Woman loses both legs after salpingectomy: $64.3M award
Due to an ectopic pregnancy, a 29-year-old woman underwent laparoscopic salpingectomy in October 2009. A resident supervised by Dr. A (gynecologist) performed the surgery. Although the patient reported abdominal pain and was febrile, Dr. B (gynecologist) discharged her on postsurgical day 2.

The next day, she returned to the emergency department (ED) with abdominal swelling and pain. Dr. C (ED physician), Dr. D (gynecologist), and Dr. E (general surgeon) examined her. Dr. D began conservative treatment for bowel obstruction. Two days later she was in septic shock. Dr. E repaired a 5-mm injury to the sigmoid colon and created a colostomy. The patient was placed in a medically induced coma for 3 weeks. She experienced cardiac arrest 3 times during her 73-day ICU stay. She  underwent skin grafts, and suffered hearing loss as a result of antibiotic treatment. Due to gangrene, both legs were amputated below the knee.

At the trial’s conclusion in January 2014, the colostomy had not been reversed. She has difficulty caring for her daughter and has not worked since the initial operation.

PATIENT’S CLAIM The resident, who injured the colon and did not detect the injury during surgery, was improperly supervised by Dr. A. Hospital staff did not communicate the patient’s problem reports to the physicians. Dr. B should not have discharged her after surgery; based on her reported symptoms, additional testing was warranted. Drs. C, D, and E did not react to the patient’s pain reports in a timely manner, nor treat the resulting sepsis aggressively enough, leading to gangrene.

DEFENDANTS’ DEFENSE The patient’s colon injury was diagnosed and treated in a timely manner, but her condition deteriorated rapidly. The physicians acted responsibly based on the available information; a computed tomography scan did not show the colon injury. The injury likely occurred after the procedure due to an underlying bowel condition and is a known risk of the procedure. The colostomy can be reversed. Their efforts saved her life.

VERDICT The patient and Dr. E negotiated a $2.3 million settlement. A $62 million New York verdict was returned. The jury found the hospital 40% liable; Dr. A 30% liable; Dr. B 20% liable; and Dr. D 10% liable. Claims were dropped against the resident and Dr. C.

Related article: Oophorectomy or salpingectomy—which makes more sense? William H. Parker, MD (March 2014)

PARENTS REQUESTED EARLIER CESAREAN: CHILD HAS CP
A woman was in labor for 2 full days before her ObGyn performed a cesarean delivery. The child was born with abnormal Apgar scores and had seizures. Imaging studies revealed brain damage. She received a diagnosis of cerebral palsy.

PARENTS’ CLAIM The parents first requested cesarean delivery early on the second day, but the ObGyn allowed labor to progress. When the fetal heart-rate monitor showed signs of fetal distress 3 hours later, the parents made a second request; the ObGyn continued with vaginal delivery. The child was ultimately born by cesarean delivery. Her brain damage was caused by lack of oxygen from failure to perform an earlier cesarean delivery.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4.25 million Massachusetts settlement was reached.

BLADDER INJURED DURING CESAREAN DELIVERY
A 33-year-old woman gave birth via cesarean delivery performed by her ObGyn. During the procedure, the patient’s bladder was lacerated and the injury was immediately repaired. The patient reports occasional urinary incontinence and pain.

PATIENT’S CLAIM The ObGyn should have anticipated that the bladder would be shifted because of the patient’s previous cesarean delivery.

PHYSICIAN’S DEFENSE The injury is a known risk of the procedure. The patient had developed adhesions that caused the bladder to become displaced. She does not suffer permanent residual effects from the injury.

VERDICT A $125,000 New York verdict was returned.

Related article: 10 practical, evidence-based recommendations for improving maternal outcomes of cesarean delivery. Baha M. Sibai (March 2012)

PARENTS REQUESTED SPECIFIC GENETIC TESTING, BUT CHILD IS BORN WITH RARE CHROMOSOMAL CONDITION: $50M VERDICT
Parents sought prenatal genetic testing to determine if their fetus had a specific genetic condition because the father carries a rare chromosomal abnormality called an unbalanced chromosome translocation. This defect can only be identified if the laboratory is told precisely where to look for the specific translocation; it is not detected on routine prenatal genetic testing. After testing, the parents were told that the fetus did not have the chromosomal abnormality.

The child was born with the condition for which testing was sought, resulting in severe physical and cognitive impairments and multiple physical abnormalities. He will require 24-hour care for life.

PARENTS’ CLAIM Testing failed to identify the condition; the couple had decided to terminate the pregnancy if the child was affected. Due to budget cuts in the maternal-fetal medicine clinic, the medical center borrowed a genetic counselor from another hospital one day a week. The parents told the genetic counselor of the family’s history of the defect and explained that the laboratory’s procedures require the referring center to obtain and share the necessary detailed information with the lab. The lab was apparently notified that the couple had a family history of the defect, but the genetic counselor did not transmit specific information to the lab, and lab personnel did not appropriately follow-up.

DEFENDANTS’ DEFENSE The medical center blamed the laboratory: the lab’s standard procedures state that the lab should call the referring center to obtain the necessary detailed information if it was not provided; the lab employee who handled the specimen did not do so. The lab claimed that the genetic counselor did not transmit the specific information to the lab.

The laboratory disputed the child’s need for 24/7 care, maintaining that he could live in a group home with only occasional nursing care.

VERDICT A $50 million Washington verdict was returned against the medical center and laboratory; each defendant will pay $25 million.

Related article: Noninvasive prenatal testing: Where we are and where we’re going. Lee P. Shulman, MD (Commentary; May 2014)

NECROTIZING FASCIITIS AFTER SURGERY
A 57-year-old woman underwent surgery to repair vaginal vault prolapse, rectocele, and enterocele, performed by her gynecologist. Several days after discharge, the patient returned to the hospital with an infection in her leg that had evolved into necrotizing fasciitis. She underwent five fasciotomies and was hospitalized for 3 weeks.

PATIENT’S CLAIM The gynecologist should have administered prophylactic antibiotics before, during, and after surgery. The patient has massive scarring of her leg.

PHYSICIAN’S DEFENSE The infection was not a result of failing to administer antibiotics. The patient failed to seek timely treatment of symptoms that developed after surgery.

VERDICT A $400,000 New York verdict was returned but reduced because the jury found the patient 49% at fault.

OXYTOCIN BLAMED FOR CHILD’S CP
A mother had bariatric surgery 12 months before becoming pregnant, and she smoked during pregnancy. She developed placental insufficiency and labor was induced shortly after she reached 37 weeks’ gestation.

During delivery, the mother was given oxytocin to increase the frequency and strength of contractions. Nurses repeatedly stopped the oxytocin in response to decelerations in the fetal heart rate, but physicians ordered the oxytocin resumed, even after fetal heart-rate monitoring showed fetal distress.

Three days after birth, the child was transferred to another hospital, and was found to have cerebral palsy and other injuries. At age 5, the child is nonverbal, cannot walk, and requires a feeding tube.

PARENTS’ CLAIM Oxytocin should have been stopped and a cesarean delivery performed when fetal distress was first noted.

DEFENDANTS’ DEFENSE There was no need for cesarean delivery. Apgar scores, blood gases, and fetal presentation indicated that the injury occurred prior to labor.

VERDICT A $6 million Texas settlement was reached during the trial.

Related article: Q: Following cesarean delivery, what is the optimal oxytocin infusion duration to prevent postpartum bleeding? Robert L. Barbieri, MD (Editorial; April 2014)

MOTHER DISCHARGED DESPITE SEVERE ABDOMINAL PAIN
A woman had prenatal care at different locations. Her history included two cesarean deliveries.

Reporting severe abdominal pain, she was taken from a homeless shelter to an ED by ambulance. The mother was uncertain of the fetus’ gestational age; a 4th-year obstetric resident determined by physical examination that the pregnancy was at 36.5 weeks. The resident discussed the case with the attending ObGyn, who said to discharge the mother if her pain was gone. After 11 hours, the mother was returned to the shelter.

The mother returned to the ED 12 hours later. Thirty-five minutes after fetal distress was identified, an emergency cesarean delivery was performed. At birth, the child was found to be at 38 to 39 weeks’ gestation. He received a diagnosis of severe hypoxic ischemic encephalopathy and was transferred to a children’s hospital for brain cooling.

The child lives in a long-term care facility and is dependent on a ventilator and gastronomy tube.

PARENT’S CLAIM The mother should not have been discharged after the first visit. A cesarean delivery should have been performed at that time. The attending ObGyn never saw the mother.

DEFENDANTS’ DEFENSE The mother should have given her correct due date, which was in her prenatal records based on previous ultrasonograpy. The first discharge was proper, as the pain had improved. The homeless shelter should have called an ambulance earlier for the second admission.

VERDICT A $7.5 million California settlement was reached, plus payment of medical expenses exceeding $300,000. 

Timing of child’s injury disputed
Vaginal birth after cesarean (VBAC) had been planned. After reporting to her ObGyn that she was in labor, a mother went to the ED.

During the next few hours, hospital staff called the ObGyn twice to report that fetal monitor strips indicated tachycardia. The ObGyn then spoke to the mother by phone and told her that cesarean delivery was necessary but could wait for him to get to the hospital. After the ObGyn arrived, he removed the fetal heart-rate monitor to prepare the mother’s abdomen; cesarean delivery occurred 15 minutes later.

The child has spastic dystonic quadriplegia and requires 24-hour care.

PARENT’S CLAIM The ObGyn should have come to the hospital and performed cesarean delivery when he was first notified that the fetus was tachycardic. The baby suffered an hypoxic ischemic event in the 15-minute period between when the monitor was removed and birth, causing hypoxic ischemic encephalopathy.

PHYSICIAN’S DEFENSE There was no indication of a need for earlier delivery. The brain injury occurred prior to labor and delivery.

VERDICT The hospital settled for a confidential amount before the trial. An Illinois defense verdict was returned for the ObGyn.

Were mammograms properly interpreted?
After reporting a lump in her breast, a 39-year-old woman underwent mammography in 2008 and 2009. Two different radiologists reported their findings as negative for cancer.

In 2010, the patient was found to have breast cancer. She underwent a mastectomy, chemotherapy, and radiation therapy, and was given a 75%–80% chance of 5-year survival.

PATIENT’S CLAIM The ObGyn failed to follow-up on the patient’s reports of a breast lump. The radiologists did not correctly interpret the 2008 and 2009 mammograms. If cancer had been detected earlier, treatment would have been less extreme.

PHYSICIANS’ DEFENSE The ObGyn claimed that he would have felt a lump if it was present. The first radiologist claimed that the 2008 mammography report was correct, noting that the patient’s cancer was a lobular carcinoma that does not always show on mammography or in patients with dense breasts, which this patient has. 

VERDICT A directed verdict was granted to the radiologist who interpreted the 2009 mammography, as the results were lost. An Ohio defense verdict was returned for the ObGyn and the other radiologist.

Related article: Does screening mammography save lives? Janelle Yates, Senior Editor (April 2014)

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

TELL US WHAT YOU THINK! Drop us a line and let us know what you think about this or other current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice.
Tell us what you think by emailing us at: [email protected] Please include your name, city and state.
Stay in touch! Your feedback is important to us!

Woman loses both legs after salpingectomy: $64.3M award
Due to an ectopic pregnancy, a 29-year-old woman underwent laparoscopic salpingectomy in October 2009. A resident supervised by Dr. A (gynecologist) performed the surgery. Although the patient reported abdominal pain and was febrile, Dr. B (gynecologist) discharged her on postsurgical day 2.

The next day, she returned to the emergency department (ED) with abdominal swelling and pain. Dr. C (ED physician), Dr. D (gynecologist), and Dr. E (general surgeon) examined her. Dr. D began conservative treatment for bowel obstruction. Two days later she was in septic shock. Dr. E repaired a 5-mm injury to the sigmoid colon and created a colostomy. The patient was placed in a medically induced coma for 3 weeks. She experienced cardiac arrest 3 times during her 73-day ICU stay. She  underwent skin grafts, and suffered hearing loss as a result of antibiotic treatment. Due to gangrene, both legs were amputated below the knee.

At the trial’s conclusion in January 2014, the colostomy had not been reversed. She has difficulty caring for her daughter and has not worked since the initial operation.

PATIENT’S CLAIM The resident, who injured the colon and did not detect the injury during surgery, was improperly supervised by Dr. A. Hospital staff did not communicate the patient’s problem reports to the physicians. Dr. B should not have discharged her after surgery; based on her reported symptoms, additional testing was warranted. Drs. C, D, and E did not react to the patient’s pain reports in a timely manner, nor treat the resulting sepsis aggressively enough, leading to gangrene.

DEFENDANTS’ DEFENSE The patient’s colon injury was diagnosed and treated in a timely manner, but her condition deteriorated rapidly. The physicians acted responsibly based on the available information; a computed tomography scan did not show the colon injury. The injury likely occurred after the procedure due to an underlying bowel condition and is a known risk of the procedure. The colostomy can be reversed. Their efforts saved her life.

VERDICT The patient and Dr. E negotiated a $2.3 million settlement. A $62 million New York verdict was returned. The jury found the hospital 40% liable; Dr. A 30% liable; Dr. B 20% liable; and Dr. D 10% liable. Claims were dropped against the resident and Dr. C.

Related article: Oophorectomy or salpingectomy—which makes more sense? William H. Parker, MD (March 2014)

PARENTS REQUESTED EARLIER CESAREAN: CHILD HAS CP
A woman was in labor for 2 full days before her ObGyn performed a cesarean delivery. The child was born with abnormal Apgar scores and had seizures. Imaging studies revealed brain damage. She received a diagnosis of cerebral palsy.

PARENTS’ CLAIM The parents first requested cesarean delivery early on the second day, but the ObGyn allowed labor to progress. When the fetal heart-rate monitor showed signs of fetal distress 3 hours later, the parents made a second request; the ObGyn continued with vaginal delivery. The child was ultimately born by cesarean delivery. Her brain damage was caused by lack of oxygen from failure to perform an earlier cesarean delivery.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4.25 million Massachusetts settlement was reached.

BLADDER INJURED DURING CESAREAN DELIVERY
A 33-year-old woman gave birth via cesarean delivery performed by her ObGyn. During the procedure, the patient’s bladder was lacerated and the injury was immediately repaired. The patient reports occasional urinary incontinence and pain.

PATIENT’S CLAIM The ObGyn should have anticipated that the bladder would be shifted because of the patient’s previous cesarean delivery.

PHYSICIAN’S DEFENSE The injury is a known risk of the procedure. The patient had developed adhesions that caused the bladder to become displaced. She does not suffer permanent residual effects from the injury.

VERDICT A $125,000 New York verdict was returned.

Related article: 10 practical, evidence-based recommendations for improving maternal outcomes of cesarean delivery. Baha M. Sibai (March 2012)

PARENTS REQUESTED SPECIFIC GENETIC TESTING, BUT CHILD IS BORN WITH RARE CHROMOSOMAL CONDITION: $50M VERDICT
Parents sought prenatal genetic testing to determine if their fetus had a specific genetic condition because the father carries a rare chromosomal abnormality called an unbalanced chromosome translocation. This defect can only be identified if the laboratory is told precisely where to look for the specific translocation; it is not detected on routine prenatal genetic testing. After testing, the parents were told that the fetus did not have the chromosomal abnormality.

The child was born with the condition for which testing was sought, resulting in severe physical and cognitive impairments and multiple physical abnormalities. He will require 24-hour care for life.

PARENTS’ CLAIM Testing failed to identify the condition; the couple had decided to terminate the pregnancy if the child was affected. Due to budget cuts in the maternal-fetal medicine clinic, the medical center borrowed a genetic counselor from another hospital one day a week. The parents told the genetic counselor of the family’s history of the defect and explained that the laboratory’s procedures require the referring center to obtain and share the necessary detailed information with the lab. The lab was apparently notified that the couple had a family history of the defect, but the genetic counselor did not transmit specific information to the lab, and lab personnel did not appropriately follow-up.

DEFENDANTS’ DEFENSE The medical center blamed the laboratory: the lab’s standard procedures state that the lab should call the referring center to obtain the necessary detailed information if it was not provided; the lab employee who handled the specimen did not do so. The lab claimed that the genetic counselor did not transmit the specific information to the lab.

The laboratory disputed the child’s need for 24/7 care, maintaining that he could live in a group home with only occasional nursing care.

VERDICT A $50 million Washington verdict was returned against the medical center and laboratory; each defendant will pay $25 million.

Related article: Noninvasive prenatal testing: Where we are and where we’re going. Lee P. Shulman, MD (Commentary; May 2014)

NECROTIZING FASCIITIS AFTER SURGERY
A 57-year-old woman underwent surgery to repair vaginal vault prolapse, rectocele, and enterocele, performed by her gynecologist. Several days after discharge, the patient returned to the hospital with an infection in her leg that had evolved into necrotizing fasciitis. She underwent five fasciotomies and was hospitalized for 3 weeks.

PATIENT’S CLAIM The gynecologist should have administered prophylactic antibiotics before, during, and after surgery. The patient has massive scarring of her leg.

PHYSICIAN’S DEFENSE The infection was not a result of failing to administer antibiotics. The patient failed to seek timely treatment of symptoms that developed after surgery.

VERDICT A $400,000 New York verdict was returned but reduced because the jury found the patient 49% at fault.

OXYTOCIN BLAMED FOR CHILD’S CP
A mother had bariatric surgery 12 months before becoming pregnant, and she smoked during pregnancy. She developed placental insufficiency and labor was induced shortly after she reached 37 weeks’ gestation.

During delivery, the mother was given oxytocin to increase the frequency and strength of contractions. Nurses repeatedly stopped the oxytocin in response to decelerations in the fetal heart rate, but physicians ordered the oxytocin resumed, even after fetal heart-rate monitoring showed fetal distress.

Three days after birth, the child was transferred to another hospital, and was found to have cerebral palsy and other injuries. At age 5, the child is nonverbal, cannot walk, and requires a feeding tube.

PARENTS’ CLAIM Oxytocin should have been stopped and a cesarean delivery performed when fetal distress was first noted.

DEFENDANTS’ DEFENSE There was no need for cesarean delivery. Apgar scores, blood gases, and fetal presentation indicated that the injury occurred prior to labor.

VERDICT A $6 million Texas settlement was reached during the trial.

Related article: Q: Following cesarean delivery, what is the optimal oxytocin infusion duration to prevent postpartum bleeding? Robert L. Barbieri, MD (Editorial; April 2014)

MOTHER DISCHARGED DESPITE SEVERE ABDOMINAL PAIN
A woman had prenatal care at different locations. Her history included two cesarean deliveries.

Reporting severe abdominal pain, she was taken from a homeless shelter to an ED by ambulance. The mother was uncertain of the fetus’ gestational age; a 4th-year obstetric resident determined by physical examination that the pregnancy was at 36.5 weeks. The resident discussed the case with the attending ObGyn, who said to discharge the mother if her pain was gone. After 11 hours, the mother was returned to the shelter.

The mother returned to the ED 12 hours later. Thirty-five minutes after fetal distress was identified, an emergency cesarean delivery was performed. At birth, the child was found to be at 38 to 39 weeks’ gestation. He received a diagnosis of severe hypoxic ischemic encephalopathy and was transferred to a children’s hospital for brain cooling.

The child lives in a long-term care facility and is dependent on a ventilator and gastronomy tube.

PARENT’S CLAIM The mother should not have been discharged after the first visit. A cesarean delivery should have been performed at that time. The attending ObGyn never saw the mother.

DEFENDANTS’ DEFENSE The mother should have given her correct due date, which was in her prenatal records based on previous ultrasonograpy. The first discharge was proper, as the pain had improved. The homeless shelter should have called an ambulance earlier for the second admission.

VERDICT A $7.5 million California settlement was reached, plus payment of medical expenses exceeding $300,000. 

Timing of child’s injury disputed
Vaginal birth after cesarean (VBAC) had been planned. After reporting to her ObGyn that she was in labor, a mother went to the ED.

During the next few hours, hospital staff called the ObGyn twice to report that fetal monitor strips indicated tachycardia. The ObGyn then spoke to the mother by phone and told her that cesarean delivery was necessary but could wait for him to get to the hospital. After the ObGyn arrived, he removed the fetal heart-rate monitor to prepare the mother’s abdomen; cesarean delivery occurred 15 minutes later.

The child has spastic dystonic quadriplegia and requires 24-hour care.

PARENT’S CLAIM The ObGyn should have come to the hospital and performed cesarean delivery when he was first notified that the fetus was tachycardic. The baby suffered an hypoxic ischemic event in the 15-minute period between when the monitor was removed and birth, causing hypoxic ischemic encephalopathy.

PHYSICIAN’S DEFENSE There was no indication of a need for earlier delivery. The brain injury occurred prior to labor and delivery.

VERDICT The hospital settled for a confidential amount before the trial. An Illinois defense verdict was returned for the ObGyn.

Were mammograms properly interpreted?
After reporting a lump in her breast, a 39-year-old woman underwent mammography in 2008 and 2009. Two different radiologists reported their findings as negative for cancer.

In 2010, the patient was found to have breast cancer. She underwent a mastectomy, chemotherapy, and radiation therapy, and was given a 75%–80% chance of 5-year survival.

PATIENT’S CLAIM The ObGyn failed to follow-up on the patient’s reports of a breast lump. The radiologists did not correctly interpret the 2008 and 2009 mammograms. If cancer had been detected earlier, treatment would have been less extreme.

PHYSICIANS’ DEFENSE The ObGyn claimed that he would have felt a lump if it was present. The first radiologist claimed that the 2008 mammography report was correct, noting that the patient’s cancer was a lobular carcinoma that does not always show on mammography or in patients with dense breasts, which this patient has. 

VERDICT A directed verdict was granted to the radiologist who interpreted the 2009 mammography, as the results were lost. An Ohio defense verdict was returned for the ObGyn and the other radiologist.

Related article: Does screening mammography save lives? Janelle Yates, Senior Editor (April 2014)

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

TELL US WHAT YOU THINK! Drop us a line and let us know what you think about this or other current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice.
Tell us what you think by emailing us at: [email protected] Please include your name, city and state.
Stay in touch! Your feedback is important to us!

Woman loses both legs after salpingectomy: $64.3M award
Due to an ectopic pregnancy, a 29-year-old woman underwent laparoscopic salpingectomy in October 2009. A resident supervised by Dr. A (gynecologist) performed the surgery. Although the patient reported abdominal pain and was febrile, Dr. B (gynecologist) discharged her on postsurgical day 2.

The next day, she returned to the emergency department (ED) with abdominal swelling and pain. Dr. C (ED physician), Dr. D (gynecologist), and Dr. E (general surgeon) examined her. Dr. D began conservative treatment for bowel obstruction. Two days later she was in septic shock. Dr. E repaired a 5-mm injury to the sigmoid colon and created a colostomy. The patient was placed in a medically induced coma for 3 weeks. She experienced cardiac arrest 3 times during her 73-day ICU stay. She  underwent skin grafts, and suffered hearing loss as a result of antibiotic treatment. Due to gangrene, both legs were amputated below the knee.

At the trial’s conclusion in January 2014, the colostomy had not been reversed. She has difficulty caring for her daughter and has not worked since the initial operation.

PATIENT’S CLAIM The resident, who injured the colon and did not detect the injury during surgery, was improperly supervised by Dr. A. Hospital staff did not communicate the patient’s problem reports to the physicians. Dr. B should not have discharged her after surgery; based on her reported symptoms, additional testing was warranted. Drs. C, D, and E did not react to the patient’s pain reports in a timely manner, nor treat the resulting sepsis aggressively enough, leading to gangrene.

DEFENDANTS’ DEFENSE The patient’s colon injury was diagnosed and treated in a timely manner, but her condition deteriorated rapidly. The physicians acted responsibly based on the available information; a computed tomography scan did not show the colon injury. The injury likely occurred after the procedure due to an underlying bowel condition and is a known risk of the procedure. The colostomy can be reversed. Their efforts saved her life.

VERDICT The patient and Dr. E negotiated a $2.3 million settlement. A $62 million New York verdict was returned. The jury found the hospital 40% liable; Dr. A 30% liable; Dr. B 20% liable; and Dr. D 10% liable. Claims were dropped against the resident and Dr. C.

Related article: Oophorectomy or salpingectomy—which makes more sense? William H. Parker, MD (March 2014)

PARENTS REQUESTED EARLIER CESAREAN: CHILD HAS CP
A woman was in labor for 2 full days before her ObGyn performed a cesarean delivery. The child was born with abnormal Apgar scores and had seizures. Imaging studies revealed brain damage. She received a diagnosis of cerebral palsy.

PARENTS’ CLAIM The parents first requested cesarean delivery early on the second day, but the ObGyn allowed labor to progress. When the fetal heart-rate monitor showed signs of fetal distress 3 hours later, the parents made a second request; the ObGyn continued with vaginal delivery. The child was ultimately born by cesarean delivery. Her brain damage was caused by lack of oxygen from failure to perform an earlier cesarean delivery.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4.25 million Massachusetts settlement was reached.

BLADDER INJURED DURING CESAREAN DELIVERY
A 33-year-old woman gave birth via cesarean delivery performed by her ObGyn. During the procedure, the patient’s bladder was lacerated and the injury was immediately repaired. The patient reports occasional urinary incontinence and pain.

PATIENT’S CLAIM The ObGyn should have anticipated that the bladder would be shifted because of the patient’s previous cesarean delivery.

PHYSICIAN’S DEFENSE The injury is a known risk of the procedure. The patient had developed adhesions that caused the bladder to become displaced. She does not suffer permanent residual effects from the injury.

VERDICT A $125,000 New York verdict was returned.

Related article: 10 practical, evidence-based recommendations for improving maternal outcomes of cesarean delivery. Baha M. Sibai (March 2012)

PARENTS REQUESTED SPECIFIC GENETIC TESTING, BUT CHILD IS BORN WITH RARE CHROMOSOMAL CONDITION: $50M VERDICT
Parents sought prenatal genetic testing to determine if their fetus had a specific genetic condition because the father carries a rare chromosomal abnormality called an unbalanced chromosome translocation. This defect can only be identified if the laboratory is told precisely where to look for the specific translocation; it is not detected on routine prenatal genetic testing. After testing, the parents were told that the fetus did not have the chromosomal abnormality.

The child was born with the condition for which testing was sought, resulting in severe physical and cognitive impairments and multiple physical abnormalities. He will require 24-hour care for life.

PARENTS’ CLAIM Testing failed to identify the condition; the couple had decided to terminate the pregnancy if the child was affected. Due to budget cuts in the maternal-fetal medicine clinic, the medical center borrowed a genetic counselor from another hospital one day a week. The parents told the genetic counselor of the family’s history of the defect and explained that the laboratory’s procedures require the referring center to obtain and share the necessary detailed information with the lab. The lab was apparently notified that the couple had a family history of the defect, but the genetic counselor did not transmit specific information to the lab, and lab personnel did not appropriately follow-up.

DEFENDANTS’ DEFENSE The medical center blamed the laboratory: the lab’s standard procedures state that the lab should call the referring center to obtain the necessary detailed information if it was not provided; the lab employee who handled the specimen did not do so. The lab claimed that the genetic counselor did not transmit the specific information to the lab.

The laboratory disputed the child’s need for 24/7 care, maintaining that he could live in a group home with only occasional nursing care.

VERDICT A $50 million Washington verdict was returned against the medical center and laboratory; each defendant will pay $25 million.

Related article: Noninvasive prenatal testing: Where we are and where we’re going. Lee P. Shulman, MD (Commentary; May 2014)

NECROTIZING FASCIITIS AFTER SURGERY
A 57-year-old woman underwent surgery to repair vaginal vault prolapse, rectocele, and enterocele, performed by her gynecologist. Several days after discharge, the patient returned to the hospital with an infection in her leg that had evolved into necrotizing fasciitis. She underwent five fasciotomies and was hospitalized for 3 weeks.

PATIENT’S CLAIM The gynecologist should have administered prophylactic antibiotics before, during, and after surgery. The patient has massive scarring of her leg.

PHYSICIAN’S DEFENSE The infection was not a result of failing to administer antibiotics. The patient failed to seek timely treatment of symptoms that developed after surgery.

VERDICT A $400,000 New York verdict was returned but reduced because the jury found the patient 49% at fault.

OXYTOCIN BLAMED FOR CHILD’S CP
A mother had bariatric surgery 12 months before becoming pregnant, and she smoked during pregnancy. She developed placental insufficiency and labor was induced shortly after she reached 37 weeks’ gestation.

During delivery, the mother was given oxytocin to increase the frequency and strength of contractions. Nurses repeatedly stopped the oxytocin in response to decelerations in the fetal heart rate, but physicians ordered the oxytocin resumed, even after fetal heart-rate monitoring showed fetal distress.

Three days after birth, the child was transferred to another hospital, and was found to have cerebral palsy and other injuries. At age 5, the child is nonverbal, cannot walk, and requires a feeding tube.

PARENTS’ CLAIM Oxytocin should have been stopped and a cesarean delivery performed when fetal distress was first noted.

DEFENDANTS’ DEFENSE There was no need for cesarean delivery. Apgar scores, blood gases, and fetal presentation indicated that the injury occurred prior to labor.

VERDICT A $6 million Texas settlement was reached during the trial.

Related article: Q: Following cesarean delivery, what is the optimal oxytocin infusion duration to prevent postpartum bleeding? Robert L. Barbieri, MD (Editorial; April 2014)

MOTHER DISCHARGED DESPITE SEVERE ABDOMINAL PAIN
A woman had prenatal care at different locations. Her history included two cesarean deliveries.

Reporting severe abdominal pain, she was taken from a homeless shelter to an ED by ambulance. The mother was uncertain of the fetus’ gestational age; a 4th-year obstetric resident determined by physical examination that the pregnancy was at 36.5 weeks. The resident discussed the case with the attending ObGyn, who said to discharge the mother if her pain was gone. After 11 hours, the mother was returned to the shelter.

The mother returned to the ED 12 hours later. Thirty-five minutes after fetal distress was identified, an emergency cesarean delivery was performed. At birth, the child was found to be at 38 to 39 weeks’ gestation. He received a diagnosis of severe hypoxic ischemic encephalopathy and was transferred to a children’s hospital for brain cooling.

The child lives in a long-term care facility and is dependent on a ventilator and gastronomy tube.

PARENT’S CLAIM The mother should not have been discharged after the first visit. A cesarean delivery should have been performed at that time. The attending ObGyn never saw the mother.

DEFENDANTS’ DEFENSE The mother should have given her correct due date, which was in her prenatal records based on previous ultrasonograpy. The first discharge was proper, as the pain had improved. The homeless shelter should have called an ambulance earlier for the second admission.

VERDICT A $7.5 million California settlement was reached, plus payment of medical expenses exceeding $300,000. 

Timing of child’s injury disputed
Vaginal birth after cesarean (VBAC) had been planned. After reporting to her ObGyn that she was in labor, a mother went to the ED.

During the next few hours, hospital staff called the ObGyn twice to report that fetal monitor strips indicated tachycardia. The ObGyn then spoke to the mother by phone and told her that cesarean delivery was necessary but could wait for him to get to the hospital. After the ObGyn arrived, he removed the fetal heart-rate monitor to prepare the mother’s abdomen; cesarean delivery occurred 15 minutes later.

The child has spastic dystonic quadriplegia and requires 24-hour care.

PARENT’S CLAIM The ObGyn should have come to the hospital and performed cesarean delivery when he was first notified that the fetus was tachycardic. The baby suffered an hypoxic ischemic event in the 15-minute period between when the monitor was removed and birth, causing hypoxic ischemic encephalopathy.

PHYSICIAN’S DEFENSE There was no indication of a need for earlier delivery. The brain injury occurred prior to labor and delivery.

VERDICT The hospital settled for a confidential amount before the trial. An Illinois defense verdict was returned for the ObGyn.

Were mammograms properly interpreted?
After reporting a lump in her breast, a 39-year-old woman underwent mammography in 2008 and 2009. Two different radiologists reported their findings as negative for cancer.

In 2010, the patient was found to have breast cancer. She underwent a mastectomy, chemotherapy, and radiation therapy, and was given a 75%–80% chance of 5-year survival.

PATIENT’S CLAIM The ObGyn failed to follow-up on the patient’s reports of a breast lump. The radiologists did not correctly interpret the 2008 and 2009 mammograms. If cancer had been detected earlier, treatment would have been less extreme.

PHYSICIANS’ DEFENSE The ObGyn claimed that he would have felt a lump if it was present. The first radiologist claimed that the 2008 mammography report was correct, noting that the patient’s cancer was a lobular carcinoma that does not always show on mammography or in patients with dense breasts, which this patient has. 

VERDICT A directed verdict was granted to the radiologist who interpreted the 2009 mammography, as the results were lost. An Ohio defense verdict was returned for the ObGyn and the other radiologist.

Related article: Does screening mammography save lives? Janelle Yates, Senior Editor (April 2014)

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Cancer patient receives therapy

Credit: Rhoda Baer

Results of a large study suggest certain malignanices are more concentrated in areas with high levels of poverty, while other cancer types arise more often in wealthy regions.

The research, conducted using data from nearly 3 million US cancer cases, also indicated that areas with higher poverty levels tended to have a lower cancer incidence but higher mortality rate than areas with lower poverty levels.

Researchers reported these findings in the journal Cancer.

Francis Boscoe, PhD, of the New York State Cancer Registry in Albany, and his colleagues conducted this research to evaluate the role of socioeconomics in cancer incidence and mortality.

So the team compared individuals living in areas with the highest poverty levels to those living in areas with the lowest poverty levels.

The researchers collected information on nearly 3 million cancer cases diagnosed between 2005 and 2009 in16 states, plus Los Angeles (an area covering 42% of the US population). Cases were divided into 1 of 4 groupings based on the poverty rate of the residential census tract at the time of diagnosis.

For all malignancies combined, there was a negligible association between cancer incidence and poverty. However, 32 of 39 cancer types showed a significant association with poverty.

Fourteen cancers were positively associated with poverty, and 18 were negatively associated. Myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma (NHL) were among the negatively associated malignancies.

The cancers most significantly associated with higher poverty levels were Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver. The cancers most significantly associated with lower poverty levels were melanoma, thyroid cancer, other non-epithelial skin cancers, and testis cancer.

Overall, male malignancy rates were more sensitive to poverty level than female rates. And, in general, the race-specific cancer incidence rates differed, but the poverty gradients were similar.

For example, there was a roughly 20-fold difference in rates of melanoma between white and black individuals, but the relationship between poverty and incidence remained regardless of race.

This was not true for NHL, however. Among black individuals, the incidence of NHL increased as the poverty level increased. But among white individuals, the incidence of NHL decreased as the poverty level increased.

The researchers pointed out that—for all cancer sites, races, and sexes combined—the difference in risk between the greatest and lowest poverty category was less than 2%.

“At first glance, the effects seem to cancel one another out,” Dr Boscoe said. “But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality. When it comes to cancer, the poor are more likely to die of the disease, while the affluent are more likely to die with the disease.”

Dr Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance.

“Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future,” he concluded.

Monoclonal antibodies

Credit: Linda Bartlett

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.

The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.

The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.

Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.

Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full

approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.

The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.

The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.

Phase 2 study

Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.

Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.

Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m² for the untreated patients and 70 mg/m² for relapsed patients.

However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m², and the relapsed patients were reduced to 50 mg/m².

The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.

CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.

Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.

This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).

There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of  treatment.

Phase 3 study

Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.

Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.

Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.

In both arms, patients received chlorambucil at a dose of 10 mg/m² orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.

The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.

At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).

Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.

Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.

In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.

Monoclonal antibodies

Credit: Linda Bartlett

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.

The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.

The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.

Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.

Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full

approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.

The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.

The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.

Phase 2 study

Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.

Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.

Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m² for the untreated patients and 70 mg/m² for relapsed patients.

However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m², and the relapsed patients were reduced to 50 mg/m².

The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.

CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.

Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.

This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).

There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of  treatment.

Phase 3 study

Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.

Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.

Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.

In both arms, patients received chlorambucil at a dose of 10 mg/m² orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.

The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.

At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).

Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.

Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.

In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.

Monoclonal antibodies

Credit: Linda Bartlett

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.

The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.

The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.

Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.

Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full

approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.

The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.

The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.

Phase 2 study

Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.

Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.

Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m² for the untreated patients and 70 mg/m² for relapsed patients.

However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m², and the relapsed patients were reduced to 50 mg/m².

The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.

CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.

Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.

This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).

There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of  treatment.

Phase 3 study

Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.

Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.

Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.

In both arms, patients received chlorambucil at a dose of 10 mg/m² orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.

The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.

At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).

Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.

Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.

In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.

At the 2014 National Comprehensive Cancer Network annual conference in Hollywood, Florida, Dr Andrew D Zelenetz, chair of the NCCN Non-Hodgkin Lymphomas Guidelines panel, presented guideline updates for non-Hodgkin lymphomas.

Click on the PDF icon at the top of this introduction to read the full article.

At the 2014 National Comprehensive Cancer Network annual conference in Hollywood, Florida, Dr Andrew D Zelenetz, chair of the NCCN Non-Hodgkin Lymphomas Guidelines panel, presented guideline updates for non-Hodgkin lymphomas.

Click on the PDF icon at the top of this introduction to read the full article.

At the 2014 National Comprehensive Cancer Network annual conference in Hollywood, Florida, Dr Andrew D Zelenetz, chair of the NCCN Non-Hodgkin Lymphomas Guidelines panel, presented guideline updates for non-Hodgkin lymphomas.

Click on the PDF icon at the top of this introduction to read the full article.

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of chronic myeloid leukemia (CML) has made it possible for this cancer to be controlled in many patients for long periods with chronic medication and regular monitoring of disease status. Hematologic and cytogenetic testing, molecular monitoring, and BCR-ABL1 mutational analysis have become integral to the routine management of CML. The information that each type of test provides is essential to confirm a diagnosis, determine the disease stage, assess response to treatment, and monitor for signals of disease progression – all of which can be used to identify patients who might require further evaluation, closer follow-up, and additional intervention, and to guide clinical decisions.


Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of chronic myeloid leukemia (CML) has made it possible for this cancer to be controlled in many patients for long periods with chronic medication and regular monitoring of disease status. Hematologic and cytogenetic testing, molecular monitoring, and BCR-ABL1 mutational analysis have become integral to the routine management of CML. The information that each type of test provides is essential to confirm a diagnosis, determine the disease stage, assess response to treatment, and monitor for signals of disease progression – all of which can be used to identify patients who might require further evaluation, closer follow-up, and additional intervention, and to guide clinical decisions.


Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of chronic myeloid leukemia (CML) has made it possible for this cancer to be controlled in many patients for long periods with chronic medication and regular monitoring of disease status. Hematologic and cytogenetic testing, molecular monitoring, and BCR-ABL1 mutational analysis have become integral to the routine management of CML. The information that each type of test provides is essential to confirm a diagnosis, determine the disease stage, assess response to treatment, and monitor for signals of disease progression – all of which can be used to identify patients who might require further evaluation, closer follow-up, and additional intervention, and to guide clinical decisions.


Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

When I was in high school, one of my friends told me he intended to kill another one of my friends. It was a different day and age back then, and with more than 4,000 students, my high school was rather large and impersonal – it was easy to get lost in the crowd.

"Juan" (not his real name) confided in me that he wanted to kill "Joe" (also not his real name), which I found a bit odd. Joe was well liked but not did really stand out. Juan was perhaps quieter and more studious, but he also did not stand out. Both boys had friends, did well in school, and were not obviously troubled. When I asked Juan why he wanted to kill Joe, he responded, "Because he’s the all-American boy."

I worried about this. I told my mother, and I told a teacher I trusted. No one knew what to do, and Juan’s plan did not sound feasible. He was going to bring a knife to school in a folder, and when Joe was walking in a crowded hallway, Juan would walk behind him and thrust out the folder to sent the knife flying. The physics of this just didn’t make sense to me, and I didn’t see how the knife would gain enough momentum to travel very far, much less penetrate a person through their clothes. Feasible, or not, however, the equation changed on a day that Juan and I were sitting together in the back row of Latin class. Juan opened his calculus book and showed me the butcher knife.

I excused myself from class, went to a pay phone, and called my mother. She called the school, the principal called the police, and Juan was quietly removed from school when the period ended. It would be hard to imagine that a teenager who plotted the murder of another student, by illogical means for an illogical reason, wasn’t emotionally disturbed. I don’t know what happens to someone like Juan in 2014 – I’m thinking nothing good – but let me tell you what happened to Juan in the late 1970s.

Juan was out of high school for 6 weeks. I heard he had psychological testing, but aside from that, I have no idea what transpired. One of his friends told me it was a joke. He returned to high school, never said another word to me, graduated, and attended an Ivy League university – one of several prestigious schools to which he gained admission. A Google search reveals that Juan later earned a graduate degree and works as an executive making a six-figure salary. (Isn’t Google great?) He’s an adjunct professor at a college where he gets glowing reviews on RateMyProfessors.com. He was elected to serve on a local government committee. He’s married and has children. Compliments of Facebook, I know that he continues to have contact with high school friends.

From what I can tell, Juan’s brief period of being a disturbed adolescent did not progress to a life defined by chronic mental illness, and he did not go on to become a violent felon. I have no idea if I did Juan a favor, prevented a murder, got him much-needed treatment, or simply added an embarrassing diversion to his life. I don’t know if he ever really would have harmed Joe, or if it was in fact a joke designed to yank my chain.

Apparently, my threshold is on the low side, and not long ago I called a friend late one night and insisted she check on her teenager when a Facebook post struck me as alarming and a bit too final. The response I got was, "They were lyrics from a song and you’re overreacting." So be it. I called the mother and not the National Guard, and if the teen had become a statistic, I would have regretted not reacting.

I did wonder, while writing this article, how it would be received if I were to contact Juan and ask his thoughts on those events decades ago. Somehow, it seemed best not to uncover old wounds.

The media talk about the dangerously mentally ill as though they are a separate breed of humans, ones who can be easily distinguished by simply assessing who stands on which side of a well-marked "us-versus-them" line. Human beings, especially young human beings, may go through phases, and they may struggle with controlling their emotions, behaviors, and impulses and with finding their identity at a time in life when fitting in has undue importance. Some of them, no doubt, have these crises in the throes of an acute episode of mental distress – illness, if you’d prefer – and others do so at the genesis of what will prove to be a chronic and persistent psychiatric disorder. It may not be clear at any given moment who is going through a phase, who is suffering from an acute episode of mental illness, and who is beginning their course of a severe and persistent disorder.

Still, there are those who want to neatly categorize those with "serious" mental illness so that we can focus more of our resources on their needs and not on those who they deem to be the "worried well." Juan, it appears, did not fall into that category of chronically or persistently mentally ill. Similarly, all of us know chaotic, misbehaving, and even suicidal teenagers who go on to live productive lives. Does that designation matter if those not-so-seriously (or not-so-obviously) mentally ill individuals kill someone or die during their brief moments of emotional turbulence?

It seems to me that the goal is to keep people safe and help usher them through difficult periods in their lives, regardless of any diagnostic certainty or severity. I would contend that the mentally healthy among us also are subject to impulsive, distressed, and dangerous moments and that the world does not always neatly divide people into proper categorical entities.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

When I was in high school, one of my friends told me he intended to kill another one of my friends. It was a different day and age back then, and with more than 4,000 students, my high school was rather large and impersonal – it was easy to get lost in the crowd.

"Juan" (not his real name) confided in me that he wanted to kill "Joe" (also not his real name), which I found a bit odd. Joe was well liked but not did really stand out. Juan was perhaps quieter and more studious, but he also did not stand out. Both boys had friends, did well in school, and were not obviously troubled. When I asked Juan why he wanted to kill Joe, he responded, "Because he’s the all-American boy."

I worried about this. I told my mother, and I told a teacher I trusted. No one knew what to do, and Juan’s plan did not sound feasible. He was going to bring a knife to school in a folder, and when Joe was walking in a crowded hallway, Juan would walk behind him and thrust out the folder to sent the knife flying. The physics of this just didn’t make sense to me, and I didn’t see how the knife would gain enough momentum to travel very far, much less penetrate a person through their clothes. Feasible, or not, however, the equation changed on a day that Juan and I were sitting together in the back row of Latin class. Juan opened his calculus book and showed me the butcher knife.

I excused myself from class, went to a pay phone, and called my mother. She called the school, the principal called the police, and Juan was quietly removed from school when the period ended. It would be hard to imagine that a teenager who plotted the murder of another student, by illogical means for an illogical reason, wasn’t emotionally disturbed. I don’t know what happens to someone like Juan in 2014 – I’m thinking nothing good – but let me tell you what happened to Juan in the late 1970s.

Juan was out of high school for 6 weeks. I heard he had psychological testing, but aside from that, I have no idea what transpired. One of his friends told me it was a joke. He returned to high school, never said another word to me, graduated, and attended an Ivy League university – one of several prestigious schools to which he gained admission. A Google search reveals that Juan later earned a graduate degree and works as an executive making a six-figure salary. (Isn’t Google great?) He’s an adjunct professor at a college where he gets glowing reviews on RateMyProfessors.com. He was elected to serve on a local government committee. He’s married and has children. Compliments of Facebook, I know that he continues to have contact with high school friends.

From what I can tell, Juan’s brief period of being a disturbed adolescent did not progress to a life defined by chronic mental illness, and he did not go on to become a violent felon. I have no idea if I did Juan a favor, prevented a murder, got him much-needed treatment, or simply added an embarrassing diversion to his life. I don’t know if he ever really would have harmed Joe, or if it was in fact a joke designed to yank my chain.

Apparently, my threshold is on the low side, and not long ago I called a friend late one night and insisted she check on her teenager when a Facebook post struck me as alarming and a bit too final. The response I got was, "They were lyrics from a song and you’re overreacting." So be it. I called the mother and not the National Guard, and if the teen had become a statistic, I would have regretted not reacting.

I did wonder, while writing this article, how it would be received if I were to contact Juan and ask his thoughts on those events decades ago. Somehow, it seemed best not to uncover old wounds.

The media talk about the dangerously mentally ill as though they are a separate breed of humans, ones who can be easily distinguished by simply assessing who stands on which side of a well-marked "us-versus-them" line. Human beings, especially young human beings, may go through phases, and they may struggle with controlling their emotions, behaviors, and impulses and with finding their identity at a time in life when fitting in has undue importance. Some of them, no doubt, have these crises in the throes of an acute episode of mental distress – illness, if you’d prefer – and others do so at the genesis of what will prove to be a chronic and persistent psychiatric disorder. It may not be clear at any given moment who is going through a phase, who is suffering from an acute episode of mental illness, and who is beginning their course of a severe and persistent disorder.

Still, there are those who want to neatly categorize those with "serious" mental illness so that we can focus more of our resources on their needs and not on those who they deem to be the "worried well." Juan, it appears, did not fall into that category of chronically or persistently mentally ill. Similarly, all of us know chaotic, misbehaving, and even suicidal teenagers who go on to live productive lives. Does that designation matter if those not-so-seriously (or not-so-obviously) mentally ill individuals kill someone or die during their brief moments of emotional turbulence?

It seems to me that the goal is to keep people safe and help usher them through difficult periods in their lives, regardless of any diagnostic certainty or severity. I would contend that the mentally healthy among us also are subject to impulsive, distressed, and dangerous moments and that the world does not always neatly divide people into proper categorical entities.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

When I was in high school, one of my friends told me he intended to kill another one of my friends. It was a different day and age back then, and with more than 4,000 students, my high school was rather large and impersonal – it was easy to get lost in the crowd.

"Juan" (not his real name) confided in me that he wanted to kill "Joe" (also not his real name), which I found a bit odd. Joe was well liked but not did really stand out. Juan was perhaps quieter and more studious, but he also did not stand out. Both boys had friends, did well in school, and were not obviously troubled. When I asked Juan why he wanted to kill Joe, he responded, "Because he’s the all-American boy."

I worried about this. I told my mother, and I told a teacher I trusted. No one knew what to do, and Juan’s plan did not sound feasible. He was going to bring a knife to school in a folder, and when Joe was walking in a crowded hallway, Juan would walk behind him and thrust out the folder to sent the knife flying. The physics of this just didn’t make sense to me, and I didn’t see how the knife would gain enough momentum to travel very far, much less penetrate a person through their clothes. Feasible, or not, however, the equation changed on a day that Juan and I were sitting together in the back row of Latin class. Juan opened his calculus book and showed me the butcher knife.

I excused myself from class, went to a pay phone, and called my mother. She called the school, the principal called the police, and Juan was quietly removed from school when the period ended. It would be hard to imagine that a teenager who plotted the murder of another student, by illogical means for an illogical reason, wasn’t emotionally disturbed. I don’t know what happens to someone like Juan in 2014 – I’m thinking nothing good – but let me tell you what happened to Juan in the late 1970s.

Juan was out of high school for 6 weeks. I heard he had psychological testing, but aside from that, I have no idea what transpired. One of his friends told me it was a joke. He returned to high school, never said another word to me, graduated, and attended an Ivy League university – one of several prestigious schools to which he gained admission. A Google search reveals that Juan later earned a graduate degree and works as an executive making a six-figure salary. (Isn’t Google great?) He’s an adjunct professor at a college where he gets glowing reviews on RateMyProfessors.com. He was elected to serve on a local government committee. He’s married and has children. Compliments of Facebook, I know that he continues to have contact with high school friends.

From what I can tell, Juan’s brief period of being a disturbed adolescent did not progress to a life defined by chronic mental illness, and he did not go on to become a violent felon. I have no idea if I did Juan a favor, prevented a murder, got him much-needed treatment, or simply added an embarrassing diversion to his life. I don’t know if he ever really would have harmed Joe, or if it was in fact a joke designed to yank my chain.

Apparently, my threshold is on the low side, and not long ago I called a friend late one night and insisted she check on her teenager when a Facebook post struck me as alarming and a bit too final. The response I got was, "They were lyrics from a song and you’re overreacting." So be it. I called the mother and not the National Guard, and if the teen had become a statistic, I would have regretted not reacting.

I did wonder, while writing this article, how it would be received if I were to contact Juan and ask his thoughts on those events decades ago. Somehow, it seemed best not to uncover old wounds.

The media talk about the dangerously mentally ill as though they are a separate breed of humans, ones who can be easily distinguished by simply assessing who stands on which side of a well-marked "us-versus-them" line. Human beings, especially young human beings, may go through phases, and they may struggle with controlling their emotions, behaviors, and impulses and with finding their identity at a time in life when fitting in has undue importance. Some of them, no doubt, have these crises in the throes of an acute episode of mental distress – illness, if you’d prefer – and others do so at the genesis of what will prove to be a chronic and persistent psychiatric disorder. It may not be clear at any given moment who is going through a phase, who is suffering from an acute episode of mental illness, and who is beginning their course of a severe and persistent disorder.

Still, there are those who want to neatly categorize those with "serious" mental illness so that we can focus more of our resources on their needs and not on those who they deem to be the "worried well." Juan, it appears, did not fall into that category of chronically or persistently mentally ill. Similarly, all of us know chaotic, misbehaving, and even suicidal teenagers who go on to live productive lives. Does that designation matter if those not-so-seriously (or not-so-obviously) mentally ill individuals kill someone or die during their brief moments of emotional turbulence?

It seems to me that the goal is to keep people safe and help usher them through difficult periods in their lives, regardless of any diagnostic certainty or severity. I would contend that the mentally healthy among us also are subject to impulsive, distressed, and dangerous moments and that the world does not always neatly divide people into proper categorical entities.

Dr. Miller is a coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011).

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

Physicians should screen all asymptomatic but high-risk adolescents and adults for hepatitis B virus infection, according to an updated recommendation by the U.S. Preventive Services Task Force that was published online May 27 in Annals of Internal Medicine.

Since the last USPSTF recommendation on HBV screening in 2004, which focused on the general population and didn’t advocate screening of this subset of patients, research has documented that antiviral treatment improves both intermediate outcomes such as virologic and histologic responses and long-term outcomes such as prevention of hepatocellular carcinoma, cirrhosis, and end-stage liver disease.

Given this effectiveness, along with the 98% sensitivity and specificity of HBV screening tests, the group has now issued a level B recommendation that high-risk patients be screened, said Dr. Michael L. LeFevre, chair of the USPSTF and professor of family and community medicine at the University of Missouri, Columbia, and his associates.

High-risk patients include the following:

• People born in regions where the prevalence of HBV infection is 2% or greater, such as sub-Saharan Africa, central and southeast Asia, China, the Pacific Islands, and parts of Latin America. People born in these areas account for 47%-95% of the chronic HBV infection in the United States.

• American-born children of parents from these regions, who may not have been vaccinated in infancy.

• HIV-positive persons.

• IV-drug users.

• Household contacts of people with HBV infection.

• Men who have sex with men.

The updated USPSTF recommendations are in line with those of the Centers for Disease Control and Prevention, the American Association for the Study of Liver Diseases, the Institute of Medicine, and the American Academy of Family Physicians. The CDC additionally recommends HBV screening for blood, organ, or tissue donors; people with occupational or other exposure to infectious blood or body fluids; and patients receiving hemodialysis, cytotoxic therapy, or immunosuppressive therapy.

The USPSTF still does not recommend HBV screening for the general population. The prevalence of the infection is low in the U.S. general population, and most members of the general population who are infected with HBV do not develop the chronic form of the infection and do not develop complications like hepatocellular carcinoma or cirrhosis. The potential harms of general screening, then, probably exceed the potential benefits, Dr. LeFevre and his associates noted (Ann Intern. Med. 2014 May 27 [doi:10.7326/M14-1018]).

The USPSTF has separate recommendations regarding hepatitis B in pregnant women. These, along with the updated recommendations for high-risk patients, are available at www.uspreventiveservicestaskforce.org.

The USPSTF is a voluntary group funded by the Agency for Healthcare Research and Quality but otherwise independent of the federal government. Dr. LeFevre and his associates reported no potential financial conflicts of interest.

Physicians should screen all asymptomatic but high-risk adolescents and adults for hepatitis B virus infection, according to an updated recommendation by the U.S. Preventive Services Task Force that was published online May 27 in Annals of Internal Medicine.

Since the last USPSTF recommendation on HBV screening in 2004, which focused on the general population and didn’t advocate screening of this subset of patients, research has documented that antiviral treatment improves both intermediate outcomes such as virologic and histologic responses and long-term outcomes such as prevention of hepatocellular carcinoma, cirrhosis, and end-stage liver disease.

Given this effectiveness, along with the 98% sensitivity and specificity of HBV screening tests, the group has now issued a level B recommendation that high-risk patients be screened, said Dr. Michael L. LeFevre, chair of the USPSTF and professor of family and community medicine at the University of Missouri, Columbia, and his associates.

High-risk patients include the following:

• People born in regions where the prevalence of HBV infection is 2% or greater, such as sub-Saharan Africa, central and southeast Asia, China, the Pacific Islands, and parts of Latin America. People born in these areas account for 47%-95% of the chronic HBV infection in the United States.

• American-born children of parents from these regions, who may not have been vaccinated in infancy.

• HIV-positive persons.

• IV-drug users.

• Household contacts of people with HBV infection.

• Men who have sex with men.

The updated USPSTF recommendations are in line with those of the Centers for Disease Control and Prevention, the American Association for the Study of Liver Diseases, the Institute of Medicine, and the American Academy of Family Physicians. The CDC additionally recommends HBV screening for blood, organ, or tissue donors; people with occupational or other exposure to infectious blood or body fluids; and patients receiving hemodialysis, cytotoxic therapy, or immunosuppressive therapy.

The USPSTF still does not recommend HBV screening for the general population. The prevalence of the infection is low in the U.S. general population, and most members of the general population who are infected with HBV do not develop the chronic form of the infection and do not develop complications like hepatocellular carcinoma or cirrhosis. The potential harms of general screening, then, probably exceed the potential benefits, Dr. LeFevre and his associates noted (Ann Intern. Med. 2014 May 27 [doi:10.7326/M14-1018]).

The USPSTF has separate recommendations regarding hepatitis B in pregnant women. These, along with the updated recommendations for high-risk patients, are available at www.uspreventiveservicestaskforce.org.

The USPSTF is a voluntary group funded by the Agency for Healthcare Research and Quality but otherwise independent of the federal government. Dr. LeFevre and his associates reported no potential financial conflicts of interest.

Physicians should screen all asymptomatic but high-risk adolescents and adults for hepatitis B virus infection, according to an updated recommendation by the U.S. Preventive Services Task Force that was published online May 27 in Annals of Internal Medicine.

Since the last USPSTF recommendation on HBV screening in 2004, which focused on the general population and didn’t advocate screening of this subset of patients, research has documented that antiviral treatment improves both intermediate outcomes such as virologic and histologic responses and long-term outcomes such as prevention of hepatocellular carcinoma, cirrhosis, and end-stage liver disease.

Given this effectiveness, along with the 98% sensitivity and specificity of HBV screening tests, the group has now issued a level B recommendation that high-risk patients be screened, said Dr. Michael L. LeFevre, chair of the USPSTF and professor of family and community medicine at the University of Missouri, Columbia, and his associates.

High-risk patients include the following:

• People born in regions where the prevalence of HBV infection is 2% or greater, such as sub-Saharan Africa, central and southeast Asia, China, the Pacific Islands, and parts of Latin America. People born in these areas account for 47%-95% of the chronic HBV infection in the United States.

• American-born children of parents from these regions, who may not have been vaccinated in infancy.

• HIV-positive persons.

• IV-drug users.

• Household contacts of people with HBV infection.

• Men who have sex with men.

The updated USPSTF recommendations are in line with those of the Centers for Disease Control and Prevention, the American Association for the Study of Liver Diseases, the Institute of Medicine, and the American Academy of Family Physicians. The CDC additionally recommends HBV screening for blood, organ, or tissue donors; people with occupational or other exposure to infectious blood or body fluids; and patients receiving hemodialysis, cytotoxic therapy, or immunosuppressive therapy.

The USPSTF still does not recommend HBV screening for the general population. The prevalence of the infection is low in the U.S. general population, and most members of the general population who are infected with HBV do not develop the chronic form of the infection and do not develop complications like hepatocellular carcinoma or cirrhosis. The potential harms of general screening, then, probably exceed the potential benefits, Dr. LeFevre and his associates noted (Ann Intern. Med. 2014 May 27 [doi:10.7326/M14-1018]).

The USPSTF has separate recommendations regarding hepatitis B in pregnant women. These, along with the updated recommendations for high-risk patients, are available at www.uspreventiveservicestaskforce.org.

The USPSTF is a voluntary group funded by the Agency for Healthcare Research and Quality but otherwise independent of the federal government. Dr. LeFevre and his associates reported no potential financial conflicts of interest.