Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring. 

The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities. 

Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.

Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.

Verdict A $10 million Washington settlement was reached.

Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale. 

Patient’s claim The risks and benefits of the OC were not fully explained  to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.

Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.

Verdict A Washington defense verdict was returned. 

Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous ­pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed. 

Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.

Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.

Verdict A $484,141 Mississippi verdict was returned.

Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her. 

Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.

Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.

Verdict A $270,000 Washington verdict was returned.

Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.

The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.

The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel. 

Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.

Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with post­anesthesia residuals.

Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.

Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.

The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.

The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.

The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care. 

Parents’ claim The mother and fetus were never properly assessed or treated. 

Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.

Verdict A Texas defense verdict was returned.

Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care. 

Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.

Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.

Verdict An $8.4 million Georgia verdict was returned.

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.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring. 

The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities. 

Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.

Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.

Verdict A $10 million Washington settlement was reached.

Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale. 

Patient’s claim The risks and benefits of the OC were not fully explained  to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.

Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.

Verdict A Washington defense verdict was returned. 

Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous ­pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed. 

Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.

Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.

Verdict A $484,141 Mississippi verdict was returned.

Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her. 

Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.

Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.

Verdict A $270,000 Washington verdict was returned.

Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.

The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.

The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel. 

Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.

Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with post­anesthesia residuals.

Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.

Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.

The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.

The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.

The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care. 

Parents’ claim The mother and fetus were never properly assessed or treated. 

Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.

Verdict A Texas defense verdict was returned.

Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care. 

Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.

Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.

Verdict An $8.4 million Georgia verdict was returned.

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.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring. 

The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities. 

Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.

Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.

Verdict A $10 million Washington settlement was reached.

Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale. 

Patient’s claim The risks and benefits of the OC were not fully explained  to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.

Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.

Verdict A Washington defense verdict was returned. 

Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous ­pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed. 

Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.

Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.

Verdict A $484,141 Mississippi verdict was returned.

Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her. 

Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.

Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.

Verdict A $270,000 Washington verdict was returned.

Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.

The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.

The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel. 

Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.

Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with post­anesthesia residuals.

Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.

Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.

The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.

The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.

The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care. 

Parents’ claim The mother and fetus were never properly assessed or treated. 

Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.

Verdict A Texas defense verdict was returned.

Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care. 

Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.

Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.

Verdict An $8.4 million Georgia verdict was returned.

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.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.

In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.

In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.

Click here for patient information on epilepsy basics.

Click here for patient information on epilepsy basics.

Click here for patient information on epilepsy basics.

Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Practically everyone who lives in America has heard about the Baltimore riots, precipitated by the death of a man while in police custody. Their scope was unprecedented; their implications, far reaching. I, like many Americans, stayed glued to the news to keep abreast of the latest updates for a variety of reasons, one of which was that I live and work nearby, and personal safety was a major concern. At the peak of the violence, when people were leaving the city in droves, I kept in close contact with my brother, a physician who works in a hospital at the epicenter of the chaos. Fortunately, he got out safely, as did most people. Yet many, including citizens and police officers, were injured, some seriously so.

No matter where you stand regarding the events surrounding the riots, the fact remains that we as physicians are not infrequently called upon to care for patients who have victimized or been victimized by others. We care for those who are slowly destroying themselves and endangering others with their abuse of drugs and alcohol, yet refuse any help we offer for their substance abuse. Some hospitalists work in hospitals with booming prison wards, and thus frequently care for murderers, thieves, child abusers, and others whom we may secretly fear, yet openly pledge to protect, respect, and care for. While I could not find a good scholarly article addressing how we as physicians do versus how we should handle these situations, I believe many of us have struggled with the personal emotions and ethical dilemmas raised by some of these cases.

How much can we and should we get involved? How do we mask our personal opinions of patients who have committed egregious acts and provide not only the best care possible, but do so while treating them with the respect and dignity that we allow for other patients? And if we go the extra mile to provide emotional support and encouragement, will we really have any positive impact on them, or will they just shut us out? Where do we draw the line between just being health care providers and being compassionate, nonjudgmental clinicians who can really impact their lives?

I don’t think there is an easy answer to any of these questions, and each patient is different. But I believe that many people still look up to their health care providers, and there will be those times when we can be more than their doctor; we can be their (much-needed) friend. Meanwhile, we need to guard against the natural human inclination to act as judge and jury toward those who have committed acts we personally find reprehensible. Every patient deserves our very best medical care, even when we cannot find it within ourselves to give this service with a smile.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Donated blood

Photo by Elise Amendola

Chemists have generated an enzyme that shows the potential for converting type A or B blood into a universal blood type.

The enzyme works by snipping off the antigens found in blood types A and B, making these blood types more like O, which can be given to patients of all blood types.

The enzyme was able to remove most of the antigens in type A and B blood. Before it can be used in clinical settings, however, all of the antigens would need to be removed.

David Kwan, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues described their work with this enzyme in the Journal of the American Chemical Society.

“We produced a mutant enzyme that is very efficient at cutting off the sugars in A and B blood and is much more proficient at removing the subtypes of the A antigen that the parent enzyme struggles with,” Dr Kwan said.

To create the enzyme, Dr Kwan and his colleagues used a technology called directed evolution. It involves inserting mutations into the gene that codes for the enzyme and selecting mutants that are more effective at cutting the antigens.

The team started with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A and B antigens from some of the linkages on red blood cell surface glycans.

Through directed evolution, the researchers developed variants of Sp3GH98 that showed improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme.

In 5 generations, the enzyme became 170 times more effective. This Sp3GH98 variant could remove the majority of the antigens in type A and B blood.

The researchers said the enzyme must be able to remove all of the antigens before it can be used in the clinic. The immune system is highly sensitive to blood groups, and even small amounts of residual antigens could trigger an immune response.

The concept of using an enzyme to change blood types is not new, said study author Steve Withers, PhD, also from the University of British Columbia.

“But, until now, we needed so much of the enzyme to make it work that it was impractical,” he said. “Now, I’m confident that we can take this a whole lot further.”

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Blood sample collection

Photo by Juan D. Alfonso

The current method used to identify resistance to the antimalarial drug artemisinin is not entirely accurate, according to research published in PLOS Medicine.

Artemisinin rapidly clears malaria parasites from the blood of infected patients. When parasites develop resistance, clearance takes longer.

The best measure of parasite clearance is the parasite half-life in a patient’s blood, and a common cutoff used to denote artemisinin resistance is 5 hours.

Study author Lisa White, of Mahidol University in Bangkok, Thailand, and her colleagues found that parasite half-life predicts the likelihood of an artemisinin-resistant infection for individual patients. But the half-life is influenced by how common resistance is in the particular area.

The critical half-life varied between 3.5 hours in areas where resistance is rare to 5.5 hours in areas where resistance is common. This means there is no universal cutoff value in parasite half-life that can determine whether a particular infection is “sensitive” or “resistant” to artemisinin-based combination (ACT) therapy.

Because measuring the parasite half-life requires frequent blood sampling that is difficult to do in resource-limited settings, the World Health Organization (WHO) uses the following working definition for surveillance. Artemisinin resistance in a population is suspected if more than 10% of patients are still carrying parasites 3 days after the start of ACT.

Arguing that the cutoff used in the WHO’s working definition is based on limited data, the researchers examined how well the definition matches actual data from patients in areas with artemisinin-resistant parasites.

Applying a model specifically developed for this purpose, the team found that the WHO’s day-3 cutoff value of 10% is useful, but it would be more informative if the parasite load at the start of ACT was taken into account.

The researchers concluded that the WHO definition alone cannot be used to accurately predict the real proportion of artemisinin-resistant parasites, so a more detailed assessment is needed.

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Decreased ability to identify odors may be a marker of acute structural neuropathology resulting from trauma, according to research published online ahead of print March 18 in Neurology. Quantitative identification olfactometry has limited sensitivity but high specificity in detecting this pathology and could inform decisions about whether advanced neuroimaging is required, said the authors.

Michael S. Xydakis, MD, a colonel in the US Air Force and Associate Professor of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues enrolled 231 consecutive patients with polytrauma in a study to determine whether a quantitative assessment of differential olfactory performance could serve as a reliable antecedent marker for the preclinical detection of intracranial neurotrauma. Participants had been acutely injured from explosions during combat operations in Afghanistan or Iraq, required immediate stateside evacuation, and were enrolled prospectively during two and a half years.

All patients underwent evaluation for possible traumatic brain injury (TBI). The investigators stratified the patients into groups according to severity of TBI and neuroimaging results. Blast-injured troops without TBI who had comparable demographic features and severity of polytrauma formed the comparison control group. An otorhinolaryngologist administered the University of Pennsylvania Smell Identification Test to each patient. Patients were described as having normal, decreased, or absent olfactory function, and the latter two categories were considered to represent olfactory impairment.

Impairment Associated With Frontal and Temporal Lobe Injuries
Approximately 6% of participants had impaired olfactory function. All patients in the mild TBI group and the blast-injured control group had normal olfactory function. Median olfactometric scores did not differ significantly between these two groups. All participants with normal neuroimaging, including 127 patients with mild TBI and 47 controls, had normal olfactory function.

Among the 40 patients with abnormal imaging, 35% had olfactory impairment. Data analysis indicated that olfactometric score predicted abnormal neuroimaging significantly better than chance alone. Olfactory testing was administered to 18 of the patients with abnormal imaging within 14 days after injury. Nine of these patients had impaired function. The remaining 22 soldiers with abnormal imaging underwent testing 15 or more days after injury, and five of them had impaired function. “These results suggest that it is worth testing the hypothesis that sensitivity of olfactory testing to identify patients with structural brain injury may be higher if testing is performed closer to the time of injury,” said Dr. Xydakis.

Approximately 79% of patients with olfactory impairment had injury to the frontal lobe, compared with 42% of patients with normal olfactory function. About 86% of troops with olfactory impairment had either frontal or temporal involvement, compared with 50% of patients with normal function. Approximately 36% of troops with olfactory impairment had both frontal and temporal involvement, compared with 12% of patients with normal function.

Test May Detect Injury Preclinically
“The radiographic findings support a higher-order CNS etiology for the observed impairment,” said Dr. Xydakis. The inclusion of the blast-injured control group with normal olfactometric scores may mitigate the concern that observed impairments resulted from peripheral trauma at the intranasal receptor level.

The finding that only troops with concurrent acute traumatic radiographic abnormalities had olfactory impairment “supports the assertion that impaired olfactory identification is only present in the context of significant intracranial neurotrauma,” he added. “Ultimately, it is the radiographic presence and the radiographic locations of the structural brain injuries that define the probability of subsequent olfactory performance degradation, and not simply the abstract and unquantifiable risk factor of a ‘blow or hit to the head region.’

“The presence of measurable abnormalities with central olfactory dysfunction provides added value to the practicing physician for preclinical detection of intracranial injury and, accordingly, subsequent disease-modifying early interventions,” Dr. Xydakis continued. “While the level of sensitivity for screening purposes is insufficient to exclude all types of post-traumatic neuropathology, the absolute specificity and the association with frontal or temporal lobe injury enhance its value in clinical practice.”

—Erik Greb

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

Patients 55 and older who present to inpatient and emergency department settings with a traumatic brain injury (TBI) have a 44% increased risk of developing Parkinson’s disease over five to seven years, compared with patients in the same age group who present with non-TBI trauma (NTT), according to research published online ahead of print February 27 in Annals of Neurology. In addition, the risk of developing Parkinson’s disease doubles following more severe or more frequent TBI, compared with mild or single TBI. This finding supports a causal association between TBI and Parkinson’s disease.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues analyzed International Classification of Diseases, Ninth Revision code data collected at California hospitals from 2005 to 2006 to evaluate the risk of developing Parkinson’s disease after TBI in older adulthood. Because of the theoretical possibility that patients with incipient Parkinson’s disease are more likely to fall and sustain a TBI than healthy controls, the researchers examined patients with NTT—defined as fracture, excluding fractures of the head and neck—to reduce possible confounding and reverse causation. To reduce the chance of reverse causation further, researchers excluded cases in which Parkinson’s disease was diagnosed less than a year after the injury.

Researchers identified 52,393 patients with TBI and 113,406 patients with NTT who survived hospitalization and did not have Parkinson’s disease or dementia at baseline. Using Kaplan–Meier estimates and Cox proportional hazards models adjusted for age, sex, race or ethnicity, income, comorbidities, health care use, and trauma severity, they estimated the risk of Parkinson’s disease after TBI during follow-up ending in 2011.

Patients With TBI Were Diagnosed Sooner
Patients with TBI were significantly more likely to be diagnosed with Parkinson’s disease, compared with NTT patients (1.7% of patients vs 1.1% of patients), and patients with TBI were diagnosed with Parkinson’s disease slightly sooner than those with NTT (at 3.1 years, compared with 3.3 years). Researchers found that risk of Parkinson’s disease was similar for TBI sustained via falls and for TBI sustained through other mechanisms.

Researchers also assessed the effect of TBI severity and TBI frequency and found a significant dose response. Patients with mild TBI were 24% more likely to develop Parkinson’s disease, and patients with moderate to severe TBI were 50% more likely to develop Parkinson’s disease, compared with those with NTT. “The evidence for a dose response for increasing TBI severity and TBI frequency, and our persistently significant results despite multiple additional analyses, all enhance causal inference,” the authors said.

A causal association between TBI and Parkinson’s disease may be explained by several possible mechanisms, the researchers said. TBI may reduce motor reserve, thus leading to an earlier diagnosis of Parkinson’s disease in susceptible patients. TBI also may accelerate or augment a pre-existing neurodegenerative cascade or trigger a de novo neurodegenerative cascade. The question of whether typical Parkinson’s disease neuropathologies or unique TBI-specific neuropathology causes post-TBI syndromes deserves further study, they said.

Studies using animal models support a causal mechanism for post-TBI Parkinson’s disease. For example, a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the substantia nigra have been found in rats after experimentally induced TBI. Other research has begun to replicate these findings in humans.

Information About Patients Was Limited
The study’s limitations include the use of administrative diagnostic codes, which may be poorly sensitive or specific to Parkinson’s disease diagnoses. The researchers lacked information regarding patients’ medical histories and other data about patients’ treatments and outcomes. Also, post-traumatic motor or behavioral abnormalities may complicate the diagnosis of Parkinson’s disease, and diagnoses were not verified by expert review. In addition, the use of a trauma control group essentially controlled for any additional harmful effects of trauma on the nervous system that potentially could increase risk of Parkinson’s disease independently. It is important for large-scale prospective studies, ideally with autopsy confirmation, to confirm these findings, the investigators said.

The results are in line with a 2013 meta-analysis of 22 studies that reported a pooled odds ratio of 1.57 for the association between Parkinson’s disease and head trauma, the authors said. When considered with other studies, including prior research by Dr. Gardner’s team that identified a 26% increased risk of dementia after TBI versus NTT in this population, the results “suggest that TBI is an important independent risk factor for a variety of neurodegenerative syndromes.”

The findings also highlight the importance of preventing falls, which caused approximately 66% of trauma in the TBI and NTT groups. “As the cause of trauma in this study was overwhelmingly due to falls, there is critical importance for fall prevention in middle-aged and older adults, not only as a means to prevent bodily injury, but potentially as a means to prevent neurodegenerative diseases such as dementia and Parkinson’s disease,” the authors concluded.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.

In “How is insomnia treated?” the National Heart, Lung & Blood Institute covers the basics about commonly used insomnia treatments. Available at http://www.nhlbi.nih.gov/health/health-topics/topics/inso/treatment, this resource describes lifestyle changes, cognitive behavioral therapy, and both prescription and over-the-counter medications.