Ketamine May Help Treat Medically Refractory Migraine Pain

Ketamine, a medication commonly used for pain relief and increasingly used for depression, may help alleviate migraine pain in patients who have not been helped by other treatments, a study suggests.

The trial of 61 patients found that almost 75% had an improvement in their migraine intensity after a three- to seven-day course of inpatient treatment with ketamine. The drug is used to induce general anesthesia, but also provides powerful pain control for patients with many painful conditions in lower doses than its anesthetic use.

“Ketamine may hold promise as a treatment for migraine headaches in patients who have failed other treatments,” said study coauthor Eric Schwenk, MD, Director of Orthopedic Anesthesia at Thomas Jefferson University Hospital in Philadelphia. “Our study focused only on short-term relief, but it is encouraging that this treatment might have the potential to help patients [in the] long-term. Our work provides the basis for future prospective studies that involve larger numbers of patients.”

An estimated 12% of the US population has migraines. A subset of these patients, along with those who have other types of headaches, does not respond to treatment. During a migraine, people are often sensitive to light and sound and may become nauseated or vomit. Migraines are three times more common in women than in men.

The researchers reviewed data for patients who received ketamine infusions for intractable migraine headaches—migraines that had failed all other therapies. On a scale of 0 to 10, the average migraine headache pain rating at admission was 7.5, compared with 3.4 at discharge. The average length of infusion was 5.1 days, and the day of lowest pain ratings was day 4. Adverse effects were generally mild.

Dr. Schwenk said that while his hospital uses ketamine to treat intractable migraines, the treatment is not yet widely available. Thomas Jefferson University Hospital will open a new infusion center that will treat more patients with headaches using ketamine. “We hope to expand its use to both more patients and more conditions in the future,” he said.

“Due to the retrospective nature of the study, we cannot definitively say that ketamine is entirely responsible for the pain relief, but we have provided a basis for additional larger studies to be undertaken,” Dr. Schwenk added.

Opioid Abuse Plateaus at a High Level

Although the rapid increase in opioid abuse has leveled off, the prevalence of abuse remains high and does not appear to be declining, according to an analysis of national data.

More than 13% of Americans age 12 and older—nearly one in seven—have abused prescription opioids at some point in their lives, researchers determined after analyzing the latest data from the National Survey on Drug Use and Health (NSDUH), an annual survey sponsored by the Substance Abuse and Mental Health Services Administration. Additionally, while 8.6% of Americans abused opioids in 2000, by 2003 that number increased to 13.2%, and it has remained at that level since.

“The amount of opioid prescriptions being written in the United States is breathtaking—essentially enough for every American adult to have a bottle of the pain killers in their medicine cabinet,” said Asokumar Buvanendran, MD, lead author of the study, Director of Orthopedic Anesthesia and Vice Chair for Research at Rush Medical College in Chicago, and chair of the American Society of Anesthesiologists (ASA) Committee on Pain Medicine. “This in turn leads to opioid abuse because people may take more than needed, or the pills fall into the wrong hands. That has got to change.”

Because opioids can produce euphoria, they are highly likely to be abused. Opioid prescriptions are often written for an excessive number of pills, so patients may take more medication than they need and become addicted. Additionally, unused medication can be diverted to another person for illicit use. More than half of the people who misuse prescribed opioids get them from a friend or relative, not a physician, according to NSDUH data.

The NSDUH survey asked Americans whether they had taken prescription opioids without a prescription written for them (which constitutes abuse) anytime in their lives. The researchers determined that in 2014 (the last year for which data was available), 13.6% of Americans had abused prescription opioids. Use of hydrocodone (including Vicodin, a combination of hydrocodone and acetaminophen) increased from 3.2% in 2000 to 9.1% in 2014. Use of oxycontin increased from less than 1% in 2000 to 3% in 2014.

Hydrocodone is the most frequently prescribed and therefore the most frequently abused opioid, researchers noted.

“While the illicit opioid use trend seems to have plateaued, there is no evidence of a decline yet,” said Mario Moric, coauthor of the study and a biostatistician at Rush Medical College. “Hopefully, with increased national attention to the problem we will see a significant drop in abuse.”

“Opioids are still an important tool for dealing with pain, but doctors need to prescribe smaller quantities,” said Dr. Buvanendran. “Also, patients need to be educated about the dangers of overuse and abuse and understand that pain usually cannot be solved solely with a pill, but needs to include exercise, physical therapy, eating right, having a social support system, and developing good coping skills.”

The ASA is committed to ending opioid abuse and has launched several initiatives to combat the epidemic.

Botox May Benefit Children With Hard-to-Treat Migraines

Injections of botulinum toxin (Botox) may provide significant relief for children with migraine headaches that do not respond to traditional treatment, suggests a small preliminary study.

Botox is approved by the FDA to treat migraines in adults. One in 10 school-aged children and teens have migraines, but there are few FDA-approved medications for this age group. Some children and teens do not respond well to available options, such as certain migraine rescue pain medications, and the pain and disability of migraines can have a severe impact on their lives. Preventative medications may help sometimes. Only one preventative migraine medication, topiramate, is approved for adolescents, however.

“When children and teens have migraine pain, it can severely affect their lives and ability to function. They miss school, their grades suffer, and they are left behind, often unable to reach their full potential. Clearly, there is a need for an alternative treatment for those who have not found relief,” said Shalini Shah, MD, lead author of the study and Chief of the Division of Pain Medicine at the University of California, Irvine. “After treatment, we saw improvement in functional aspects in all of the children and teens. In fact, one patient was hospitalized monthly for her migraine pain prior to Botox treatment and was expected to be held back in school. After treatment, she only has one or two migraines a year, and is excelling in college.”

The study included nine children and teens (ages 8 to 17) who had migraines on eight to 29.5 days per month. Most participants had tried numerous medications and other therapies without much relief. All received Botox injections in the front and back of the head and neck every 12 weeks and were evaluated during a five-year period. After treatment, the patients had migraines on two to 10 days per month.

In addition, when treated participants did have migraines, their headaches did not last as long. Patients’ migraines lasted from 30 minutes to 24 hours before treatment, and 15 minutes to seven hours after treatment. Their headaches also were not as painful. Patient-reported pain on a scale of 1–10 (from no pain to worst pain imaginable) ranged from 4 to 8 before treatment and 1.75 to 5 after treatment.

Eight adverse events were reported during the study. Most resulted from pain at the injection site. No severe adverse events were reported.

If the results of the current study are confirmed, Botox could provide an alternative for patients without treatment options, said Dr. Shah. Her team is enrolling patients to study this treatment in a prospective, randomized, double-blinded trial to compare Botox with placebo.

“Many current migraine medications have side effects, including sedation, dry mouth, and confusion, which are not well-tolerated in children and teens,” said Dr. Shah. “Our research of Botox is part of an effort to find better treatments for children and teens with migraines so they can realize their full potential.”

The study authors received no funding from the manufacturer of Botox.

Diabetes Increases Risk of Cognitive Problems After Surgery

Older patients with diabetes may be at an 84% higher risk of developing postoperative cognitive dysfunction (POCD) than those who are not diabetic, new research suggests.

“With POCD, a patient’s mental ability declines after surgery, compared to their cognitive performance before surgery, resulting not only in increased complications and potential death, but also impairing the patient’s quality of life,” said Gunnar Lachmann, MD, Department of Anesthesiology and Operative Intensive Care Medicine, Charité—Universitätsmedizin Berlin. “POCD is increasingly recognized as a common complication after major surgery, affecting 10% to 13% of patients, with seniors being especially vulnerable.”

POCD is a major form of cognitive disturbance that can occur after anesthesia and surgery, but little is known about its potential risk factors. An association between diabetes and age-related cognitive impairment is well established, but the role diabetes has in the development of POCD is unknown.

In the study, researchers performed a secondary analysis of three studies, comprising 1,034 patients (481 who had cardiac surgery and 553 who had noncardiac surgery), to examine whether diabetes was a risk factor for POCD. Patients’ mean age was 66.4. Of the 1,034 participants, 18.6% had diabetes. The association of diabetes with risk of POCD was determined using logistic regression models at the longest patient follow-up period for each study, which was three or 12 months. Risk estimates were pooled across all three studies.

After adjusting for age, sex, surgery type, randomization, obesity, and hypertension, the researchers determined that diabetes was associated with an 84% higher risk of POCD. Patients age 65 or older were at particularly high risk.

“Our findings suggest that consideration of diabetes status may be helpful for the assessment of POCD risk among patients undergoing surgery,” said Dr. Lachmann. “Further studies are warranted to examine the potential mechanisms of this association, to ultimately help in the development of potential strategies for prevention.”

In 2015, the American Society of Anesthesiologists launched a patient safety initiative—the Brain Health Initiative—to provide physician anesthesiologists and other clinicians involved in perioperative care, as well as patients and their families caring for older surgical patients, with the tools and resources necessary to optimize the cognitive recovery and perioperative experience for adults age 65 and older undergoing surgery.

Ketamine May Help Treat Medically Refractory Migraine Pain

Ketamine, a medication commonly used for pain relief and increasingly used for depression, may help alleviate migraine pain in patients who have not been helped by other treatments, a study suggests.

The trial of 61 patients found that almost 75% had an improvement in their migraine intensity after a three- to seven-day course of inpatient treatment with ketamine. The drug is used to induce general anesthesia, but also provides powerful pain control for patients with many painful conditions in lower doses than its anesthetic use.

“Ketamine may hold promise as a treatment for migraine headaches in patients who have failed other treatments,” said study coauthor Eric Schwenk, MD, Director of Orthopedic Anesthesia at Thomas Jefferson University Hospital in Philadelphia. “Our study focused only on short-term relief, but it is encouraging that this treatment might have the potential to help patients [in the] long-term. Our work provides the basis for future prospective studies that involve larger numbers of patients.”

An estimated 12% of the US population has migraines. A subset of these patients, along with those who have other types of headaches, does not respond to treatment. During a migraine, people are often sensitive to light and sound and may become nauseated or vomit. Migraines are three times more common in women than in men.

The researchers reviewed data for patients who received ketamine infusions for intractable migraine headaches—migraines that had failed all other therapies. On a scale of 0 to 10, the average migraine headache pain rating at admission was 7.5, compared with 3.4 at discharge. The average length of infusion was 5.1 days, and the day of lowest pain ratings was day 4. Adverse effects were generally mild.

Dr. Schwenk said that while his hospital uses ketamine to treat intractable migraines, the treatment is not yet widely available. Thomas Jefferson University Hospital will open a new infusion center that will treat more patients with headaches using ketamine. “We hope to expand its use to both more patients and more conditions in the future,” he said.

“Due to the retrospective nature of the study, we cannot definitively say that ketamine is entirely responsible for the pain relief, but we have provided a basis for additional larger studies to be undertaken,” Dr. Schwenk added.

Opioid Abuse Plateaus at a High Level

Although the rapid increase in opioid abuse has leveled off, the prevalence of abuse remains high and does not appear to be declining, according to an analysis of national data.

More than 13% of Americans age 12 and older—nearly one in seven—have abused prescription opioids at some point in their lives, researchers determined after analyzing the latest data from the National Survey on Drug Use and Health (NSDUH), an annual survey sponsored by the Substance Abuse and Mental Health Services Administration. Additionally, while 8.6% of Americans abused opioids in 2000, by 2003 that number increased to 13.2%, and it has remained at that level since.

“The amount of opioid prescriptions being written in the United States is breathtaking—essentially enough for every American adult to have a bottle of the pain killers in their medicine cabinet,” said Asokumar Buvanendran, MD, lead author of the study, Director of Orthopedic Anesthesia and Vice Chair for Research at Rush Medical College in Chicago, and chair of the American Society of Anesthesiologists (ASA) Committee on Pain Medicine. “This in turn leads to opioid abuse because people may take more than needed, or the pills fall into the wrong hands. That has got to change.”

Because opioids can produce euphoria, they are highly likely to be abused. Opioid prescriptions are often written for an excessive number of pills, so patients may take more medication than they need and become addicted. Additionally, unused medication can be diverted to another person for illicit use. More than half of the people who misuse prescribed opioids get them from a friend or relative, not a physician, according to NSDUH data.

The NSDUH survey asked Americans whether they had taken prescription opioids without a prescription written for them (which constitutes abuse) anytime in their lives. The researchers determined that in 2014 (the last year for which data was available), 13.6% of Americans had abused prescription opioids. Use of hydrocodone (including Vicodin, a combination of hydrocodone and acetaminophen) increased from 3.2% in 2000 to 9.1% in 2014. Use of oxycontin increased from less than 1% in 2000 to 3% in 2014.

Hydrocodone is the most frequently prescribed and therefore the most frequently abused opioid, researchers noted.

“While the illicit opioid use trend seems to have plateaued, there is no evidence of a decline yet,” said Mario Moric, coauthor of the study and a biostatistician at Rush Medical College. “Hopefully, with increased national attention to the problem we will see a significant drop in abuse.”

“Opioids are still an important tool for dealing with pain, but doctors need to prescribe smaller quantities,” said Dr. Buvanendran. “Also, patients need to be educated about the dangers of overuse and abuse and understand that pain usually cannot be solved solely with a pill, but needs to include exercise, physical therapy, eating right, having a social support system, and developing good coping skills.”

The ASA is committed to ending opioid abuse and has launched several initiatives to combat the epidemic.

Botox May Benefit Children With Hard-to-Treat Migraines

Injections of botulinum toxin (Botox) may provide significant relief for children with migraine headaches that do not respond to traditional treatment, suggests a small preliminary study.

Botox is approved by the FDA to treat migraines in adults. One in 10 school-aged children and teens have migraines, but there are few FDA-approved medications for this age group. Some children and teens do not respond well to available options, such as certain migraine rescue pain medications, and the pain and disability of migraines can have a severe impact on their lives. Preventative medications may help sometimes. Only one preventative migraine medication, topiramate, is approved for adolescents, however.

“When children and teens have migraine pain, it can severely affect their lives and ability to function. They miss school, their grades suffer, and they are left behind, often unable to reach their full potential. Clearly, there is a need for an alternative treatment for those who have not found relief,” said Shalini Shah, MD, lead author of the study and Chief of the Division of Pain Medicine at the University of California, Irvine. “After treatment, we saw improvement in functional aspects in all of the children and teens. In fact, one patient was hospitalized monthly for her migraine pain prior to Botox treatment and was expected to be held back in school. After treatment, she only has one or two migraines a year, and is excelling in college.”

The study included nine children and teens (ages 8 to 17) who had migraines on eight to 29.5 days per month. Most participants had tried numerous medications and other therapies without much relief. All received Botox injections in the front and back of the head and neck every 12 weeks and were evaluated during a five-year period. After treatment, the patients had migraines on two to 10 days per month.

In addition, when treated participants did have migraines, their headaches did not last as long. Patients’ migraines lasted from 30 minutes to 24 hours before treatment, and 15 minutes to seven hours after treatment. Their headaches also were not as painful. Patient-reported pain on a scale of 1–10 (from no pain to worst pain imaginable) ranged from 4 to 8 before treatment and 1.75 to 5 after treatment.

Eight adverse events were reported during the study. Most resulted from pain at the injection site. No severe adverse events were reported.

If the results of the current study are confirmed, Botox could provide an alternative for patients without treatment options, said Dr. Shah. Her team is enrolling patients to study this treatment in a prospective, randomized, double-blinded trial to compare Botox with placebo.

“Many current migraine medications have side effects, including sedation, dry mouth, and confusion, which are not well-tolerated in children and teens,” said Dr. Shah. “Our research of Botox is part of an effort to find better treatments for children and teens with migraines so they can realize their full potential.”

The study authors received no funding from the manufacturer of Botox.

Diabetes Increases Risk of Cognitive Problems After Surgery

Older patients with diabetes may be at an 84% higher risk of developing postoperative cognitive dysfunction (POCD) than those who are not diabetic, new research suggests.

“With POCD, a patient’s mental ability declines after surgery, compared to their cognitive performance before surgery, resulting not only in increased complications and potential death, but also impairing the patient’s quality of life,” said Gunnar Lachmann, MD, Department of Anesthesiology and Operative Intensive Care Medicine, Charité—Universitätsmedizin Berlin. “POCD is increasingly recognized as a common complication after major surgery, affecting 10% to 13% of patients, with seniors being especially vulnerable.”

POCD is a major form of cognitive disturbance that can occur after anesthesia and surgery, but little is known about its potential risk factors. An association between diabetes and age-related cognitive impairment is well established, but the role diabetes has in the development of POCD is unknown.

In the study, researchers performed a secondary analysis of three studies, comprising 1,034 patients (481 who had cardiac surgery and 553 who had noncardiac surgery), to examine whether diabetes was a risk factor for POCD. Patients’ mean age was 66.4. Of the 1,034 participants, 18.6% had diabetes. The association of diabetes with risk of POCD was determined using logistic regression models at the longest patient follow-up period for each study, which was three or 12 months. Risk estimates were pooled across all three studies.

After adjusting for age, sex, surgery type, randomization, obesity, and hypertension, the researchers determined that diabetes was associated with an 84% higher risk of POCD. Patients age 65 or older were at particularly high risk.

“Our findings suggest that consideration of diabetes status may be helpful for the assessment of POCD risk among patients undergoing surgery,” said Dr. Lachmann. “Further studies are warranted to examine the potential mechanisms of this association, to ultimately help in the development of potential strategies for prevention.”

In 2015, the American Society of Anesthesiologists launched a patient safety initiative—the Brain Health Initiative—to provide physician anesthesiologists and other clinicians involved in perioperative care, as well as patients and their families caring for older surgical patients, with the tools and resources necessary to optimize the cognitive recovery and perioperative experience for adults age 65 and older undergoing surgery.

Ketamine May Help Treat Medically Refractory Migraine Pain

Ketamine, a medication commonly used for pain relief and increasingly used for depression, may help alleviate migraine pain in patients who have not been helped by other treatments, a study suggests.

The trial of 61 patients found that almost 75% had an improvement in their migraine intensity after a three- to seven-day course of inpatient treatment with ketamine. The drug is used to induce general anesthesia, but also provides powerful pain control for patients with many painful conditions in lower doses than its anesthetic use.

“Ketamine may hold promise as a treatment for migraine headaches in patients who have failed other treatments,” said study coauthor Eric Schwenk, MD, Director of Orthopedic Anesthesia at Thomas Jefferson University Hospital in Philadelphia. “Our study focused only on short-term relief, but it is encouraging that this treatment might have the potential to help patients [in the] long-term. Our work provides the basis for future prospective studies that involve larger numbers of patients.”

An estimated 12% of the US population has migraines. A subset of these patients, along with those who have other types of headaches, does not respond to treatment. During a migraine, people are often sensitive to light and sound and may become nauseated or vomit. Migraines are three times more common in women than in men.

The researchers reviewed data for patients who received ketamine infusions for intractable migraine headaches—migraines that had failed all other therapies. On a scale of 0 to 10, the average migraine headache pain rating at admission was 7.5, compared with 3.4 at discharge. The average length of infusion was 5.1 days, and the day of lowest pain ratings was day 4. Adverse effects were generally mild.

Dr. Schwenk said that while his hospital uses ketamine to treat intractable migraines, the treatment is not yet widely available. Thomas Jefferson University Hospital will open a new infusion center that will treat more patients with headaches using ketamine. “We hope to expand its use to both more patients and more conditions in the future,” he said.

“Due to the retrospective nature of the study, we cannot definitively say that ketamine is entirely responsible for the pain relief, but we have provided a basis for additional larger studies to be undertaken,” Dr. Schwenk added.

Opioid Abuse Plateaus at a High Level

Although the rapid increase in opioid abuse has leveled off, the prevalence of abuse remains high and does not appear to be declining, according to an analysis of national data.

More than 13% of Americans age 12 and older—nearly one in seven—have abused prescription opioids at some point in their lives, researchers determined after analyzing the latest data from the National Survey on Drug Use and Health (NSDUH), an annual survey sponsored by the Substance Abuse and Mental Health Services Administration. Additionally, while 8.6% of Americans abused opioids in 2000, by 2003 that number increased to 13.2%, and it has remained at that level since.

“The amount of opioid prescriptions being written in the United States is breathtaking—essentially enough for every American adult to have a bottle of the pain killers in their medicine cabinet,” said Asokumar Buvanendran, MD, lead author of the study, Director of Orthopedic Anesthesia and Vice Chair for Research at Rush Medical College in Chicago, and chair of the American Society of Anesthesiologists (ASA) Committee on Pain Medicine. “This in turn leads to opioid abuse because people may take more than needed, or the pills fall into the wrong hands. That has got to change.”

Because opioids can produce euphoria, they are highly likely to be abused. Opioid prescriptions are often written for an excessive number of pills, so patients may take more medication than they need and become addicted. Additionally, unused medication can be diverted to another person for illicit use. More than half of the people who misuse prescribed opioids get them from a friend or relative, not a physician, according to NSDUH data.

The NSDUH survey asked Americans whether they had taken prescription opioids without a prescription written for them (which constitutes abuse) anytime in their lives. The researchers determined that in 2014 (the last year for which data was available), 13.6% of Americans had abused prescription opioids. Use of hydrocodone (including Vicodin, a combination of hydrocodone and acetaminophen) increased from 3.2% in 2000 to 9.1% in 2014. Use of oxycontin increased from less than 1% in 2000 to 3% in 2014.

Hydrocodone is the most frequently prescribed and therefore the most frequently abused opioid, researchers noted.

“While the illicit opioid use trend seems to have plateaued, there is no evidence of a decline yet,” said Mario Moric, coauthor of the study and a biostatistician at Rush Medical College. “Hopefully, with increased national attention to the problem we will see a significant drop in abuse.”

“Opioids are still an important tool for dealing with pain, but doctors need to prescribe smaller quantities,” said Dr. Buvanendran. “Also, patients need to be educated about the dangers of overuse and abuse and understand that pain usually cannot be solved solely with a pill, but needs to include exercise, physical therapy, eating right, having a social support system, and developing good coping skills.”

The ASA is committed to ending opioid abuse and has launched several initiatives to combat the epidemic.

Botox May Benefit Children With Hard-to-Treat Migraines

Injections of botulinum toxin (Botox) may provide significant relief for children with migraine headaches that do not respond to traditional treatment, suggests a small preliminary study.

Botox is approved by the FDA to treat migraines in adults. One in 10 school-aged children and teens have migraines, but there are few FDA-approved medications for this age group. Some children and teens do not respond well to available options, such as certain migraine rescue pain medications, and the pain and disability of migraines can have a severe impact on their lives. Preventative medications may help sometimes. Only one preventative migraine medication, topiramate, is approved for adolescents, however.

“When children and teens have migraine pain, it can severely affect their lives and ability to function. They miss school, their grades suffer, and they are left behind, often unable to reach their full potential. Clearly, there is a need for an alternative treatment for those who have not found relief,” said Shalini Shah, MD, lead author of the study and Chief of the Division of Pain Medicine at the University of California, Irvine. “After treatment, we saw improvement in functional aspects in all of the children and teens. In fact, one patient was hospitalized monthly for her migraine pain prior to Botox treatment and was expected to be held back in school. After treatment, she only has one or two migraines a year, and is excelling in college.”

The study included nine children and teens (ages 8 to 17) who had migraines on eight to 29.5 days per month. Most participants had tried numerous medications and other therapies without much relief. All received Botox injections in the front and back of the head and neck every 12 weeks and were evaluated during a five-year period. After treatment, the patients had migraines on two to 10 days per month.

In addition, when treated participants did have migraines, their headaches did not last as long. Patients’ migraines lasted from 30 minutes to 24 hours before treatment, and 15 minutes to seven hours after treatment. Their headaches also were not as painful. Patient-reported pain on a scale of 1–10 (from no pain to worst pain imaginable) ranged from 4 to 8 before treatment and 1.75 to 5 after treatment.

Eight adverse events were reported during the study. Most resulted from pain at the injection site. No severe adverse events were reported.

If the results of the current study are confirmed, Botox could provide an alternative for patients without treatment options, said Dr. Shah. Her team is enrolling patients to study this treatment in a prospective, randomized, double-blinded trial to compare Botox with placebo.

“Many current migraine medications have side effects, including sedation, dry mouth, and confusion, which are not well-tolerated in children and teens,” said Dr. Shah. “Our research of Botox is part of an effort to find better treatments for children and teens with migraines so they can realize their full potential.”

The study authors received no funding from the manufacturer of Botox.

Diabetes Increases Risk of Cognitive Problems After Surgery

Older patients with diabetes may be at an 84% higher risk of developing postoperative cognitive dysfunction (POCD) than those who are not diabetic, new research suggests.

“With POCD, a patient’s mental ability declines after surgery, compared to their cognitive performance before surgery, resulting not only in increased complications and potential death, but also impairing the patient’s quality of life,” said Gunnar Lachmann, MD, Department of Anesthesiology and Operative Intensive Care Medicine, Charité—Universitätsmedizin Berlin. “POCD is increasingly recognized as a common complication after major surgery, affecting 10% to 13% of patients, with seniors being especially vulnerable.”

POCD is a major form of cognitive disturbance that can occur after anesthesia and surgery, but little is known about its potential risk factors. An association between diabetes and age-related cognitive impairment is well established, but the role diabetes has in the development of POCD is unknown.

In the study, researchers performed a secondary analysis of three studies, comprising 1,034 patients (481 who had cardiac surgery and 553 who had noncardiac surgery), to examine whether diabetes was a risk factor for POCD. Patients’ mean age was 66.4. Of the 1,034 participants, 18.6% had diabetes. The association of diabetes with risk of POCD was determined using logistic regression models at the longest patient follow-up period for each study, which was three or 12 months. Risk estimates were pooled across all three studies.

After adjusting for age, sex, surgery type, randomization, obesity, and hypertension, the researchers determined that diabetes was associated with an 84% higher risk of POCD. Patients age 65 or older were at particularly high risk.

“Our findings suggest that consideration of diabetes status may be helpful for the assessment of POCD risk among patients undergoing surgery,” said Dr. Lachmann. “Further studies are warranted to examine the potential mechanisms of this association, to ultimately help in the development of potential strategies for prevention.”

In 2015, the American Society of Anesthesiologists launched a patient safety initiative—the Brain Health Initiative—to provide physician anesthesiologists and other clinicians involved in perioperative care, as well as patients and their families caring for older surgical patients, with the tools and resources necessary to optimize the cognitive recovery and perioperative experience for adults age 65 and older undergoing surgery.

Epilepsy during pregnancy is associated with a moderately increased risk of adverse pregnancy, delivery, and perinatal outcomes, according to research published in the August issue of JAMA Neurology. The use of antiepileptic drugs (AEDs), however, is not associated with adverse outcomes, according to the researchers.

Information From National Registries

Data suggesting associations between AEDs and the risk of congenital malformations have received much attention in recent years. But population-based evidence about the association between maternal epilepsy itself and risks of adverse outcomes has been scarce.

Dr. Razaz and colleagues conducted a retrospective study of all singleton births in Sweden from 1997 through 2011. The investigators obtained information from the country’s Medical Birth Register, the National Patient Register, and the Prescribed Drug Registry. They included information about 1,429,652 pregnancies (869,947 mothers without epilepsy and 3,586 mothers with epilepsy). Mean age at first delivery for women with epilepsy was 31. Data on AED exposure were available for offspring born between July 1, 2005, and December 31, 2011. Lamotrigine and carbamazepine were the most commonly used AEDs.

Relative Risks

Pregnancies in women with epilepsy were associated with increased risks of pre-eclampsia (adjusted risk ratio [aRR], 1.24), infection (aRR, 1.85), placental abruption (aRR, 1.68), induction (aRR, 1.31), elective cesarean section (aRR, 1.58), and emergency cesarean section (aRR, 1.09), compared with pregnancies in women without epilepsy. After adjustment for potential confounders, neonates of women with epilepsy had significantly higher risks of stillbirth, being born small for gestational age, medically indicated and spontaneous preterm births, any and major congenital malformations, neonatal infections, asphyxia-related complications, low five-minute Apgar scores, and neonatal hypoglycemia and respiratory distress, compared with neonates of women without epilepsy.

Among women with epilepsy, the rate of pre-eclampsia was higher in those who received AEDs, compared with women who did not receive AEDs (aRR, 1.39). In the propensity score-adjusted analyses, however, increased risk of induced labor (aRR, 1.30) was the only pregnancy and delivery outcome significantly associated with use of AEDs.

Offspring of women exposed to AEDs had a higher frequency of major malformation (6.7% vs 4.7%), respiratory distress (6.0% vs 4.5%), and being small for gestational age (9.5% vs 6.9%) at birth, compared with nonexposed offspring. Propensity score-adjusted analyses, however, showed no significantly increased risk of adverse neonatal outcomes.

Women with epilepsy who receive AEDs during pregnancy “may receive extra surveillance ... from their clinicians that may have contributed to the comparable outcomes observed in our study,” said the researchers. The study results may improve counseling for pregnant women with epilepsy who contemplate discontinuing treatment.

—Erik Greb

Suggested Reading

Razaz N, Tomson T, Wikström AK, Cnattingius S. Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol. 2017;74(8):983-991.

Epilepsy during pregnancy is associated with a moderately increased risk of adverse pregnancy, delivery, and perinatal outcomes, according to research published in the August issue of JAMA Neurology. The use of antiepileptic drugs (AEDs), however, is not associated with adverse outcomes, according to the researchers.

Information From National Registries

Data suggesting associations between AEDs and the risk of congenital malformations have received much attention in recent years. But population-based evidence about the association between maternal epilepsy itself and risks of adverse outcomes has been scarce.

Dr. Razaz and colleagues conducted a retrospective study of all singleton births in Sweden from 1997 through 2011. The investigators obtained information from the country’s Medical Birth Register, the National Patient Register, and the Prescribed Drug Registry. They included information about 1,429,652 pregnancies (869,947 mothers without epilepsy and 3,586 mothers with epilepsy). Mean age at first delivery for women with epilepsy was 31. Data on AED exposure were available for offspring born between July 1, 2005, and December 31, 2011. Lamotrigine and carbamazepine were the most commonly used AEDs.

Relative Risks

Pregnancies in women with epilepsy were associated with increased risks of pre-eclampsia (adjusted risk ratio [aRR], 1.24), infection (aRR, 1.85), placental abruption (aRR, 1.68), induction (aRR, 1.31), elective cesarean section (aRR, 1.58), and emergency cesarean section (aRR, 1.09), compared with pregnancies in women without epilepsy. After adjustment for potential confounders, neonates of women with epilepsy had significantly higher risks of stillbirth, being born small for gestational age, medically indicated and spontaneous preterm births, any and major congenital malformations, neonatal infections, asphyxia-related complications, low five-minute Apgar scores, and neonatal hypoglycemia and respiratory distress, compared with neonates of women without epilepsy.

Among women with epilepsy, the rate of pre-eclampsia was higher in those who received AEDs, compared with women who did not receive AEDs (aRR, 1.39). In the propensity score-adjusted analyses, however, increased risk of induced labor (aRR, 1.30) was the only pregnancy and delivery outcome significantly associated with use of AEDs.

Offspring of women exposed to AEDs had a higher frequency of major malformation (6.7% vs 4.7%), respiratory distress (6.0% vs 4.5%), and being small for gestational age (9.5% vs 6.9%) at birth, compared with nonexposed offspring. Propensity score-adjusted analyses, however, showed no significantly increased risk of adverse neonatal outcomes.

Women with epilepsy who receive AEDs during pregnancy “may receive extra surveillance ... from their clinicians that may have contributed to the comparable outcomes observed in our study,” said the researchers. The study results may improve counseling for pregnant women with epilepsy who contemplate discontinuing treatment.

—Erik Greb

Suggested Reading

Razaz N, Tomson T, Wikström AK, Cnattingius S. Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol. 2017;74(8):983-991.

Epilepsy during pregnancy is associated with a moderately increased risk of adverse pregnancy, delivery, and perinatal outcomes, according to research published in the August issue of JAMA Neurology. The use of antiepileptic drugs (AEDs), however, is not associated with adverse outcomes, according to the researchers.

Information From National Registries

Data suggesting associations between AEDs and the risk of congenital malformations have received much attention in recent years. But population-based evidence about the association between maternal epilepsy itself and risks of adverse outcomes has been scarce.

Dr. Razaz and colleagues conducted a retrospective study of all singleton births in Sweden from 1997 through 2011. The investigators obtained information from the country’s Medical Birth Register, the National Patient Register, and the Prescribed Drug Registry. They included information about 1,429,652 pregnancies (869,947 mothers without epilepsy and 3,586 mothers with epilepsy). Mean age at first delivery for women with epilepsy was 31. Data on AED exposure were available for offspring born between July 1, 2005, and December 31, 2011. Lamotrigine and carbamazepine were the most commonly used AEDs.

Relative Risks

Pregnancies in women with epilepsy were associated with increased risks of pre-eclampsia (adjusted risk ratio [aRR], 1.24), infection (aRR, 1.85), placental abruption (aRR, 1.68), induction (aRR, 1.31), elective cesarean section (aRR, 1.58), and emergency cesarean section (aRR, 1.09), compared with pregnancies in women without epilepsy. After adjustment for potential confounders, neonates of women with epilepsy had significantly higher risks of stillbirth, being born small for gestational age, medically indicated and spontaneous preterm births, any and major congenital malformations, neonatal infections, asphyxia-related complications, low five-minute Apgar scores, and neonatal hypoglycemia and respiratory distress, compared with neonates of women without epilepsy.

Among women with epilepsy, the rate of pre-eclampsia was higher in those who received AEDs, compared with women who did not receive AEDs (aRR, 1.39). In the propensity score-adjusted analyses, however, increased risk of induced labor (aRR, 1.30) was the only pregnancy and delivery outcome significantly associated with use of AEDs.

Offspring of women exposed to AEDs had a higher frequency of major malformation (6.7% vs 4.7%), respiratory distress (6.0% vs 4.5%), and being small for gestational age (9.5% vs 6.9%) at birth, compared with nonexposed offspring. Propensity score-adjusted analyses, however, showed no significantly increased risk of adverse neonatal outcomes.

Women with epilepsy who receive AEDs during pregnancy “may receive extra surveillance ... from their clinicians that may have contributed to the comparable outcomes observed in our study,” said the researchers. The study results may improve counseling for pregnant women with epilepsy who contemplate discontinuing treatment.

—Erik Greb

Suggested Reading

Razaz N, Tomson T, Wikström AK, Cnattingius S. Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol. 2017;74(8):983-991.

WASHINGTON, DC—Patients with Parkinson’s disease may have serious comorbidities and complications that require emergency department visits and hospitalizations. “Only 4.5% of hospitalizations of patients with Parkinson’s disease are for management of primary Parkinson’s disease, and most hospitalizations are due to comorbidity or management of complications,” said Alka Mithal, MD, of the Institute of Clinical Outcomes Research and Education in Woodside, California, and colleagues, at the 2017 National Association of Specialty Pharmacy Annual Meeting.

Few studies have examined serious complications and comorbidities of Parkinson’s disease requiring hospitalization. To study emergency department visits and hospitalizations in patients with Parkinson’s disease, Dr. Mithal and colleagues examined the 2014 Nationwide Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS) databases.NEDS, a sample of US hospital-based emergency departments, is the largest all-payer emergency department database in the US. NIS, a stratified random sample of all US community hospitals, is the largest inpatient care database with information on all inpatient care, regardless of insurance status. The investigators calculated prevalence per 100,000 US population. Population data were taken from the US Census Bureau.

In 2014, there were 137.8 million all-cause emergency department visits in the US, with prevalence of 43,219 visits per 100,000 population. Parkinson’s disease accounted for 416,787 emergency department visits (131 visits per 100,000 population). Men accounted for 55% of the visits. Medicare paid for 85% of the visits, and Medicaid paid for 4% of the visits.

Of 272,450 hospitalizations in patients with Parkinson’s disease, approximately 4.5% were directly related to a primary diagnosis of Parkinson’s disease. Men accounted for 57% of hospitalizations (prevalence of 129/100,000 in men older than 18, and 94/100,000 in women older than 18). The average charges per hospitalization were $47,006, with a mean length of stay of 3.8 days. Medicare paid for 87% of these hospitalizations.

In a separate study, Dr. Mithal and colleagues used the 2014 NIS to examine hospitalizations in patients younger than 65 with a diagnosis of Parkinson’s disease. There were 33,650 such hospitalizations (60% men). The mean length of hospitalization was 5.96 days. “Parkinson’s disease and its complications are not limited to the elderly,” the researchers said. “Patients younger than 65 … accounted for over $1.7 billion in hospitalization expenses alone in 2014.”

Acorda Therapeutics funded the studies.

WASHINGTON, DC—Patients with Parkinson’s disease may have serious comorbidities and complications that require emergency department visits and hospitalizations. “Only 4.5% of hospitalizations of patients with Parkinson’s disease are for management of primary Parkinson’s disease, and most hospitalizations are due to comorbidity or management of complications,” said Alka Mithal, MD, of the Institute of Clinical Outcomes Research and Education in Woodside, California, and colleagues, at the 2017 National Association of Specialty Pharmacy Annual Meeting.

Few studies have examined serious complications and comorbidities of Parkinson’s disease requiring hospitalization. To study emergency department visits and hospitalizations in patients with Parkinson’s disease, Dr. Mithal and colleagues examined the 2014 Nationwide Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS) databases.NEDS, a sample of US hospital-based emergency departments, is the largest all-payer emergency department database in the US. NIS, a stratified random sample of all US community hospitals, is the largest inpatient care database with information on all inpatient care, regardless of insurance status. The investigators calculated prevalence per 100,000 US population. Population data were taken from the US Census Bureau.

In 2014, there were 137.8 million all-cause emergency department visits in the US, with prevalence of 43,219 visits per 100,000 population. Parkinson’s disease accounted for 416,787 emergency department visits (131 visits per 100,000 population). Men accounted for 55% of the visits. Medicare paid for 85% of the visits, and Medicaid paid for 4% of the visits.

Of 272,450 hospitalizations in patients with Parkinson’s disease, approximately 4.5% were directly related to a primary diagnosis of Parkinson’s disease. Men accounted for 57% of hospitalizations (prevalence of 129/100,000 in men older than 18, and 94/100,000 in women older than 18). The average charges per hospitalization were $47,006, with a mean length of stay of 3.8 days. Medicare paid for 87% of these hospitalizations.

In a separate study, Dr. Mithal and colleagues used the 2014 NIS to examine hospitalizations in patients younger than 65 with a diagnosis of Parkinson’s disease. There were 33,650 such hospitalizations (60% men). The mean length of hospitalization was 5.96 days. “Parkinson’s disease and its complications are not limited to the elderly,” the researchers said. “Patients younger than 65 … accounted for over $1.7 billion in hospitalization expenses alone in 2014.”

Acorda Therapeutics funded the studies.

WASHINGTON, DC—Patients with Parkinson’s disease may have serious comorbidities and complications that require emergency department visits and hospitalizations. “Only 4.5% of hospitalizations of patients with Parkinson’s disease are for management of primary Parkinson’s disease, and most hospitalizations are due to comorbidity or management of complications,” said Alka Mithal, MD, of the Institute of Clinical Outcomes Research and Education in Woodside, California, and colleagues, at the 2017 National Association of Specialty Pharmacy Annual Meeting.

Few studies have examined serious complications and comorbidities of Parkinson’s disease requiring hospitalization. To study emergency department visits and hospitalizations in patients with Parkinson’s disease, Dr. Mithal and colleagues examined the 2014 Nationwide Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS) databases.NEDS, a sample of US hospital-based emergency departments, is the largest all-payer emergency department database in the US. NIS, a stratified random sample of all US community hospitals, is the largest inpatient care database with information on all inpatient care, regardless of insurance status. The investigators calculated prevalence per 100,000 US population. Population data were taken from the US Census Bureau.

In 2014, there were 137.8 million all-cause emergency department visits in the US, with prevalence of 43,219 visits per 100,000 population. Parkinson’s disease accounted for 416,787 emergency department visits (131 visits per 100,000 population). Men accounted for 55% of the visits. Medicare paid for 85% of the visits, and Medicaid paid for 4% of the visits.

Of 272,450 hospitalizations in patients with Parkinson’s disease, approximately 4.5% were directly related to a primary diagnosis of Parkinson’s disease. Men accounted for 57% of hospitalizations (prevalence of 129/100,000 in men older than 18, and 94/100,000 in women older than 18). The average charges per hospitalization were $47,006, with a mean length of stay of 3.8 days. Medicare paid for 87% of these hospitalizations.

In a separate study, Dr. Mithal and colleagues used the 2014 NIS to examine hospitalizations in patients younger than 65 with a diagnosis of Parkinson’s disease. There were 33,650 such hospitalizations (60% men). The mean length of hospitalization was 5.96 days. “Parkinson’s disease and its complications are not limited to the elderly,” the researchers said. “Patients younger than 65 … accounted for over $1.7 billion in hospitalization expenses alone in 2014.”

Acorda Therapeutics funded the studies.

SAN DIEGO – Multiple doses of the investigational agent CFZ533 administered for 24 weeks in patients with primary Sjögren’s syndrome were safe and well tolerated, according to results of a proof-of-concept study.

CFZ533 is a novel monoclonal antibody being developed by Novartis that potently and selectively blocks CD40, a costimulatory pathway receptor essential for germinal center reactions and other immune-mediated functions implicated in primary Sjögren’s syndrome pathogenesis.

“Sjögren’s syndrome is characterized by focal infiltration of lymphocytes in a periductal distribution in exocrine glands,” lead study author Benjamin Fisher, MD, said at the annual meeting of the American College of Rheumatology.

“These lymphocytic foci often show organization and a proportion will show a germinal center formation. The lymphocytic infiltrates are associated with profound dryness, conjunctival erosions, fatigue that’s disabling, and in at least one-third of patients, systemic manifestations. There are no proven immunomodulatory treatments for this Sjögren’s syndrome. The lymphocytic infiltrates are also characterized by the expression of the costimulatory molecule CD40 and its ligand, also known as CD154,” he said.

[email protected]

SAN DIEGO – Multiple doses of the investigational agent CFZ533 administered for 24 weeks in patients with primary Sjögren’s syndrome were safe and well tolerated, according to results of a proof-of-concept study.

CFZ533 is a novel monoclonal antibody being developed by Novartis that potently and selectively blocks CD40, a costimulatory pathway receptor essential for germinal center reactions and other immune-mediated functions implicated in primary Sjögren’s syndrome pathogenesis.

“Sjögren’s syndrome is characterized by focal infiltration of lymphocytes in a periductal distribution in exocrine glands,” lead study author Benjamin Fisher, MD, said at the annual meeting of the American College of Rheumatology.

“These lymphocytic foci often show organization and a proportion will show a germinal center formation. The lymphocytic infiltrates are associated with profound dryness, conjunctival erosions, fatigue that’s disabling, and in at least one-third of patients, systemic manifestations. There are no proven immunomodulatory treatments for this Sjögren’s syndrome. The lymphocytic infiltrates are also characterized by the expression of the costimulatory molecule CD40 and its ligand, also known as CD154,” he said.

[email protected]

SAN DIEGO – Multiple doses of the investigational agent CFZ533 administered for 24 weeks in patients with primary Sjögren’s syndrome were safe and well tolerated, according to results of a proof-of-concept study.

CFZ533 is a novel monoclonal antibody being developed by Novartis that potently and selectively blocks CD40, a costimulatory pathway receptor essential for germinal center reactions and other immune-mediated functions implicated in primary Sjögren’s syndrome pathogenesis.

“Sjögren’s syndrome is characterized by focal infiltration of lymphocytes in a periductal distribution in exocrine glands,” lead study author Benjamin Fisher, MD, said at the annual meeting of the American College of Rheumatology.

“These lymphocytic foci often show organization and a proportion will show a germinal center formation. The lymphocytic infiltrates are associated with profound dryness, conjunctival erosions, fatigue that’s disabling, and in at least one-third of patients, systemic manifestations. There are no proven immunomodulatory treatments for this Sjögren’s syndrome. The lymphocytic infiltrates are also characterized by the expression of the costimulatory molecule CD40 and its ligand, also known as CD154,” he said.

[email protected]

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Current treatment with available light-based devices, notably ablative fractional resurfacing, can greatly improve quality of life for patients struggling with scars, according to Kristen Kelly, MD, of the University of California, Irvine.

Using multiple devices, and combining devices with other therapies, are among the strategies that can improve pain and function in these patients, she said in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

[email protected]

Current treatment with available light-based devices, notably ablative fractional resurfacing, can greatly improve quality of life for patients struggling with scars, according to Kristen Kelly, MD, of the University of California, Irvine.

Using multiple devices, and combining devices with other therapies, are among the strategies that can improve pain and function in these patients, she said in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

[email protected]

Current treatment with available light-based devices, notably ablative fractional resurfacing, can greatly improve quality of life for patients struggling with scars, according to Kristen Kelly, MD, of the University of California, Irvine.

Using multiple devices, and combining devices with other therapies, are among the strategies that can improve pain and function in these patients, she said in a presentation at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

[email protected]

Discharging patients with low-risk pulmonary embolism (PE) sooner not only saves money, but it could be saving their lives, according to a study of 6,746 VHA patients with PE.

Of the patients, 1,918 were low-risk, and of those, 688 had a short length of stay (LOS) (2 days or less). While adverse events associated with PE (recurrent venous thromboembolism, major bleeding, and death) were similar, patients with short LOS had fewer hospital-acquired complications (1.5% vs 13.3%) and bacterial pneumonias (5.9% vs 11.7%). Patients in the long LOS cohort had a higher number of pharmacy visits per patient (12.2 vs 9.4) and surgeries for placement of the inferior vena cava filter.

The researchers note that PE is associated with a “substantial burden” of health care utilization and associated costs. The annual cost per patient for an initial episode of PE ranges from $13,000 to $31,000; with recurrent episodes, the cost can be $11,014-$14,722 per year. In this study, inpatient costs for short LOS were half those of the longer LOS costs ($2,164 vs $5,100). Total costs were $9,056 for short LOS vs $12,544.

But they also note that since patients with low-risk PE can be identified using the validated risk stratification tools, an opportunity exists to select patients who can be safely treated without a traditional hospital admission. The researchers cite estimates that, in fact, up to 50% of PE patients can be treated safely as outpatients. Although this is common practice in Europe, U.S. physicians have been less willing to adopt the strategy, they add.

Risk stratification, the researchers conclude, is “of utmost importance”: Reducing the LOS among low-risk PE patients may substantially reduce the disease’s clinical and economic burden.

Discharging patients with low-risk pulmonary embolism (PE) sooner not only saves money, but it could be saving their lives, according to a study of 6,746 VHA patients with PE.

Of the patients, 1,918 were low-risk, and of those, 688 had a short length of stay (LOS) (2 days or less). While adverse events associated with PE (recurrent venous thromboembolism, major bleeding, and death) were similar, patients with short LOS had fewer hospital-acquired complications (1.5% vs 13.3%) and bacterial pneumonias (5.9% vs 11.7%). Patients in the long LOS cohort had a higher number of pharmacy visits per patient (12.2 vs 9.4) and surgeries for placement of the inferior vena cava filter.

The researchers note that PE is associated with a “substantial burden” of health care utilization and associated costs. The annual cost per patient for an initial episode of PE ranges from $13,000 to $31,000; with recurrent episodes, the cost can be $11,014-$14,722 per year. In this study, inpatient costs for short LOS were half those of the longer LOS costs ($2,164 vs $5,100). Total costs were $9,056 for short LOS vs $12,544.

But they also note that since patients with low-risk PE can be identified using the validated risk stratification tools, an opportunity exists to select patients who can be safely treated without a traditional hospital admission. The researchers cite estimates that, in fact, up to 50% of PE patients can be treated safely as outpatients. Although this is common practice in Europe, U.S. physicians have been less willing to adopt the strategy, they add.

Risk stratification, the researchers conclude, is “of utmost importance”: Reducing the LOS among low-risk PE patients may substantially reduce the disease’s clinical and economic burden.

Discharging patients with low-risk pulmonary embolism (PE) sooner not only saves money, but it could be saving their lives, according to a study of 6,746 VHA patients with PE.

Of the patients, 1,918 were low-risk, and of those, 688 had a short length of stay (LOS) (2 days or less). While adverse events associated with PE (recurrent venous thromboembolism, major bleeding, and death) were similar, patients with short LOS had fewer hospital-acquired complications (1.5% vs 13.3%) and bacterial pneumonias (5.9% vs 11.7%). Patients in the long LOS cohort had a higher number of pharmacy visits per patient (12.2 vs 9.4) and surgeries for placement of the inferior vena cava filter.

The researchers note that PE is associated with a “substantial burden” of health care utilization and associated costs. The annual cost per patient for an initial episode of PE ranges from $13,000 to $31,000; with recurrent episodes, the cost can be $11,014-$14,722 per year. In this study, inpatient costs for short LOS were half those of the longer LOS costs ($2,164 vs $5,100). Total costs were $9,056 for short LOS vs $12,544.

But they also note that since patients with low-risk PE can be identified using the validated risk stratification tools, an opportunity exists to select patients who can be safely treated without a traditional hospital admission. The researchers cite estimates that, in fact, up to 50% of PE patients can be treated safely as outpatients. Although this is common practice in Europe, U.S. physicians have been less willing to adopt the strategy, they add.

Risk stratification, the researchers conclude, is “of utmost importance”: Reducing the LOS among low-risk PE patients may substantially reduce the disease’s clinical and economic burden.

Augusta University

New research has shown an increased risk of early death in patients with acute myeloid leukemia (AML) who have high levels of indoleamine 2,3 dioxygenase-1 (IDO-1), an enzyme known to suppress the immune system.

Researchers quantified IDO-1 expression in diagnostic samples from patients with AML and discovered that high levels of IDO-1 were significantly associated with induction failure and poor overall survival (OS).

Ravindra Kolhe, MD, PhD, of the Medical College of Georgia at Augusta University, and his colleagues recounted these findings in Scientific Reports.

The researchers reviewed data from 40 AML patients. They had a median age at diagnosis of 60 (range, 27–89), 60% were female, and 55% were self-reported as Caucasian.

Most patients (72.5%) received standard anthracycline and cytarabine as induction, 10% received hypomethylating agents, and 17.5% were untreated or had unknown treatment status.

Fifteen percent of patients underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) at the time of first complete remission.

Half of all patients achieved remission, and half of those patients (n=10, 25%) had a subsequent relapse. The median OS was 283 days (range, 32–1941). Twenty percent of patients (n=8) were still alive at the time of data analysis.

IDO-1 analysis

“We wanted to look at what makes this leukemia so aggressive that initial induction chemotherapy is not working,” Dr Kolhe said. “Early relapse tends to predict early mortality in these patients, and one of the things we looked at was IDO.”

The researchers extracted IDO-1 mRNA from diagnostic bone marrow samples from 29 of the patients but assessed IDO-1 protein expression in all 40 patients via immunohistochemistry.

The team quantified IDO-1 expression using a “composite IDO-1 score.” They used a cut-off point of 0.45 and divided patients’ samples into 2 groups: high (≥0.45) and low (<0.45) IDO-1 score.

The researchers compared IDO-1 results across 4 survival groups, which included patients surviving:

• Less than 6 months
• More than 6 months to 1 year
• More than 1 year to less than 5 years
• Beyond 5 years.

The team found a direct correlation between poor OS and higher composite IDO-1 score (P=0.0005).

“The patients who died at 6 months had a high expression of IDO, while the blasts produced relatively little IDO in the patients who lived 5 years or more,” Dr Kolhe said.

Independent predictor

The researchers conducted a univariate analysis and identified several factors that were significantly associated with poor OS, including:

• Higher IDO-1 mRNA (P=0.005)
• Higher composite IDO-1 score (P<0.0001)
• Higher age (P=0.0018)
• Male gender (P=0.019)
• High-risk cytogenetics (P=0.002)
• Not undergoing allo-HSCT (P=0.0005).

In a multivariate analysis including the above variables, the researchers found that a higher composite IDO-1 score (P=0.007) and not undergoing allo-HSCT (P=0.007) were significantly associated with poor OS.

The team also found that patients who failed induction had a higher composite IDO-1 score (P=0.01).

“Most of the time, we don’t know why patients are not responding to chemotherapy,” Dr Kolhe noted. “But when the researchers adjusted for other risk factors for AML, like increased age and severe anemia, IDO levels were a standout. Right now, we know it’s high in patients who die at 6 months, and we show that it’s an independent indicator if you adjust for other known variables.”

Dr Kolhe said these results suggest IDO-1 expression should be measured when the diagnostic bone marrow biopsy is performed. This may help identify AML patients who could benefit from receiving an IDO inhibitor along with standard therapy.

Researchers are currently conducting a phase 1/2 trial of the IDO inhibitor indoximod in combination with idarubicin and cytarabine in patients with newly diagnosed AML (NCT02835729).

Augusta University

New research has shown an increased risk of early death in patients with acute myeloid leukemia (AML) who have high levels of indoleamine 2,3 dioxygenase-1 (IDO-1), an enzyme known to suppress the immune system.

Researchers quantified IDO-1 expression in diagnostic samples from patients with AML and discovered that high levels of IDO-1 were significantly associated with induction failure and poor overall survival (OS).

Ravindra Kolhe, MD, PhD, of the Medical College of Georgia at Augusta University, and his colleagues recounted these findings in Scientific Reports.

The researchers reviewed data from 40 AML patients. They had a median age at diagnosis of 60 (range, 27–89), 60% were female, and 55% were self-reported as Caucasian.

Most patients (72.5%) received standard anthracycline and cytarabine as induction, 10% received hypomethylating agents, and 17.5% were untreated or had unknown treatment status.

Fifteen percent of patients underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) at the time of first complete remission.

Half of all patients achieved remission, and half of those patients (n=10, 25%) had a subsequent relapse. The median OS was 283 days (range, 32–1941). Twenty percent of patients (n=8) were still alive at the time of data analysis.

IDO-1 analysis

“We wanted to look at what makes this leukemia so aggressive that initial induction chemotherapy is not working,” Dr Kolhe said. “Early relapse tends to predict early mortality in these patients, and one of the things we looked at was IDO.”

The researchers extracted IDO-1 mRNA from diagnostic bone marrow samples from 29 of the patients but assessed IDO-1 protein expression in all 40 patients via immunohistochemistry.

The team quantified IDO-1 expression using a “composite IDO-1 score.” They used a cut-off point of 0.45 and divided patients’ samples into 2 groups: high (≥0.45) and low (<0.45) IDO-1 score.

The researchers compared IDO-1 results across 4 survival groups, which included patients surviving:

• Less than 6 months
• More than 6 months to 1 year
• More than 1 year to less than 5 years
• Beyond 5 years.

The team found a direct correlation between poor OS and higher composite IDO-1 score (P=0.0005).

“The patients who died at 6 months had a high expression of IDO, while the blasts produced relatively little IDO in the patients who lived 5 years or more,” Dr Kolhe said.

Independent predictor

The researchers conducted a univariate analysis and identified several factors that were significantly associated with poor OS, including:

• Higher IDO-1 mRNA (P=0.005)
• Higher composite IDO-1 score (P<0.0001)
• Higher age (P=0.0018)
• Male gender (P=0.019)
• High-risk cytogenetics (P=0.002)
• Not undergoing allo-HSCT (P=0.0005).

In a multivariate analysis including the above variables, the researchers found that a higher composite IDO-1 score (P=0.007) and not undergoing allo-HSCT (P=0.007) were significantly associated with poor OS.

The team also found that patients who failed induction had a higher composite IDO-1 score (P=0.01).

“Most of the time, we don’t know why patients are not responding to chemotherapy,” Dr Kolhe noted. “But when the researchers adjusted for other risk factors for AML, like increased age and severe anemia, IDO levels were a standout. Right now, we know it’s high in patients who die at 6 months, and we show that it’s an independent indicator if you adjust for other known variables.”

Dr Kolhe said these results suggest IDO-1 expression should be measured when the diagnostic bone marrow biopsy is performed. This may help identify AML patients who could benefit from receiving an IDO inhibitor along with standard therapy.

Researchers are currently conducting a phase 1/2 trial of the IDO inhibitor indoximod in combination with idarubicin and cytarabine in patients with newly diagnosed AML (NCT02835729).

Augusta University

New research has shown an increased risk of early death in patients with acute myeloid leukemia (AML) who have high levels of indoleamine 2,3 dioxygenase-1 (IDO-1), an enzyme known to suppress the immune system.

Researchers quantified IDO-1 expression in diagnostic samples from patients with AML and discovered that high levels of IDO-1 were significantly associated with induction failure and poor overall survival (OS).

Ravindra Kolhe, MD, PhD, of the Medical College of Georgia at Augusta University, and his colleagues recounted these findings in Scientific Reports.

The researchers reviewed data from 40 AML patients. They had a median age at diagnosis of 60 (range, 27–89), 60% were female, and 55% were self-reported as Caucasian.

Most patients (72.5%) received standard anthracycline and cytarabine as induction, 10% received hypomethylating agents, and 17.5% were untreated or had unknown treatment status.

Fifteen percent of patients underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) at the time of first complete remission.

Half of all patients achieved remission, and half of those patients (n=10, 25%) had a subsequent relapse. The median OS was 283 days (range, 32–1941). Twenty percent of patients (n=8) were still alive at the time of data analysis.

IDO-1 analysis

“We wanted to look at what makes this leukemia so aggressive that initial induction chemotherapy is not working,” Dr Kolhe said. “Early relapse tends to predict early mortality in these patients, and one of the things we looked at was IDO.”

The researchers extracted IDO-1 mRNA from diagnostic bone marrow samples from 29 of the patients but assessed IDO-1 protein expression in all 40 patients via immunohistochemistry.

The team quantified IDO-1 expression using a “composite IDO-1 score.” They used a cut-off point of 0.45 and divided patients’ samples into 2 groups: high (≥0.45) and low (<0.45) IDO-1 score.

The researchers compared IDO-1 results across 4 survival groups, which included patients surviving:

• Less than 6 months
• More than 6 months to 1 year
• More than 1 year to less than 5 years
• Beyond 5 years.

The team found a direct correlation between poor OS and higher composite IDO-1 score (P=0.0005).

“The patients who died at 6 months had a high expression of IDO, while the blasts produced relatively little IDO in the patients who lived 5 years or more,” Dr Kolhe said.

Independent predictor

The researchers conducted a univariate analysis and identified several factors that were significantly associated with poor OS, including:

• Higher IDO-1 mRNA (P=0.005)
• Higher composite IDO-1 score (P<0.0001)
• Higher age (P=0.0018)
• Male gender (P=0.019)
• High-risk cytogenetics (P=0.002)
• Not undergoing allo-HSCT (P=0.0005).

In a multivariate analysis including the above variables, the researchers found that a higher composite IDO-1 score (P=0.007) and not undergoing allo-HSCT (P=0.007) were significantly associated with poor OS.

The team also found that patients who failed induction had a higher composite IDO-1 score (P=0.01).

“Most of the time, we don’t know why patients are not responding to chemotherapy,” Dr Kolhe noted. “But when the researchers adjusted for other risk factors for AML, like increased age and severe anemia, IDO levels were a standout. Right now, we know it’s high in patients who die at 6 months, and we show that it’s an independent indicator if you adjust for other known variables.”

Dr Kolhe said these results suggest IDO-1 expression should be measured when the diagnostic bone marrow biopsy is performed. This may help identify AML patients who could benefit from receiving an IDO inhibitor along with standard therapy.

Researchers are currently conducting a phase 1/2 trial of the IDO inhibitor indoximod in combination with idarubicin and cytarabine in patients with newly diagnosed AML (NCT02835729).

Photo from iStock

Results of a small study suggest that negative thoughts and emotions may increase opioid use in patients with sickle cell disease (SCD).

Researchers analyzed data from daily electronic patient diaries and found that patients were more likely to use short-acting opioids both when they experienced increased pain and “catastrophic” thoughts about that pain.

In fact, pain catastrophizing led to an increased use of short-acting opioids even when patients reported low levels of pain.

In addition, patients were more likely to use long-acting opioids when they experienced negative emotions.

The researchers noted that this study wasn’t designed to show that negative emotions or thinking cause an increase in opioid use. It was only designed to determine if there was an association.

Patrick Finan, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this study in The Journal of Pain.

The researchers enrolled 85 adults with SCD in this study. Patients were asked to fill out electronic diaries on a handheld personal computer every evening for 90 days.

The final analysis included only 45 patients, as these were the subjects who filled out the diary more than 25% of the time and had taken opioid pills at least once during the study period.

The patients had an average age of 37, and 71% were female. Most (93%) were African American, and 7% were classified as “other” or did not report their race.

At the start of the study, the patients reported on the dosage and type of opioid pill they were prescribed for long-acting and short-acting use. The daily diary collected data on the number of long-acting and short-acting opioid pills taken per day.

Patients rated their daily pain level on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable.

Patients also rated positive emotions—including happy, calm, and cheerful—and negative emotions—including lonely, sad, anxious, and tired—on a scale of 0 to 10, with 0 being no emotion and 10 being the most intense emotion. The scores were converted to a 0-to-100 scale for the data analysis.

Separately, the researchers measured negative thinking using a Pain Catastrophizing Scale to rate “rumination,” or focus on pain, helplessness, and magnification of a current pain situation.

Results

Negative emotions were significantly associated with increased levels of long-acting opioids (P=0.001). The opioid dosage increased by 3.4 morphine milligram equivalents for every 10-point increase in negative emotions.

On the other hand, patients’ daily pain level, positive emotions, and negative thinking through catastrophizing did not significantly affect the amount of long-acting opioids taken.

“When someone is prescribed a daily, long-acting opioid, it is typically supposed to be at a fixed dose, and their pain level or emotions shouldn’t dictate whether they take more of this prescription or not,” Dr Finan said.

“Although we can’t prove misuse of the medication in our study, these data suggest that physicians and patients should clearly communicate about how patients should be taking their daily, long-acting opioids in order to minimize the potential for misuse.”

The researchers also found a significant association with short-acting opioid use and daily pain levels (P=0.006) as well as negative thinking by catastrophizing (P<0.001).

For every 10-point increase on the pain scale, the amount of short-acting opioids increased by 1.8 morphine milligram equivalents, and for every 10-point increase on the catastrophizing scale, pain medicine dosage increased by 2.5 morphine milligram equivalents.

Positive and negative emotions had no significant effect on the use of short-acting opioids.

“When pain was reported as low, sickle cell disease patients reported higher opioid use if they catastrophized, or focused their thinking on their pain, than if they didn’t,” Dr Finan said. “When pain levels were higher, negative thinking played less of a role in influencing opioid use.”

Dr Finan cautioned that studies such as this have some weaknesses, including the fact that self-reports are always uncertain, and the study only included 1 time point per day, although a person’s mood may fluctuate throughout the day based on life events and experiences.

For future studies, Dr Finan wants to use smartphone technology that can assess moods randomly throughout the day.

“Once we have a more intensive study to track mood variations throughout the day,” Dr Finan said, “then we can determine when it will be appropriate to send messages through text to intervene and affect patient behavior.”

Photo from iStock

Results of a small study suggest that negative thoughts and emotions may increase opioid use in patients with sickle cell disease (SCD).

Researchers analyzed data from daily electronic patient diaries and found that patients were more likely to use short-acting opioids both when they experienced increased pain and “catastrophic” thoughts about that pain.

In fact, pain catastrophizing led to an increased use of short-acting opioids even when patients reported low levels of pain.

In addition, patients were more likely to use long-acting opioids when they experienced negative emotions.

The researchers noted that this study wasn’t designed to show that negative emotions or thinking cause an increase in opioid use. It was only designed to determine if there was an association.

Patrick Finan, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this study in The Journal of Pain.

The researchers enrolled 85 adults with SCD in this study. Patients were asked to fill out electronic diaries on a handheld personal computer every evening for 90 days.

The final analysis included only 45 patients, as these were the subjects who filled out the diary more than 25% of the time and had taken opioid pills at least once during the study period.

The patients had an average age of 37, and 71% were female. Most (93%) were African American, and 7% were classified as “other” or did not report their race.

At the start of the study, the patients reported on the dosage and type of opioid pill they were prescribed for long-acting and short-acting use. The daily diary collected data on the number of long-acting and short-acting opioid pills taken per day.

Patients rated their daily pain level on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable.

Patients also rated positive emotions—including happy, calm, and cheerful—and negative emotions—including lonely, sad, anxious, and tired—on a scale of 0 to 10, with 0 being no emotion and 10 being the most intense emotion. The scores were converted to a 0-to-100 scale for the data analysis.

Separately, the researchers measured negative thinking using a Pain Catastrophizing Scale to rate “rumination,” or focus on pain, helplessness, and magnification of a current pain situation.

Results

Negative emotions were significantly associated with increased levels of long-acting opioids (P=0.001). The opioid dosage increased by 3.4 morphine milligram equivalents for every 10-point increase in negative emotions.

On the other hand, patients’ daily pain level, positive emotions, and negative thinking through catastrophizing did not significantly affect the amount of long-acting opioids taken.

“When someone is prescribed a daily, long-acting opioid, it is typically supposed to be at a fixed dose, and their pain level or emotions shouldn’t dictate whether they take more of this prescription or not,” Dr Finan said.

“Although we can’t prove misuse of the medication in our study, these data suggest that physicians and patients should clearly communicate about how patients should be taking their daily, long-acting opioids in order to minimize the potential for misuse.”

The researchers also found a significant association with short-acting opioid use and daily pain levels (P=0.006) as well as negative thinking by catastrophizing (P<0.001).

For every 10-point increase on the pain scale, the amount of short-acting opioids increased by 1.8 morphine milligram equivalents, and for every 10-point increase on the catastrophizing scale, pain medicine dosage increased by 2.5 morphine milligram equivalents.

Positive and negative emotions had no significant effect on the use of short-acting opioids.

“When pain was reported as low, sickle cell disease patients reported higher opioid use if they catastrophized, or focused their thinking on their pain, than if they didn’t,” Dr Finan said. “When pain levels were higher, negative thinking played less of a role in influencing opioid use.”

Dr Finan cautioned that studies such as this have some weaknesses, including the fact that self-reports are always uncertain, and the study only included 1 time point per day, although a person’s mood may fluctuate throughout the day based on life events and experiences.

For future studies, Dr Finan wants to use smartphone technology that can assess moods randomly throughout the day.

“Once we have a more intensive study to track mood variations throughout the day,” Dr Finan said, “then we can determine when it will be appropriate to send messages through text to intervene and affect patient behavior.”

Photo from iStock

Results of a small study suggest that negative thoughts and emotions may increase opioid use in patients with sickle cell disease (SCD).

Researchers analyzed data from daily electronic patient diaries and found that patients were more likely to use short-acting opioids both when they experienced increased pain and “catastrophic” thoughts about that pain.

In fact, pain catastrophizing led to an increased use of short-acting opioids even when patients reported low levels of pain.

In addition, patients were more likely to use long-acting opioids when they experienced negative emotions.

The researchers noted that this study wasn’t designed to show that negative emotions or thinking cause an increase in opioid use. It was only designed to determine if there was an association.

Patrick Finan, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described this study in The Journal of Pain.

The researchers enrolled 85 adults with SCD in this study. Patients were asked to fill out electronic diaries on a handheld personal computer every evening for 90 days.

The final analysis included only 45 patients, as these were the subjects who filled out the diary more than 25% of the time and had taken opioid pills at least once during the study period.

The patients had an average age of 37, and 71% were female. Most (93%) were African American, and 7% were classified as “other” or did not report their race.

At the start of the study, the patients reported on the dosage and type of opioid pill they were prescribed for long-acting and short-acting use. The daily diary collected data on the number of long-acting and short-acting opioid pills taken per day.

Patients rated their daily pain level on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable.

Patients also rated positive emotions—including happy, calm, and cheerful—and negative emotions—including lonely, sad, anxious, and tired—on a scale of 0 to 10, with 0 being no emotion and 10 being the most intense emotion. The scores were converted to a 0-to-100 scale for the data analysis.

Separately, the researchers measured negative thinking using a Pain Catastrophizing Scale to rate “rumination,” or focus on pain, helplessness, and magnification of a current pain situation.

Results

Negative emotions were significantly associated with increased levels of long-acting opioids (P=0.001). The opioid dosage increased by 3.4 morphine milligram equivalents for every 10-point increase in negative emotions.

On the other hand, patients’ daily pain level, positive emotions, and negative thinking through catastrophizing did not significantly affect the amount of long-acting opioids taken.

“When someone is prescribed a daily, long-acting opioid, it is typically supposed to be at a fixed dose, and their pain level or emotions shouldn’t dictate whether they take more of this prescription or not,” Dr Finan said.

“Although we can’t prove misuse of the medication in our study, these data suggest that physicians and patients should clearly communicate about how patients should be taking their daily, long-acting opioids in order to minimize the potential for misuse.”

The researchers also found a significant association with short-acting opioid use and daily pain levels (P=0.006) as well as negative thinking by catastrophizing (P<0.001).

For every 10-point increase on the pain scale, the amount of short-acting opioids increased by 1.8 morphine milligram equivalents, and for every 10-point increase on the catastrophizing scale, pain medicine dosage increased by 2.5 morphine milligram equivalents.

Positive and negative emotions had no significant effect on the use of short-acting opioids.

“When pain was reported as low, sickle cell disease patients reported higher opioid use if they catastrophized, or focused their thinking on their pain, than if they didn’t,” Dr Finan said. “When pain levels were higher, negative thinking played less of a role in influencing opioid use.”

Dr Finan cautioned that studies such as this have some weaknesses, including the fact that self-reports are always uncertain, and the study only included 1 time point per day, although a person’s mood may fluctuate throughout the day based on life events and experiences.

For future studies, Dr Finan wants to use smartphone technology that can assess moods randomly throughout the day.

“Once we have a more intensive study to track mood variations throughout the day,” Dr Finan said, “then we can determine when it will be appropriate to send messages through text to intervene and affect patient behavior.”

Photo from Georgia Tech

Although many scientific journals try to provide details about authors’ contributions to a publication by requiring explicit statements, contribution statements get much less attention than authorship order, according to research published in Science Advances.

Researchers surveyed more than 6000 corresponding authors of studies published in recent years and found they consider contribution statements helpful for understanding the specific skills individual authors bring to a study.

However, the respondents said they still use author order for deciphering which authors did how much of the work and deserve most of the credit.

“The lack of uniformity and detail in contribution statements leaves open the door for varied interpretations, which could be why only a minority of respondents found them more useful than author order,” said Henry Sauermann, PhD, of ESMT Berlin in Germany.

Dr Sauermann and his colleagues also examined the relationship between author order and contribution statements on more than 12,000 published articles.

The contribution statements studied did include information about the types of work contributed by each author. However, multiple authors could be listed under the same contributions, and the statements had little information about the level of effort for each author.

The statements also said little about how important a particular contribution was for project success.

Still, Dr Sauermann and his colleagues noted that author order has its own problems.

“When we talked to scientists, many think that there are certain norms, and they know how to interpret author order,” Dr Sauermann said. “But when you really push, it’s not clear at all, at least not at the level of detail we need.”

That’s further complicated by the fact that conventions of author order vary depending on the research field.

This work also revealed a difference of opinion between junior and senior researchers, with the former caring more strongly about contribution statements and how they are discussed and crafted.

“When we read open-ended responses to our survey questions, we got the impression of a really divided community,” Dr Sauermann said. “Some believe that forcing more detail in contribution statements is great, and some are concerned that it could really hurt teamwork and collaboration. It’s not that everyone is lukewarm; many really care.”

That level of interest could pave the way for more discussion, which is something Dr Sauermann said is ultimately needed for the scientific and research community to move forward and add more clarity to the process.

“This is not going to get any easier,” Dr Sauermann said. “It’s going to get harder as how we perform research changes and as teams get bigger and more diverse.”

Photo from Georgia Tech

Although many scientific journals try to provide details about authors’ contributions to a publication by requiring explicit statements, contribution statements get much less attention than authorship order, according to research published in Science Advances.

Researchers surveyed more than 6000 corresponding authors of studies published in recent years and found they consider contribution statements helpful for understanding the specific skills individual authors bring to a study.

However, the respondents said they still use author order for deciphering which authors did how much of the work and deserve most of the credit.

“The lack of uniformity and detail in contribution statements leaves open the door for varied interpretations, which could be why only a minority of respondents found them more useful than author order,” said Henry Sauermann, PhD, of ESMT Berlin in Germany.

Dr Sauermann and his colleagues also examined the relationship between author order and contribution statements on more than 12,000 published articles.

The contribution statements studied did include information about the types of work contributed by each author. However, multiple authors could be listed under the same contributions, and the statements had little information about the level of effort for each author.

The statements also said little about how important a particular contribution was for project success.

Still, Dr Sauermann and his colleagues noted that author order has its own problems.

“When we talked to scientists, many think that there are certain norms, and they know how to interpret author order,” Dr Sauermann said. “But when you really push, it’s not clear at all, at least not at the level of detail we need.”

That’s further complicated by the fact that conventions of author order vary depending on the research field.

This work also revealed a difference of opinion between junior and senior researchers, with the former caring more strongly about contribution statements and how they are discussed and crafted.

“When we read open-ended responses to our survey questions, we got the impression of a really divided community,” Dr Sauermann said. “Some believe that forcing more detail in contribution statements is great, and some are concerned that it could really hurt teamwork and collaboration. It’s not that everyone is lukewarm; many really care.”

That level of interest could pave the way for more discussion, which is something Dr Sauermann said is ultimately needed for the scientific and research community to move forward and add more clarity to the process.

“This is not going to get any easier,” Dr Sauermann said. “It’s going to get harder as how we perform research changes and as teams get bigger and more diverse.”

Photo from Georgia Tech

Although many scientific journals try to provide details about authors’ contributions to a publication by requiring explicit statements, contribution statements get much less attention than authorship order, according to research published in Science Advances.

Researchers surveyed more than 6000 corresponding authors of studies published in recent years and found they consider contribution statements helpful for understanding the specific skills individual authors bring to a study.

However, the respondents said they still use author order for deciphering which authors did how much of the work and deserve most of the credit.

“The lack of uniformity and detail in contribution statements leaves open the door for varied interpretations, which could be why only a minority of respondents found them more useful than author order,” said Henry Sauermann, PhD, of ESMT Berlin in Germany.

Dr Sauermann and his colleagues also examined the relationship between author order and contribution statements on more than 12,000 published articles.

The contribution statements studied did include information about the types of work contributed by each author. However, multiple authors could be listed under the same contributions, and the statements had little information about the level of effort for each author.

The statements also said little about how important a particular contribution was for project success.

Still, Dr Sauermann and his colleagues noted that author order has its own problems.

“When we talked to scientists, many think that there are certain norms, and they know how to interpret author order,” Dr Sauermann said. “But when you really push, it’s not clear at all, at least not at the level of detail we need.”

That’s further complicated by the fact that conventions of author order vary depending on the research field.

This work also revealed a difference of opinion between junior and senior researchers, with the former caring more strongly about contribution statements and how they are discussed and crafted.

“When we read open-ended responses to our survey questions, we got the impression of a really divided community,” Dr Sauermann said. “Some believe that forcing more detail in contribution statements is great, and some are concerned that it could really hurt teamwork and collaboration. It’s not that everyone is lukewarm; many really care.”

That level of interest could pave the way for more discussion, which is something Dr Sauermann said is ultimately needed for the scientific and research community to move forward and add more clarity to the process.

“This is not going to get any easier,” Dr Sauermann said. “It’s going to get harder as how we perform research changes and as teams get bigger and more diverse.”