr. Nippert is with the department of kinesiology and health sciences, Concordia University, St. Paul, Minn.; Dr. Smith is with the Mayo Clinic Sports Medicine Center and the department of orthopedic surgery and physical medicine and rehabilitation at Mayo Medical School, Rochester, Minn.

Dr. Nippert and Dr. Smith also recommend that medical professionals be aware that even though they might be considered the least likely person involved with an injured athlete to pressure the athlete to return to participation before a full recovery, they may not be immune to the “culture of risk,” in which playing a sport despite continuing pain and injury is acceptable.

To help maintain objectivity, it is important to be aware of the influence this culture of risk might have on decisions about injured athletes, the authors wrote. Other factors, such as whether an athlete is a starter, the time in the season, and their own experiences with competing and training also can influence their decisions, the authors added (Phys. Med. Rehabil. Clin. N. Am. 2008;19:399–418).

Psychosocial factors that can affect child and adolescent athletes before and after an injury include athletic identity, body image, and life stressors, such as a parent's divorce. A stressful situation can increase the risk of sustaining an injury when, for example, it interferes with attention.

The authors cite several studies of different types of young athletes that have found an association between stressful life events and increased risk of sustaining injuries. Stress and coping resources, in addition to the stress of an injury, also can affect athletes after an injury.

As an example, the authors described a 14-year-old basketball player who sustained a severe ankle sprain after the divorce of his parents and missed out on a full season. He became alienated from the team, which had provided support during the divorce. Because his only coping skills were connected to sports, he gave up on physical rehabilitation, and started to experiment with alcohol, marijuana, and sex. But a sports psychology counselor helped the athlete resume involvement in athletics and other activities that helped him improve his behavior and self-esteem.

The damage an injury can do to a young athlete's self-esteem also can increase their risk for a mood disturbance, particularly if the athlete strongly identifies with a sport, according to the authors.

Dr. Nippert and Dr. Smith also cite data suggesting that mood disturbances start immediately after the injury and begin to ebb as athletes feel they are recovering.

However, mood might not return to baseline in some athletes, the authors pointed out, adding, “mood disturbance is a concern for adolescents and young adults who are already at approximately three times greater risk for suicide than the general population.”

When evaluating a young athlete with an injury, medical professionals should be aware of their psychological responses after the injury and during rehabilitation, they advised, noting that “changes in affect, energy, sleep patterns, eye contact, commitment to rehabilitation, and hygiene may be flags for concern.”

They also recommend looking out for signs of an eating disorder, which can affect male and female athletes after an injury, and the use of performance enhancing substances.

Sports injuries among children and adolescents can be very stressful–even if they are minor–but treatment often focuses only on the physical aspects of the injury, not the stress associated with the injury and the recovery period.

If not recognized or addressed, this stress can affect recovery and performance when the individual resumes full participation in the sport, the authors observed.

Psychological interventions that can help athletes cope with psychosocial stressors and improve mood include setting short, intermediate, and long-term goals for rehabilitation and for returning to sports, such as daily goals of icing the injury, elevating the injured area, and managing pain, the authors recommended.

Other interventions that have been reported to help during recovery from a sports injury are the use of relaxation and mental imagery.

“Through awareness and appropriate interventions, medical professionals can help facilitate an optimal physical and physiologic recovery” in young athletes who have sustained a sports injury, Dr. Nippert and Dr. Smith concluded.

The notice is available at www.fda.gov/cdrh/safety/071408-ctscanning.htmlwww.fda.gov/MedWatch/report.htm

The Food and Drug Administration is alerting health care professionals about reports of malfunctions in pacemakers and other electronic medical devices worn by patients during computed tomography scanning.

The agency has received a “small number” of adverse event reports “in which CT scans may have interfered with electronic medical devices, including pacemakers, defibrillators, neurostimulators, and implanted or externally worn drug infusion pumps,” according to a public health notification issued by the FDA.

The adverse events that were likely caused by CT scans were unintended “shocks” (such as stimuli) from neurostimulators, malfunctions of insulin infusion pumps, and transient changes in the output pulse rate of pacemakers.

To date, no deaths have been reported.

These malfunctions can result from direct exposure of the medical device to the high radiation dose rates generated by some CT equipment and are different from the malfunctions related to magnetic resonance imaging, which are caused by strong electric and magnetic fields, the alert says.

The FDA has not received any reports of CT interference with cochlear implants or retinal implants, but says such interference is “theoretically possible.” Problems that “might” be caused by CT scanner interference include resetting or reprogramming of devices and generation of spurious signals, including cardiac defibrillation pulses.

The alert recommends moving external devices out of the range of the scan, if possible, and asking patients with neurostimulators to shut off the device during a scan.

When a CT procedure requires scanning over the device continuously for more than a few seconds, such as during an interventional exam, “attending staff should be ready to take emergency measures to treat adverse reactions if they occur,” the alert emphasized.

Patients should be advised to check their devices for function even if they turned them off during the procedure, and to contact their health care providers if they suspect malfunctioning of their device.

The increase in these reports may be related to greater use of CT scans, the higher dose capability of new CT machines, the larger number of patients wearing devices, and improvements in reporting, according to the FDA, which is continuing to investigate this issue.

The notice is available at www.fda.gov/cdrh/safety/071408-ctscanning.htmlwww.fda.gov/MedWatch/report.htm

The Food and Drug Administration is alerting health care professionals about reports of malfunctions in pacemakers and other electronic medical devices worn by patients during computed tomography scanning.

The agency has received a “small number” of adverse event reports “in which CT scans may have interfered with electronic medical devices, including pacemakers, defibrillators, neurostimulators, and implanted or externally worn drug infusion pumps,” according to a public health notification issued by the FDA.

The adverse events that were likely caused by CT scans were unintended “shocks” (such as stimuli) from neurostimulators, malfunctions of insulin infusion pumps, and transient changes in the output pulse rate of pacemakers.

To date, no deaths have been reported.

These malfunctions can result from direct exposure of the medical device to the high radiation dose rates generated by some CT equipment and are different from the malfunctions related to magnetic resonance imaging, which are caused by strong electric and magnetic fields, the alert says.

The FDA has not received any reports of CT interference with cochlear implants or retinal implants, but says such interference is “theoretically possible.” Problems that “might” be caused by CT scanner interference include resetting or reprogramming of devices and generation of spurious signals, including cardiac defibrillation pulses.

The alert recommends moving external devices out of the range of the scan, if possible, and asking patients with neurostimulators to shut off the device during a scan.

When a CT procedure requires scanning over the device continuously for more than a few seconds, such as during an interventional exam, “attending staff should be ready to take emergency measures to treat adverse reactions if they occur,” the alert emphasized.

Patients should be advised to check their devices for function even if they turned them off during the procedure, and to contact their health care providers if they suspect malfunctioning of their device.

The increase in these reports may be related to greater use of CT scans, the higher dose capability of new CT machines, the larger number of patients wearing devices, and improvements in reporting, according to the FDA, which is continuing to investigate this issue.

The notice is available at www.fda.gov/cdrh/safety/071408-ctscanning.htmlwww.fda.gov/MedWatch/report.htm

The Food and Drug Administration is alerting health care professionals about reports of malfunctions in pacemakers and other electronic medical devices worn by patients during computed tomography scanning.

The agency has received a “small number” of adverse event reports “in which CT scans may have interfered with electronic medical devices, including pacemakers, defibrillators, neurostimulators, and implanted or externally worn drug infusion pumps,” according to a public health notification issued by the FDA.

The adverse events that were likely caused by CT scans were unintended “shocks” (such as stimuli) from neurostimulators, malfunctions of insulin infusion pumps, and transient changes in the output pulse rate of pacemakers.

To date, no deaths have been reported.

These malfunctions can result from direct exposure of the medical device to the high radiation dose rates generated by some CT equipment and are different from the malfunctions related to magnetic resonance imaging, which are caused by strong electric and magnetic fields, the alert says.

The FDA has not received any reports of CT interference with cochlear implants or retinal implants, but says such interference is “theoretically possible.” Problems that “might” be caused by CT scanner interference include resetting or reprogramming of devices and generation of spurious signals, including cardiac defibrillation pulses.

The alert recommends moving external devices out of the range of the scan, if possible, and asking patients with neurostimulators to shut off the device during a scan.

When a CT procedure requires scanning over the device continuously for more than a few seconds, such as during an interventional exam, “attending staff should be ready to take emergency measures to treat adverse reactions if they occur,” the alert emphasized.

Patients should be advised to check their devices for function even if they turned them off during the procedure, and to contact their health care providers if they suspect malfunctioning of their device.

The increase in these reports may be related to greater use of CT scans, the higher dose capability of new CT machines, the larger number of patients wearing devices, and improvements in reporting, according to the FDA, which is continuing to investigate this issue.

The Food and Drug Administration's approval of aripiprazole for the acute treatment of bipolar I disorder in children and adolescents is helpful for physicians and parents, according to an investigator in the study that led to the approval.

The agency approved the atypical antipsychotic aripiprazole (Abilify) for the treatment of manic and mixed episodes associated with bipolar I disorder in children and adolescents.

“When parents have questions now, they can look to the indication and the labeling to know what the common side effects are, how long it takes for the medicine to work, and what they can expect,” Dr. Adelaide Robb, medical director of inpatient psychiatry at Children's National Medical Center, Washington, said in an interview.

The 4-week, multicenter U.S. study compared two fixed doses of aripiprazole to placebo in 296 outpatients, aged 10–17 years, who met DSM-IV criteria for bipolar I disorder manic or mixed episodes with or without psychotic features, and who had a Young Mania Rating Scale (YMRS) score of 20 or more at baseline.

After 4 weeks, improvements from baseline in the mean YMRS total score were significantly greater in patients titrated to a target dose of 10 mg or 30 mg, compared with those on placebo.

Both doses were effective in reducing manic symptoms, compared with placebo, as early as 1 week after treatment started, Dr. Robb said.

Aripiprazole, which was first approved for schizophrenia in 2002, is marketed by Bristol-Myers Squibb Co. and is manufactured by the Otsuka Pharmaceutical Co.

“What is exciting is that this is another labeled indication for pediatric bipolar disorder for ages 10 and up,” said Dr. Robb, who is a speaker for BMS and a consultant to Otsuka.

In the antipsychotic category, the only other drug approved for a pediatric bipolar indication is risperidone (Risperdal), and lithium is in the nonantipsychotic category, she pointed out. Neither divalproex sodium (Depakote) nor oxcarbazepine (Trileptal)—both anticonvulsants that have been approved for bipolar disorder in adults—has been approved for pediatric bipolar treatment because of negative trials, she added.

Risperidone was approved in August 2007 for the short-term treatment of bipolar mania associated with manic or mixed episodes of bipolar I disorder in children and adolescents aged 10–17 years. (It was also approved for treating schizophrenia in adolescents aged 13–17 years at that time.)

Olanzapine (Zyprexa) remains under review at the agency for the treatment of schizophrenia and bipolar disorder in adolescents aged 13–17 years, and the drug is considered “approvable” for those two indications.

In the 4-week aripiprazole study, the most common adverse effects that were observed in at least 5% of those who were in the two aripiprazole-treated groups combined and that were at least twice the rate observed in those on placebo were somnolence (23% vs. 3%), extrapyramidal disorder (20% vs. 3%), fatigue (11% vs. 4%), nausea (11% vs. 4%), akathisia (10% vs. 2%), blurred vision (8% vs. 0%), salivary hypersecretion (6% vs. 0%), and dizziness (5% vs. 1%).

Four of these side effects—extrapyramidal disorder, somnolence, akathisia, and salivary hypersecretion—were possibly related to the dose, as they were more common after 4 weeks of treatment among those on the 30-mg dose and were lowest among those on placebo, according to BMS and Otsuka.

Over the 4 weeks, 9.4% of those on the 30-mg dose gained at least 7% of their baseline weight, compared with 3.2% of those on the 10-mg dose and 3.3% of those on placebo.

Dr. Robb said that now that aripiprazole is approved for bipolar disorder and schizophrenia, a lot more safety data are available than when it was used off label for pediatric patients, based on experience in adults.

The pediatric bipolar indication does not include maintenance treatment. However, Dr. Robb said that the maintenance phase of the treatment trial has been completed, which showed that people continued to experience resolution of manic symptoms.

Dr. Robb said that the reauthorization of the Best Pharmaceuticals for Children Act by Congress will allow the continued expansion of knowledge about medications used in children and adolescents for psychiatric reasons.

Without this legislation—which provides incentives to pharmaceutical companies to study drugs in children and adolescents—these trials would not have been conducted, and providers would still be using adult experience to guide treatment in pediatric patients, Dr. Robb said.

The Food and Drug Administration's approval of aripiprazole for the acute treatment of bipolar I disorder in children and adolescents is helpful for physicians and parents, according to an investigator in the study that led to the approval.

The agency approved the atypical antipsychotic aripiprazole (Abilify) for the treatment of manic and mixed episodes associated with bipolar I disorder in children and adolescents.

“When parents have questions now, they can look to the indication and the labeling to know what the common side effects are, how long it takes for the medicine to work, and what they can expect,” Dr. Adelaide Robb, medical director of inpatient psychiatry at Children's National Medical Center, Washington, said in an interview.

The 4-week, multicenter U.S. study compared two fixed doses of aripiprazole to placebo in 296 outpatients, aged 10–17 years, who met DSM-IV criteria for bipolar I disorder manic or mixed episodes with or without psychotic features, and who had a Young Mania Rating Scale (YMRS) score of 20 or more at baseline.

After 4 weeks, improvements from baseline in the mean YMRS total score were significantly greater in patients titrated to a target dose of 10 mg or 30 mg, compared with those on placebo.

Both doses were effective in reducing manic symptoms, compared with placebo, as early as 1 week after treatment started, Dr. Robb said.

Aripiprazole, which was first approved for schizophrenia in 2002, is marketed by Bristol-Myers Squibb Co. and is manufactured by the Otsuka Pharmaceutical Co.

“What is exciting is that this is another labeled indication for pediatric bipolar disorder for ages 10 and up,” said Dr. Robb, who is a speaker for BMS and a consultant to Otsuka.

In the antipsychotic category, the only other drug approved for a pediatric bipolar indication is risperidone (Risperdal), and lithium is in the nonantipsychotic category, she pointed out. Neither divalproex sodium (Depakote) nor oxcarbazepine (Trileptal)—both anticonvulsants that have been approved for bipolar disorder in adults—has been approved for pediatric bipolar treatment because of negative trials, she added.

Risperidone was approved in August 2007 for the short-term treatment of bipolar mania associated with manic or mixed episodes of bipolar I disorder in children and adolescents aged 10–17 years. (It was also approved for treating schizophrenia in adolescents aged 13–17 years at that time.)

Olanzapine (Zyprexa) remains under review at the agency for the treatment of schizophrenia and bipolar disorder in adolescents aged 13–17 years, and the drug is considered “approvable” for those two indications.

In the 4-week aripiprazole study, the most common adverse effects that were observed in at least 5% of those who were in the two aripiprazole-treated groups combined and that were at least twice the rate observed in those on placebo were somnolence (23% vs. 3%), extrapyramidal disorder (20% vs. 3%), fatigue (11% vs. 4%), nausea (11% vs. 4%), akathisia (10% vs. 2%), blurred vision (8% vs. 0%), salivary hypersecretion (6% vs. 0%), and dizziness (5% vs. 1%).

Four of these side effects—extrapyramidal disorder, somnolence, akathisia, and salivary hypersecretion—were possibly related to the dose, as they were more common after 4 weeks of treatment among those on the 30-mg dose and were lowest among those on placebo, according to BMS and Otsuka.

Over the 4 weeks, 9.4% of those on the 30-mg dose gained at least 7% of their baseline weight, compared with 3.2% of those on the 10-mg dose and 3.3% of those on placebo.

Dr. Robb said that now that aripiprazole is approved for bipolar disorder and schizophrenia, a lot more safety data are available than when it was used off label for pediatric patients, based on experience in adults.

The pediatric bipolar indication does not include maintenance treatment. However, Dr. Robb said that the maintenance phase of the treatment trial has been completed, which showed that people continued to experience resolution of manic symptoms.

Dr. Robb said that the reauthorization of the Best Pharmaceuticals for Children Act by Congress will allow the continued expansion of knowledge about medications used in children and adolescents for psychiatric reasons.

Without this legislation—which provides incentives to pharmaceutical companies to study drugs in children and adolescents—these trials would not have been conducted, and providers would still be using adult experience to guide treatment in pediatric patients, Dr. Robb said.

The Food and Drug Administration's approval of aripiprazole for the acute treatment of bipolar I disorder in children and adolescents is helpful for physicians and parents, according to an investigator in the study that led to the approval.

The agency approved the atypical antipsychotic aripiprazole (Abilify) for the treatment of manic and mixed episodes associated with bipolar I disorder in children and adolescents.

“When parents have questions now, they can look to the indication and the labeling to know what the common side effects are, how long it takes for the medicine to work, and what they can expect,” Dr. Adelaide Robb, medical director of inpatient psychiatry at Children's National Medical Center, Washington, said in an interview.

The 4-week, multicenter U.S. study compared two fixed doses of aripiprazole to placebo in 296 outpatients, aged 10–17 years, who met DSM-IV criteria for bipolar I disorder manic or mixed episodes with or without psychotic features, and who had a Young Mania Rating Scale (YMRS) score of 20 or more at baseline.

After 4 weeks, improvements from baseline in the mean YMRS total score were significantly greater in patients titrated to a target dose of 10 mg or 30 mg, compared with those on placebo.

Both doses were effective in reducing manic symptoms, compared with placebo, as early as 1 week after treatment started, Dr. Robb said.

Aripiprazole, which was first approved for schizophrenia in 2002, is marketed by Bristol-Myers Squibb Co. and is manufactured by the Otsuka Pharmaceutical Co.

“What is exciting is that this is another labeled indication for pediatric bipolar disorder for ages 10 and up,” said Dr. Robb, who is a speaker for BMS and a consultant to Otsuka.

In the antipsychotic category, the only other drug approved for a pediatric bipolar indication is risperidone (Risperdal), and lithium is in the nonantipsychotic category, she pointed out. Neither divalproex sodium (Depakote) nor oxcarbazepine (Trileptal)—both anticonvulsants that have been approved for bipolar disorder in adults—has been approved for pediatric bipolar treatment because of negative trials, she added.

Risperidone was approved in August 2007 for the short-term treatment of bipolar mania associated with manic or mixed episodes of bipolar I disorder in children and adolescents aged 10–17 years. (It was also approved for treating schizophrenia in adolescents aged 13–17 years at that time.)

Olanzapine (Zyprexa) remains under review at the agency for the treatment of schizophrenia and bipolar disorder in adolescents aged 13–17 years, and the drug is considered “approvable” for those two indications.

In the 4-week aripiprazole study, the most common adverse effects that were observed in at least 5% of those who were in the two aripiprazole-treated groups combined and that were at least twice the rate observed in those on placebo were somnolence (23% vs. 3%), extrapyramidal disorder (20% vs. 3%), fatigue (11% vs. 4%), nausea (11% vs. 4%), akathisia (10% vs. 2%), blurred vision (8% vs. 0%), salivary hypersecretion (6% vs. 0%), and dizziness (5% vs. 1%).

Four of these side effects—extrapyramidal disorder, somnolence, akathisia, and salivary hypersecretion—were possibly related to the dose, as they were more common after 4 weeks of treatment among those on the 30-mg dose and were lowest among those on placebo, according to BMS and Otsuka.

Over the 4 weeks, 9.4% of those on the 30-mg dose gained at least 7% of their baseline weight, compared with 3.2% of those on the 10-mg dose and 3.3% of those on placebo.

Dr. Robb said that now that aripiprazole is approved for bipolar disorder and schizophrenia, a lot more safety data are available than when it was used off label for pediatric patients, based on experience in adults.

The pediatric bipolar indication does not include maintenance treatment. However, Dr. Robb said that the maintenance phase of the treatment trial has been completed, which showed that people continued to experience resolution of manic symptoms.

Dr. Robb said that the reauthorization of the Best Pharmaceuticals for Children Act by Congress will allow the continued expansion of knowledge about medications used in children and adolescents for psychiatric reasons.

Without this legislation—which provides incentives to pharmaceutical companies to study drugs in children and adolescents—these trials would not have been conducted, and providers would still be using adult experience to guide treatment in pediatric patients, Dr. Robb said.