SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

[email protected]

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

[email protected]

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

[email protected]

SAN FRANCISCO – Ketamine and the more recently Food and Drug Administration–approved esketamine have generated a great deal of excitement in psychiatry over their potential to treat depression and other psychiatric disorders. However, the mechanism of action is not completely understood, and efforts are underway to better understand the drugs.

Much has been made of ketamine’s interaction with the N-methyl-D-aspartate (NMDA) receptors. One belief is that chronic stress leads to the accumulation of extracellular glutamate, which leads to a range of negative consequences. Ketamine blocks excess glutamate in the synapse and may thus reverse these downstream effects.

But it may not be so clear cut, according to Nolan Williams, MD. During a session on ketamine’s mechanism of action at the annual meeting of the American Psychiatric Association, Dr. Williams, assistant professor of psychiatry and behavioral sciences at Stanford (Calif.) University, noted that ketamine is “one of the most dirty drugs we know. It affects most neurotransmitter systems and has all sorts of downstream effects.”

Pain research has already shown that ketamine’s mechanisms can be complex. It affects the opioid system, both directly and indirectly, and an opioid receptor antagonist blocks ketamine’s pain-relieving effect.

Since opioids are also known to have antidepressant effects, it’s natural to wonder if ketamine’s mechanism also involves the opioid system. The opioid antagonist naltrexone provides a tool to study the problem. Dr. Williams reasoned that if ketamine relies in whole or in part on the opioid system for its antidepressive effect, then administering naltrexone ahead of ketamine should blunt or even eliminate its efficacy.

To examine the question, the team conducted a study of 11 patients with treatment-resistant depression. Right away, it was clear that the participants had some bias toward the treatment. “They all said the same thing to me: ‘My psychiatrist said that your study doesn’t make any sense because this is an NMDA antagonist. I’m going to get two free ketamine infusions.’ So they were preloaded with this idea that they were going to get very potent antidepressant effects (even with naltrexone),” said Dr. Williams.

The study had a crossover design and included two ketamine infusions. Participants were randomized to get either naltrexone or placebo 1 hour before the first ketamine infusion, and then were allowed to relapse back to within 20% of their baseline depression score before receiving the second ketamine infusion, when they received naltrexone or placebo, whichever hadn’t been given in the first treatment.

Of 12 who completed the study, seven responded to placebo plus ketamine treatment, and six remitted. But when they crossed over to the naltrexone arm, the result was very different: In three of four measures, there was no significant difference between the pretreatment and posttreatment results. “The same people who were almost exclusively in remission during the ketamine plus placebo condition got nothing out of ketamine plus naltrexone,” said Dr. Williams. Naltrexone had a similar negating effect on the positive response to ketamine on the suicide item of the 17-item Hamilton Rating Scale for Depression.

The researchers also looked at whether ketamine’s dissociative effect could be responsible for its activity through altering the participant’s mental state, but determined that it may be necessary for the antidepressant effect – but it is not sufficient.

“What we concluded pretty strongly was that the opioid properties of ketamine are necessary to have the antidepressive effect. We’re not saying it’s sufficient, but it appears to be quite necessary,” Dr. Williams said. He added that the results don’t mean that ketamine’s effect on NMDA is unimportant. In fact, “it’s probable that the ketamine is driving the mood in a direction, and these glutamine-related changes are probably what’s maintaining the mood in that direction,” he added.

As to the clinical impacts of his findings, Dr. Williams emphasized the need to understand the mechanisms behind the ketamine class. He pointed out that in pivotal trials of esketamine, there were six deaths, three by suicide, all of them in the esketamine group. Surprisingly, two of those who took their own lives had scored a 0 on the Columbia-Suicide Severity Scale, both at baseline and at the visit immediately preceding their deaths. The score wasn’t available for the third. “These weren’t people who were particularly dangerously suicidal. So understanding the mechanism is really important to understanding the safety of this drug, who we should give it to, and what sorts of things we should watch out for,” Dr. Williams said.

The study was funded by the National Institutes of Health, Spectrum, the Brain and Behavior Research Foundation, and Stanford Bio-X. Dr. Williams had no disclosures.
 

SAN FRANCISCO – Ketamine and the more recently Food and Drug Administration–approved esketamine have generated a great deal of excitement in psychiatry over their potential to treat depression and other psychiatric disorders. However, the mechanism of action is not completely understood, and efforts are underway to better understand the drugs.

Much has been made of ketamine’s interaction with the N-methyl-D-aspartate (NMDA) receptors. One belief is that chronic stress leads to the accumulation of extracellular glutamate, which leads to a range of negative consequences. Ketamine blocks excess glutamate in the synapse and may thus reverse these downstream effects.

But it may not be so clear cut, according to Nolan Williams, MD. During a session on ketamine’s mechanism of action at the annual meeting of the American Psychiatric Association, Dr. Williams, assistant professor of psychiatry and behavioral sciences at Stanford (Calif.) University, noted that ketamine is “one of the most dirty drugs we know. It affects most neurotransmitter systems and has all sorts of downstream effects.”

Pain research has already shown that ketamine’s mechanisms can be complex. It affects the opioid system, both directly and indirectly, and an opioid receptor antagonist blocks ketamine’s pain-relieving effect.

Since opioids are also known to have antidepressant effects, it’s natural to wonder if ketamine’s mechanism also involves the opioid system. The opioid antagonist naltrexone provides a tool to study the problem. Dr. Williams reasoned that if ketamine relies in whole or in part on the opioid system for its antidepressive effect, then administering naltrexone ahead of ketamine should blunt or even eliminate its efficacy.

To examine the question, the team conducted a study of 11 patients with treatment-resistant depression. Right away, it was clear that the participants had some bias toward the treatment. “They all said the same thing to me: ‘My psychiatrist said that your study doesn’t make any sense because this is an NMDA antagonist. I’m going to get two free ketamine infusions.’ So they were preloaded with this idea that they were going to get very potent antidepressant effects (even with naltrexone),” said Dr. Williams.

The study had a crossover design and included two ketamine infusions. Participants were randomized to get either naltrexone or placebo 1 hour before the first ketamine infusion, and then were allowed to relapse back to within 20% of their baseline depression score before receiving the second ketamine infusion, when they received naltrexone or placebo, whichever hadn’t been given in the first treatment.

Of 12 who completed the study, seven responded to placebo plus ketamine treatment, and six remitted. But when they crossed over to the naltrexone arm, the result was very different: In three of four measures, there was no significant difference between the pretreatment and posttreatment results. “The same people who were almost exclusively in remission during the ketamine plus placebo condition got nothing out of ketamine plus naltrexone,” said Dr. Williams. Naltrexone had a similar negating effect on the positive response to ketamine on the suicide item of the 17-item Hamilton Rating Scale for Depression.

The researchers also looked at whether ketamine’s dissociative effect could be responsible for its activity through altering the participant’s mental state, but determined that it may be necessary for the antidepressant effect – but it is not sufficient.

“What we concluded pretty strongly was that the opioid properties of ketamine are necessary to have the antidepressive effect. We’re not saying it’s sufficient, but it appears to be quite necessary,” Dr. Williams said. He added that the results don’t mean that ketamine’s effect on NMDA is unimportant. In fact, “it’s probable that the ketamine is driving the mood in a direction, and these glutamine-related changes are probably what’s maintaining the mood in that direction,” he added.

As to the clinical impacts of his findings, Dr. Williams emphasized the need to understand the mechanisms behind the ketamine class. He pointed out that in pivotal trials of esketamine, there were six deaths, three by suicide, all of them in the esketamine group. Surprisingly, two of those who took their own lives had scored a 0 on the Columbia-Suicide Severity Scale, both at baseline and at the visit immediately preceding their deaths. The score wasn’t available for the third. “These weren’t people who were particularly dangerously suicidal. So understanding the mechanism is really important to understanding the safety of this drug, who we should give it to, and what sorts of things we should watch out for,” Dr. Williams said.

The study was funded by the National Institutes of Health, Spectrum, the Brain and Behavior Research Foundation, and Stanford Bio-X. Dr. Williams had no disclosures.
 

SAN FRANCISCO – Ketamine and the more recently Food and Drug Administration–approved esketamine have generated a great deal of excitement in psychiatry over their potential to treat depression and other psychiatric disorders. However, the mechanism of action is not completely understood, and efforts are underway to better understand the drugs.

Much has been made of ketamine’s interaction with the N-methyl-D-aspartate (NMDA) receptors. One belief is that chronic stress leads to the accumulation of extracellular glutamate, which leads to a range of negative consequences. Ketamine blocks excess glutamate in the synapse and may thus reverse these downstream effects.

But it may not be so clear cut, according to Nolan Williams, MD. During a session on ketamine’s mechanism of action at the annual meeting of the American Psychiatric Association, Dr. Williams, assistant professor of psychiatry and behavioral sciences at Stanford (Calif.) University, noted that ketamine is “one of the most dirty drugs we know. It affects most neurotransmitter systems and has all sorts of downstream effects.”

Pain research has already shown that ketamine’s mechanisms can be complex. It affects the opioid system, both directly and indirectly, and an opioid receptor antagonist blocks ketamine’s pain-relieving effect.

Since opioids are also known to have antidepressant effects, it’s natural to wonder if ketamine’s mechanism also involves the opioid system. The opioid antagonist naltrexone provides a tool to study the problem. Dr. Williams reasoned that if ketamine relies in whole or in part on the opioid system for its antidepressive effect, then administering naltrexone ahead of ketamine should blunt or even eliminate its efficacy.

To examine the question, the team conducted a study of 11 patients with treatment-resistant depression. Right away, it was clear that the participants had some bias toward the treatment. “They all said the same thing to me: ‘My psychiatrist said that your study doesn’t make any sense because this is an NMDA antagonist. I’m going to get two free ketamine infusions.’ So they were preloaded with this idea that they were going to get very potent antidepressant effects (even with naltrexone),” said Dr. Williams.

The study had a crossover design and included two ketamine infusions. Participants were randomized to get either naltrexone or placebo 1 hour before the first ketamine infusion, and then were allowed to relapse back to within 20% of their baseline depression score before receiving the second ketamine infusion, when they received naltrexone or placebo, whichever hadn’t been given in the first treatment.

Of 12 who completed the study, seven responded to placebo plus ketamine treatment, and six remitted. But when they crossed over to the naltrexone arm, the result was very different: In three of four measures, there was no significant difference between the pretreatment and posttreatment results. “The same people who were almost exclusively in remission during the ketamine plus placebo condition got nothing out of ketamine plus naltrexone,” said Dr. Williams. Naltrexone had a similar negating effect on the positive response to ketamine on the suicide item of the 17-item Hamilton Rating Scale for Depression.

The researchers also looked at whether ketamine’s dissociative effect could be responsible for its activity through altering the participant’s mental state, but determined that it may be necessary for the antidepressant effect – but it is not sufficient.

“What we concluded pretty strongly was that the opioid properties of ketamine are necessary to have the antidepressive effect. We’re not saying it’s sufficient, but it appears to be quite necessary,” Dr. Williams said. He added that the results don’t mean that ketamine’s effect on NMDA is unimportant. In fact, “it’s probable that the ketamine is driving the mood in a direction, and these glutamine-related changes are probably what’s maintaining the mood in that direction,” he added.

As to the clinical impacts of his findings, Dr. Williams emphasized the need to understand the mechanisms behind the ketamine class. He pointed out that in pivotal trials of esketamine, there were six deaths, three by suicide, all of them in the esketamine group. Surprisingly, two of those who took their own lives had scored a 0 on the Columbia-Suicide Severity Scale, both at baseline and at the visit immediately preceding their deaths. The score wasn’t available for the third. “These weren’t people who were particularly dangerously suicidal. So understanding the mechanism is really important to understanding the safety of this drug, who we should give it to, and what sorts of things we should watch out for,” Dr. Williams said.

The study was funded by the National Institutes of Health, Spectrum, the Brain and Behavior Research Foundation, and Stanford Bio-X. Dr. Williams had no disclosures.
 

NASHVILLE, TENN. – A novel rapid urine test strongly correlates with preeclampsia, according to findings from a study of urine samples from a prospective cohort of women referred to a labor and delivery triage center to rule out the condition.

The study involved the evaluation of 349 frozen urine samples from the cohort, which included 89 preeclampsia cases (26%) as diagnosed by expert adjudication based on 2013 American College of Obstetricians and Gynecologists guidelines. Visual scoring by a blinded user at 3 minutes after application of urine to the test device for 329 available samples showed 84% test sensitivity, 77% test specificity, and 93% negative predictive value, compared with the adjudicated diagnoses, Wendy L. Davis reported during an e-poster session at ACOG’s annual clinical and scientific meeting.

Of the women in the study cohort, 52% were multiparous, 91% were overweight or obese, 38% were early preterm, 31% were late preterm, and 31% were at term. Cases were described by at least one referring physician as “particularly challenging and ambiguous,” said Ms. Davis, founder and CEO of GestVision in Groton, Conn., and colleagues.

The findings, which suggest that this rapid test holds promise as an aid in the diagnosis of preeclampsia, are important as preeclampsia-associated morbidity and mortality most often occur because of a delay or misdiagnosis, they explained, also noting that diagnostic criteria for preeclampsia are “inadequate even in best care situations.”

The test – an in vitro diagnostic device known as the GestAssured Test Kit – is being developed by GestVision based on data showing that aberrant protein misfolding and aggregation is a pathogenic feature of preeclampsia. That data initially led to development of the Congo Red Dot test as a laboratory batch test, followed by development and validation of a point-of-care version of the test to allow for better integration in clinical work flow.

The GestAssured Test Kit currently in development for commercial use is based on that technology, and the current data suggest that it has slightly higher sensitivity, slightly lower specificity, and slightly higher negative predictive value than the Congo Red Dot test.

“The GestAssured test was developed specifically for preeclampsia and has a high negative predictive value, suggesting that this device, in conjunction with ACOG task force guidelines for hypertension in pregnancy, can assist in ruling out disease in patients suspected of preeclampsia,” the investigators wrote.

“[It is] particularly useful in a triage setting where you have a complex collection of patients coming in,” Ms. Davis said during the poster presentation. “And it warrants ongoing U.S. multicenter clinical studies.”

This study was funded by GestVision and Saving Lives at Birth. Ms. Davis is an employee and shareholder of GestVision and is named as an inventor or coinventor on patents licensed for commercialization to the company.

NASHVILLE, TENN. – A novel rapid urine test strongly correlates with preeclampsia, according to findings from a study of urine samples from a prospective cohort of women referred to a labor and delivery triage center to rule out the condition.

The study involved the evaluation of 349 frozen urine samples from the cohort, which included 89 preeclampsia cases (26%) as diagnosed by expert adjudication based on 2013 American College of Obstetricians and Gynecologists guidelines. Visual scoring by a blinded user at 3 minutes after application of urine to the test device for 329 available samples showed 84% test sensitivity, 77% test specificity, and 93% negative predictive value, compared with the adjudicated diagnoses, Wendy L. Davis reported during an e-poster session at ACOG’s annual clinical and scientific meeting.

Of the women in the study cohort, 52% were multiparous, 91% were overweight or obese, 38% were early preterm, 31% were late preterm, and 31% were at term. Cases were described by at least one referring physician as “particularly challenging and ambiguous,” said Ms. Davis, founder and CEO of GestVision in Groton, Conn., and colleagues.

The findings, which suggest that this rapid test holds promise as an aid in the diagnosis of preeclampsia, are important as preeclampsia-associated morbidity and mortality most often occur because of a delay or misdiagnosis, they explained, also noting that diagnostic criteria for preeclampsia are “inadequate even in best care situations.”

The test – an in vitro diagnostic device known as the GestAssured Test Kit – is being developed by GestVision based on data showing that aberrant protein misfolding and aggregation is a pathogenic feature of preeclampsia. That data initially led to development of the Congo Red Dot test as a laboratory batch test, followed by development and validation of a point-of-care version of the test to allow for better integration in clinical work flow.

The GestAssured Test Kit currently in development for commercial use is based on that technology, and the current data suggest that it has slightly higher sensitivity, slightly lower specificity, and slightly higher negative predictive value than the Congo Red Dot test.

“The GestAssured test was developed specifically for preeclampsia and has a high negative predictive value, suggesting that this device, in conjunction with ACOG task force guidelines for hypertension in pregnancy, can assist in ruling out disease in patients suspected of preeclampsia,” the investigators wrote.

“[It is] particularly useful in a triage setting where you have a complex collection of patients coming in,” Ms. Davis said during the poster presentation. “And it warrants ongoing U.S. multicenter clinical studies.”

This study was funded by GestVision and Saving Lives at Birth. Ms. Davis is an employee and shareholder of GestVision and is named as an inventor or coinventor on patents licensed for commercialization to the company.

NASHVILLE, TENN. – A novel rapid urine test strongly correlates with preeclampsia, according to findings from a study of urine samples from a prospective cohort of women referred to a labor and delivery triage center to rule out the condition.

The study involved the evaluation of 349 frozen urine samples from the cohort, which included 89 preeclampsia cases (26%) as diagnosed by expert adjudication based on 2013 American College of Obstetricians and Gynecologists guidelines. Visual scoring by a blinded user at 3 minutes after application of urine to the test device for 329 available samples showed 84% test sensitivity, 77% test specificity, and 93% negative predictive value, compared with the adjudicated diagnoses, Wendy L. Davis reported during an e-poster session at ACOG’s annual clinical and scientific meeting.

Of the women in the study cohort, 52% were multiparous, 91% were overweight or obese, 38% were early preterm, 31% were late preterm, and 31% were at term. Cases were described by at least one referring physician as “particularly challenging and ambiguous,” said Ms. Davis, founder and CEO of GestVision in Groton, Conn., and colleagues.

The findings, which suggest that this rapid test holds promise as an aid in the diagnosis of preeclampsia, are important as preeclampsia-associated morbidity and mortality most often occur because of a delay or misdiagnosis, they explained, also noting that diagnostic criteria for preeclampsia are “inadequate even in best care situations.”

The test – an in vitro diagnostic device known as the GestAssured Test Kit – is being developed by GestVision based on data showing that aberrant protein misfolding and aggregation is a pathogenic feature of preeclampsia. That data initially led to development of the Congo Red Dot test as a laboratory batch test, followed by development and validation of a point-of-care version of the test to allow for better integration in clinical work flow.

The GestAssured Test Kit currently in development for commercial use is based on that technology, and the current data suggest that it has slightly higher sensitivity, slightly lower specificity, and slightly higher negative predictive value than the Congo Red Dot test.

“The GestAssured test was developed specifically for preeclampsia and has a high negative predictive value, suggesting that this device, in conjunction with ACOG task force guidelines for hypertension in pregnancy, can assist in ruling out disease in patients suspected of preeclampsia,” the investigators wrote.

“[It is] particularly useful in a triage setting where you have a complex collection of patients coming in,” Ms. Davis said during the poster presentation. “And it warrants ongoing U.S. multicenter clinical studies.”

This study was funded by GestVision and Saving Lives at Birth. Ms. Davis is an employee and shareholder of GestVision and is named as an inventor or coinventor on patents licensed for commercialization to the company.

Goodnight, sleep tight ...

File this under creepy-crawly things you never wanted to learn about but now you know. New research into cimicid fossils (a.k.a. bed bugs) shows that the blood-sucking parasites are as old as the dinosaurs.

smuay/Getty Images

Bed bugs have been on earth for 115 million years – approximately the same amount of time it takes to get rid of them from your home.

Bats have long been assumed to be the ancestral host of these horrific pests, but a bed bug fossil shows that they precede bats by nearly 30 million years. The idea of a bed bug “fossil” is a little suspicious to us over here at LOTME, though, because we are pretty positive bed bugs only multiply and never die.

The new research, published in Cell, confirmed that the bed bug species had a major split into the two most common forms millions of years before humans arrived. Also confirmed: Dinosaurs clearly slept in beds, and that’s where bed bugs came from.
 

Dog person? It’s in the genes

Are you a total dog lover? Would you totally risk a little infectious bug if you got to play with some pups? Turns out, your love for Fido might be predicted by your DNA.

Jasmina007/Getty Images

An in-depth examination of the Swedish Twin Registry and national dog registers in Sweden found that genetic factors greatly contribute to dog ownership in Sweden. The study could not identify which genes are involved in our choices to keep dogs or if they related to evolution-related factors.

This is good news for dog people, though, because it suggests that if you love dogs, so does your family, and therefore you will be surrounded by dogs forever. At least that is what we’re choosing to believe.

This study could not be repeated with cat owners, because everyone knows cats own their humans, and the cats of Sweden were not interested in participating.
 

Gastroenterologists answer the big questions

Why does coffee make you poop? All coffee drinkers know this to be the case, and many even plan their mornings around it. But the real reason for this little side effect has always been a bit of a mystery.

Now, a group of researchers from the University of Texas may have an answer.

In a study presented at the annual Digestive Disease Week, the researchers fed coffee to rats for 3 days, analyzing their feces for changes in composition and bacterial make-up. (The joys of being a scientist.) They found that this diet suppressed the bacterial content of the feces; in addition, bacterial growth within the poop was suppressed when exposed to a 1.5% coffee solution on a petri dish.

An analysis of the rats’ intestines – dream job material right there – showed increased muscular motility. All of these effects occurred regardless of caffeine content.

And here’s a bonus: This was more than research just for research’s sake! The researchers claim that, given future study into the subject, coffee could be used as a treatment for ileus, a condition encountered after surgery where the intestines stop working. Apparently, it’s not just your brain that needs to be woken up – even your digestive system could use a coffee now and again.
 

Big honor for a small pharmaceutical partner

This week, we ask an important medical question: What’s your favorite microbe? Think about that for a minute while we discuss New Jersey’s new bacterial BFF. 

[email protected]

Goodnight, sleep tight ...

File this under creepy-crawly things you never wanted to learn about but now you know. New research into cimicid fossils (a.k.a. bed bugs) shows that the blood-sucking parasites are as old as the dinosaurs.

smuay/Getty Images

Bed bugs have been on earth for 115 million years – approximately the same amount of time it takes to get rid of them from your home.

Bats have long been assumed to be the ancestral host of these horrific pests, but a bed bug fossil shows that they precede bats by nearly 30 million years. The idea of a bed bug “fossil” is a little suspicious to us over here at LOTME, though, because we are pretty positive bed bugs only multiply and never die.

The new research, published in Cell, confirmed that the bed bug species had a major split into the two most common forms millions of years before humans arrived. Also confirmed: Dinosaurs clearly slept in beds, and that’s where bed bugs came from.
 

Dog person? It’s in the genes

Are you a total dog lover? Would you totally risk a little infectious bug if you got to play with some pups? Turns out, your love for Fido might be predicted by your DNA.

Jasmina007/Getty Images

An in-depth examination of the Swedish Twin Registry and national dog registers in Sweden found that genetic factors greatly contribute to dog ownership in Sweden. The study could not identify which genes are involved in our choices to keep dogs or if they related to evolution-related factors.

This is good news for dog people, though, because it suggests that if you love dogs, so does your family, and therefore you will be surrounded by dogs forever. At least that is what we’re choosing to believe.

This study could not be repeated with cat owners, because everyone knows cats own their humans, and the cats of Sweden were not interested in participating.
 

Gastroenterologists answer the big questions

Why does coffee make you poop? All coffee drinkers know this to be the case, and many even plan their mornings around it. But the real reason for this little side effect has always been a bit of a mystery.

Now, a group of researchers from the University of Texas may have an answer.

In a study presented at the annual Digestive Disease Week, the researchers fed coffee to rats for 3 days, analyzing their feces for changes in composition and bacterial make-up. (The joys of being a scientist.) They found that this diet suppressed the bacterial content of the feces; in addition, bacterial growth within the poop was suppressed when exposed to a 1.5% coffee solution on a petri dish.

An analysis of the rats’ intestines – dream job material right there – showed increased muscular motility. All of these effects occurred regardless of caffeine content.

And here’s a bonus: This was more than research just for research’s sake! The researchers claim that, given future study into the subject, coffee could be used as a treatment for ileus, a condition encountered after surgery where the intestines stop working. Apparently, it’s not just your brain that needs to be woken up – even your digestive system could use a coffee now and again.
 

Big honor for a small pharmaceutical partner

This week, we ask an important medical question: What’s your favorite microbe? Think about that for a minute while we discuss New Jersey’s new bacterial BFF. 

[email protected]

Goodnight, sleep tight ...

File this under creepy-crawly things you never wanted to learn about but now you know. New research into cimicid fossils (a.k.a. bed bugs) shows that the blood-sucking parasites are as old as the dinosaurs.

smuay/Getty Images

Bed bugs have been on earth for 115 million years – approximately the same amount of time it takes to get rid of them from your home.

Bats have long been assumed to be the ancestral host of these horrific pests, but a bed bug fossil shows that they precede bats by nearly 30 million years. The idea of a bed bug “fossil” is a little suspicious to us over here at LOTME, though, because we are pretty positive bed bugs only multiply and never die.

The new research, published in Cell, confirmed that the bed bug species had a major split into the two most common forms millions of years before humans arrived. Also confirmed: Dinosaurs clearly slept in beds, and that’s where bed bugs came from.
 

Dog person? It’s in the genes

Are you a total dog lover? Would you totally risk a little infectious bug if you got to play with some pups? Turns out, your love for Fido might be predicted by your DNA.

Jasmina007/Getty Images

An in-depth examination of the Swedish Twin Registry and national dog registers in Sweden found that genetic factors greatly contribute to dog ownership in Sweden. The study could not identify which genes are involved in our choices to keep dogs or if they related to evolution-related factors.

This is good news for dog people, though, because it suggests that if you love dogs, so does your family, and therefore you will be surrounded by dogs forever. At least that is what we’re choosing to believe.

This study could not be repeated with cat owners, because everyone knows cats own their humans, and the cats of Sweden were not interested in participating.
 

Gastroenterologists answer the big questions

Why does coffee make you poop? All coffee drinkers know this to be the case, and many even plan their mornings around it. But the real reason for this little side effect has always been a bit of a mystery.

Now, a group of researchers from the University of Texas may have an answer.

In a study presented at the annual Digestive Disease Week, the researchers fed coffee to rats for 3 days, analyzing their feces for changes in composition and bacterial make-up. (The joys of being a scientist.) They found that this diet suppressed the bacterial content of the feces; in addition, bacterial growth within the poop was suppressed when exposed to a 1.5% coffee solution on a petri dish.

An analysis of the rats’ intestines – dream job material right there – showed increased muscular motility. All of these effects occurred regardless of caffeine content.

And here’s a bonus: This was more than research just for research’s sake! The researchers claim that, given future study into the subject, coffee could be used as a treatment for ileus, a condition encountered after surgery where the intestines stop working. Apparently, it’s not just your brain that needs to be woken up – even your digestive system could use a coffee now and again.
 

Big honor for a small pharmaceutical partner

This week, we ask an important medical question: What’s your favorite microbe? Think about that for a minute while we discuss New Jersey’s new bacterial BFF. 

[email protected]

SAN DIEGO – In a multicenter study involving four academic medical centers, the addition of weight loss drugs to intragastric balloons resulted in better weight loss 12 months after balloon placement.

In a video interview at the annual Digestive Disease Week, study investigator Reem Sharaiha, MD, explained that one of the drawbacks of intragastric balloons is that, although they produce weight loss for the 6 or 12 months that they are in place, patients tend to regain that weight after they are removed. The study, involving 111 patients, was designed to determine whether the addition of weight loss drugs could mitigate this effect and improve weight loss, said Dr. Sharaiha of Weill Cornell Medical Center, New York.

Adding drugs such as metformin or weight loss drugs tailored to patients’ particular weight issues (cravings, anxiety, or fast gastric emptying) at the 3- or 6-month mark while the intragastric balloon was in place helped patients continue losing weight after balloon removal. At 12 months, the percentage of total body weight lost was significantly greater in the intragastric balloon group with concurrent pharmacotherapy (21.4% vs. 13.1%).

[email protected]

SOURCE: Shah SL et al. DDW 2019, Abstract 1105.

SAN DIEGO – In a multicenter study involving four academic medical centers, the addition of weight loss drugs to intragastric balloons resulted in better weight loss 12 months after balloon placement.

In a video interview at the annual Digestive Disease Week, study investigator Reem Sharaiha, MD, explained that one of the drawbacks of intragastric balloons is that, although they produce weight loss for the 6 or 12 months that they are in place, patients tend to regain that weight after they are removed. The study, involving 111 patients, was designed to determine whether the addition of weight loss drugs could mitigate this effect and improve weight loss, said Dr. Sharaiha of Weill Cornell Medical Center, New York.

Adding drugs such as metformin or weight loss drugs tailored to patients’ particular weight issues (cravings, anxiety, or fast gastric emptying) at the 3- or 6-month mark while the intragastric balloon was in place helped patients continue losing weight after balloon removal. At 12 months, the percentage of total body weight lost was significantly greater in the intragastric balloon group with concurrent pharmacotherapy (21.4% vs. 13.1%).

[email protected]

SOURCE: Shah SL et al. DDW 2019, Abstract 1105.

SAN DIEGO – In a multicenter study involving four academic medical centers, the addition of weight loss drugs to intragastric balloons resulted in better weight loss 12 months after balloon placement.

In a video interview at the annual Digestive Disease Week, study investigator Reem Sharaiha, MD, explained that one of the drawbacks of intragastric balloons is that, although they produce weight loss for the 6 or 12 months that they are in place, patients tend to regain that weight after they are removed. The study, involving 111 patients, was designed to determine whether the addition of weight loss drugs could mitigate this effect and improve weight loss, said Dr. Sharaiha of Weill Cornell Medical Center, New York.

Adding drugs such as metformin or weight loss drugs tailored to patients’ particular weight issues (cravings, anxiety, or fast gastric emptying) at the 3- or 6-month mark while the intragastric balloon was in place helped patients continue losing weight after balloon removal. At 12 months, the percentage of total body weight lost was significantly greater in the intragastric balloon group with concurrent pharmacotherapy (21.4% vs. 13.1%).

[email protected]

SOURCE: Shah SL et al. DDW 2019, Abstract 1105.

For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.

“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.

Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.

Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm³ or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).

Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm³.

The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).

The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.

The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”

The investigators did not disclose funding sources. They reported having no conflicts of interest.

SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.

For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.

“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.

Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.

Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm³ or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).

Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm³.

The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).

The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.

The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”

The investigators did not disclose funding sources. They reported having no conflicts of interest.

SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.

For patients with cirrhosis, variceal bleeding, and severe coagulopathies, the use of thromboelastography (TEG) to guide transfusion decisions significantly reduced both transfusions and rates of late rebleeding, according to the results of a randomized, open-label trial.

“With the use of TEG, only 13.3% of patients received any blood product, as compared with all patients in the conventional transfusion group,” wrote Gyanranjan Rout, MD, and associates at the All India Institute of Medical Sciences, a tertiary care center in New Delhi. The rate of rebleeding at 6 weeks was more than two-thirds lower with TEG versus the comparator group. The findings were published in the Journal of Clinical Gastroenterology.

Mortality remains high in patients with hepatic cirrhosis and variceal bleeding. Rebleeding is a major concern for these patients, and guidelines disagree on how to correct their coagulopathies so that they can undergo endoscopic treatment of varices. TEG “provides a global assessment of various factors promoting coagulation [platelets and clotting factors] and anticoagulation [fibrinolysis] in a single test,” the researchers noted.

Hence, they randomly assigned 60 adults with hepatic cirrhosis, acute variceal bleeding based on the Baveno VI consensus criteria, and significant coagulopathy (less than 50,000 platelets per mm³ or international normalized ratio under 1.8) to either conventional or TEG-guided transfusion. TEG of fresh blood was performed within 6 hours of hospital admission by using a MonoTEM-A automated thromboelastometer (Framar Hemologix, Rome).

Patients in the TEG group whose blood samples took more than 15 minutes to start forming fibrin received fresh frozen plasma (5 mL/kg of ideal body weight based on the Devine formula). Those whose maximum amplitude (an indicator of clot strength) was less than 30 mm received three units of platelets. Conventionally transfused patients received the same dose of fresh frozen plasma if their international normalized ratio was under 1.8 and the same amount of platelets if their platelet count was under 50,000 per mm³.

The groups had comparable baseline endoscopic findings, international normalized ratios, and hemoglobin and platelet levels. In the TEG group, only four (13.3%) patients underwent blood product transfusions, compared with every patient in the comparator group (P less than .001). Initial endoscopy showed similar control of bleeding between groups. At 5 days, rebleeding was noted in one (3.3%) TEG patient and four (13.3%) conventional transfusion patients (P = .167). At 42 days, this difference reached statistical significance (10% vs. 36.7%; P = .012).

The 6-week mortality rates were 13.3% in the TEG group and 26.7% in the conventional transfusion group (P = .176). The lack of statistical significance “can be explained by the fact that our study was not adequately powered to address the difference in mortality between the two study arms,” the researchers wrote.

The study excluded patients with sepsis, a major reason for coagulopathy in patients with cirrhosis. It also did not assess fibrinogen levels, and no patient received cryoprecipitate. “Our study provides initial data [supporting] the concept that TEG may help to decrease unnecessary blood transfusion and may even decrease 6-week rebleeding rate,” the researchers concluded. “However, this needs to be validated in a larger cohort of patients.”

The investigators did not disclose funding sources. They reported having no conflicts of interest.

SOURCE: Rout G et al. J Clin Gastroenterol. 2019 Apr 17. doi: 10.1097/MCG.000000000000121.

Grouping the term “transgender” in the abbreviation LGBT (lesbian, gay, bisexual, transgender) has historically been empowering for trans and gender nonconforming (GNC) persons. However, it also has contributed to the misunderstanding that gender identity is interchangeable with sexual identity. This common misconception can be a barrier to trans and GNC patients seeking care from ob.gyns. for their reproductive health needs.

Rawpixel/Thinkstock

By definition, gender identity refers to an internal experience of one’s gender, of one’s self.¹ While gender identity has social implications, it ultimately is something that a person experiences independently of interactions with others. By contrast, sexual orientation has an explicitly relational underpinning because sexual orientation involves attraction to others. The distinction between gender identity and sexual orientation is similar to an internal-versus-external, or a self-versus-other dichotomy. A further nuance to add is that sexual behavior does not always reflect sexual orientation, and sexual behavior can vary along a wide spectrum when gender identity is added to the equation.

Overall, health care providers should be careful not make assumptions about a patient’s sexual orientation based on a patient’s gender identity. When approaching a sexual history with any patient, but especially a transgender or GNC patient, providers should think deeply about what information is medically relevant.² The purpose of a sexual history is to identify behaviors that contribute to health risk, including pregnancy, sexually transmitted infection, and social problems such as sex-trafficking or intimate partner violence. The health care provider’s job is to ask questions that will uncover these risk factors.

With the advent of a more inclusive attitude toward gay and lesbian partnership, many providers already have learned to collect the sexual history without assuming the gender of a person’s sexual contacts. Still, when a provider is taking the sexual history, gender often is inappropriately used as proxy for the type of sex that a patient may be having. For example, a provider asking a cisgender woman about her sexual activity may ask, “how many sexual partners have you had in the last year?” But then, the provider may follow-up her response of “three sexual partners in the last year” by asking “men, women, or both?” By asking a patient if the patient’s sexual partners are “men, women, or both,” providers fail to accurately elucidate the risk factors that they are actually seeking when taking a sexual history. The cisgender woman from the above scenario may reply that she has been sleeping only with women for the last year, but if the sexual partners are transgender women, aka a woman who was assigned male at birth and therefore still may use her penis/testes for sexual purposes, then the patient actually may be at risk for pregnancy and may also have a different risk factor profile for sexually transmitted infections than if the patient were sexually active with cisgender women.

A different approach to using gender in taking the sexual history is to speak plainly about which sex organs come into contact during sexual activity. When patients identify as transgender or GNC, a provider first should start by asking them what language they would like providers to use when discussing sex organs.³ One example is that many trans men, both those who have undergone mastectomy as well as those who have not, may not use the word “breasts” to describe their “chests.” This distinction may make the difference between gaining and losing the trust of a trans/GNC patient in your clinic. After identifying how a patient would like to refer to sex organs, a provider can continue by asking which of the patient’s sex partners’ organs come into contact with the patient’s organs during sexual activity. Alternatively, starting with an even more broad line of questioning may be best for some patients, such as “how do you like to have sex?”

Carefully identifying the type of sex and what sex organs are involved has concrete medical implications. Patients assigned female at birth who are on hormone therapy with testosterone may need supportive care if they continue to use their vaginas in sexual encounters because testosterone can lead to a relatively hypoestrogenic state. Patients assigned male at birth who have undergone vaginoplasty procedures may need counseling about how to use and support their neovaginas as well as adjusted testing for dysplasia. Patients assigned female at birth who want to avoid pregnancy may need a nuanced consultation regarding contraception. These are just a few examples of how obstetrician-gynecologists can better support the sexual health of their trans/GNC patients by having an accurate understanding of how a trans/GNC person has sex.
 

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Bahng and Dr. Joyner reported no relevant financial disclosures

References

1. Sexual orientation and gender identity definitions. Human Rights Campaign.

2. Taking a sexual history from transgender people. Transforming Health at the Centers for Disease Control and Prevention.

3. Sexual health history: Talking sex with gender non-conforming and trans patients. National LGBT Health Education Center at The Fenway Institute.

Grouping the term “transgender” in the abbreviation LGBT (lesbian, gay, bisexual, transgender) has historically been empowering for trans and gender nonconforming (GNC) persons. However, it also has contributed to the misunderstanding that gender identity is interchangeable with sexual identity. This common misconception can be a barrier to trans and GNC patients seeking care from ob.gyns. for their reproductive health needs.

Rawpixel/Thinkstock

By definition, gender identity refers to an internal experience of one’s gender, of one’s self.¹ While gender identity has social implications, it ultimately is something that a person experiences independently of interactions with others. By contrast, sexual orientation has an explicitly relational underpinning because sexual orientation involves attraction to others. The distinction between gender identity and sexual orientation is similar to an internal-versus-external, or a self-versus-other dichotomy. A further nuance to add is that sexual behavior does not always reflect sexual orientation, and sexual behavior can vary along a wide spectrum when gender identity is added to the equation.

Overall, health care providers should be careful not make assumptions about a patient’s sexual orientation based on a patient’s gender identity. When approaching a sexual history with any patient, but especially a transgender or GNC patient, providers should think deeply about what information is medically relevant.² The purpose of a sexual history is to identify behaviors that contribute to health risk, including pregnancy, sexually transmitted infection, and social problems such as sex-trafficking or intimate partner violence. The health care provider’s job is to ask questions that will uncover these risk factors.

With the advent of a more inclusive attitude toward gay and lesbian partnership, many providers already have learned to collect the sexual history without assuming the gender of a person’s sexual contacts. Still, when a provider is taking the sexual history, gender often is inappropriately used as proxy for the type of sex that a patient may be having. For example, a provider asking a cisgender woman about her sexual activity may ask, “how many sexual partners have you had in the last year?” But then, the provider may follow-up her response of “three sexual partners in the last year” by asking “men, women, or both?” By asking a patient if the patient’s sexual partners are “men, women, or both,” providers fail to accurately elucidate the risk factors that they are actually seeking when taking a sexual history. The cisgender woman from the above scenario may reply that she has been sleeping only with women for the last year, but if the sexual partners are transgender women, aka a woman who was assigned male at birth and therefore still may use her penis/testes for sexual purposes, then the patient actually may be at risk for pregnancy and may also have a different risk factor profile for sexually transmitted infections than if the patient were sexually active with cisgender women.

A different approach to using gender in taking the sexual history is to speak plainly about which sex organs come into contact during sexual activity. When patients identify as transgender or GNC, a provider first should start by asking them what language they would like providers to use when discussing sex organs.³ One example is that many trans men, both those who have undergone mastectomy as well as those who have not, may not use the word “breasts” to describe their “chests.” This distinction may make the difference between gaining and losing the trust of a trans/GNC patient in your clinic. After identifying how a patient would like to refer to sex organs, a provider can continue by asking which of the patient’s sex partners’ organs come into contact with the patient’s organs during sexual activity. Alternatively, starting with an even more broad line of questioning may be best for some patients, such as “how do you like to have sex?”

Carefully identifying the type of sex and what sex organs are involved has concrete medical implications. Patients assigned female at birth who are on hormone therapy with testosterone may need supportive care if they continue to use their vaginas in sexual encounters because testosterone can lead to a relatively hypoestrogenic state. Patients assigned male at birth who have undergone vaginoplasty procedures may need counseling about how to use and support their neovaginas as well as adjusted testing for dysplasia. Patients assigned female at birth who want to avoid pregnancy may need a nuanced consultation regarding contraception. These are just a few examples of how obstetrician-gynecologists can better support the sexual health of their trans/GNC patients by having an accurate understanding of how a trans/GNC person has sex.
 

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Bahng and Dr. Joyner reported no relevant financial disclosures

References

1. Sexual orientation and gender identity definitions. Human Rights Campaign.

2. Taking a sexual history from transgender people. Transforming Health at the Centers for Disease Control and Prevention.

3. Sexual health history: Talking sex with gender non-conforming and trans patients. National LGBT Health Education Center at The Fenway Institute.

Grouping the term “transgender” in the abbreviation LGBT (lesbian, gay, bisexual, transgender) has historically been empowering for trans and gender nonconforming (GNC) persons. However, it also has contributed to the misunderstanding that gender identity is interchangeable with sexual identity. This common misconception can be a barrier to trans and GNC patients seeking care from ob.gyns. for their reproductive health needs.

Rawpixel/Thinkstock

By definition, gender identity refers to an internal experience of one’s gender, of one’s self.¹ While gender identity has social implications, it ultimately is something that a person experiences independently of interactions with others. By contrast, sexual orientation has an explicitly relational underpinning because sexual orientation involves attraction to others. The distinction between gender identity and sexual orientation is similar to an internal-versus-external, or a self-versus-other dichotomy. A further nuance to add is that sexual behavior does not always reflect sexual orientation, and sexual behavior can vary along a wide spectrum when gender identity is added to the equation.

Overall, health care providers should be careful not make assumptions about a patient’s sexual orientation based on a patient’s gender identity. When approaching a sexual history with any patient, but especially a transgender or GNC patient, providers should think deeply about what information is medically relevant.² The purpose of a sexual history is to identify behaviors that contribute to health risk, including pregnancy, sexually transmitted infection, and social problems such as sex-trafficking or intimate partner violence. The health care provider’s job is to ask questions that will uncover these risk factors.

With the advent of a more inclusive attitude toward gay and lesbian partnership, many providers already have learned to collect the sexual history without assuming the gender of a person’s sexual contacts. Still, when a provider is taking the sexual history, gender often is inappropriately used as proxy for the type of sex that a patient may be having. For example, a provider asking a cisgender woman about her sexual activity may ask, “how many sexual partners have you had in the last year?” But then, the provider may follow-up her response of “three sexual partners in the last year” by asking “men, women, or both?” By asking a patient if the patient’s sexual partners are “men, women, or both,” providers fail to accurately elucidate the risk factors that they are actually seeking when taking a sexual history. The cisgender woman from the above scenario may reply that she has been sleeping only with women for the last year, but if the sexual partners are transgender women, aka a woman who was assigned male at birth and therefore still may use her penis/testes for sexual purposes, then the patient actually may be at risk for pregnancy and may also have a different risk factor profile for sexually transmitted infections than if the patient were sexually active with cisgender women.

A different approach to using gender in taking the sexual history is to speak plainly about which sex organs come into contact during sexual activity. When patients identify as transgender or GNC, a provider first should start by asking them what language they would like providers to use when discussing sex organs.³ One example is that many trans men, both those who have undergone mastectomy as well as those who have not, may not use the word “breasts” to describe their “chests.” This distinction may make the difference between gaining and losing the trust of a trans/GNC patient in your clinic. After identifying how a patient would like to refer to sex organs, a provider can continue by asking which of the patient’s sex partners’ organs come into contact with the patient’s organs during sexual activity. Alternatively, starting with an even more broad line of questioning may be best for some patients, such as “how do you like to have sex?”

Carefully identifying the type of sex and what sex organs are involved has concrete medical implications. Patients assigned female at birth who are on hormone therapy with testosterone may need supportive care if they continue to use their vaginas in sexual encounters because testosterone can lead to a relatively hypoestrogenic state. Patients assigned male at birth who have undergone vaginoplasty procedures may need counseling about how to use and support their neovaginas as well as adjusted testing for dysplasia. Patients assigned female at birth who want to avoid pregnancy may need a nuanced consultation regarding contraception. These are just a few examples of how obstetrician-gynecologists can better support the sexual health of their trans/GNC patients by having an accurate understanding of how a trans/GNC person has sex.
 

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Bahng and Dr. Joyner reported no relevant financial disclosures

References

1. Sexual orientation and gender identity definitions. Human Rights Campaign.

2. Taking a sexual history from transgender people. Transforming Health at the Centers for Disease Control and Prevention.

3. Sexual health history: Talking sex with gender non-conforming and trans patients. National LGBT Health Education Center at The Fenway Institute.

MADISON, WISC. – Low-dose CT may one day represent an accessible, affordable, and safe imaging option to aid in diagnosis and management of spondyloarthritis, but it’s not quite ready for everyday use, said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”

An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”

Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”

Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.

“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.

A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.

In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).

The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.

Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).

The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.

Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.

“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.

Dr. Lambert reported no relevant conflicts of interest.

[email protected]

MADISON, WISC. – Low-dose CT may one day represent an accessible, affordable, and safe imaging option to aid in diagnosis and management of spondyloarthritis, but it’s not quite ready for everyday use, said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”

An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”

Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”

Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.

“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.

A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.

In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).

The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.

Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).

The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.

Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.

“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.

Dr. Lambert reported no relevant conflicts of interest.

[email protected]

MADISON, WISC. – Low-dose CT may one day represent an accessible, affordable, and safe imaging option to aid in diagnosis and management of spondyloarthritis, but it’s not quite ready for everyday use, said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”

An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”

Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”

Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.

“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.

A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.

In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).

The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.

Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).

The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.

Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.

“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.

Dr. Lambert reported no relevant conflicts of interest.

[email protected]

I’m sometimes asked what was different about practicing pediatrics when I was at the apex of my clinical career. Colored by the recent memory of several painful adjustments to unworkable and time-gobbling electronic medical record systems, I usually answer, “It was more fun before the damn computer landed in my exam room.” However, an op-ed piece in the New York Times has prompted me to reconsider how the practice of medicine has changed over the last 50 years (“An Era Defined by Fear,” by David Brooks, April 29, 2019).

Drazen Zigic/Getty Images

Mr. Brooks claims that the era in which we are living is defined by fear. He argues that beginning with the terrorist attacks of 9/11, fear has crept into every corner or our lives, influencing how we relate to one another and govern ourselves. Fueled by a media that feeds us “breaking news” at every hour of the day, we have become a country of people who see everything through the “dark filter” of fear.

I can recall monthly air raid drills during which my third-grade classmates and I scurried under our desks for what seemed hours. And I know my parents were concerned as polio swept through my hometown and the surrounding communities. But I don’t recall feeling the same omnipresent fear that I began to see over the last decade and a half of my practice.

Bombs never landed in Pleasantville, New York, and we knew our school was safe. Third graders today have been told that other third graders have been shot and killed in schools they thought were safe. I knew that there was a risk I might get my “bell rung” playing football. But neither my parents nor I worried that repeated concussions might hasten dementia. My parents and I knew that the weather was unpredictable, but we weren’t bombarded with warnings that the ocean might engulf our home or that the planet was dying.

I suspect my parents worried how I would find my way in the world, but not with the level of anxiety that I feel in parents today who are obsessed with their own fear of failure. And as David Brooks observes, “fear generates fear.” A fearful parent is likely to raise a fearful child. It’s not surprising that today’s pediatricians feel that their appointment lists are filled to the bursting point with patients who have mental health complaints, with anxiety and depression high on the list of diagnoses.

While fear is driving who and what we see in our offices, it also is coloring how we practice. Foremost among our fears is the threat of malpractice litigation. We are coached in risk management strategies, and although we may not admit it, many of us are practicing defensive medicine, a scourge that appeared only infrequently in my first 2 decades of practice. While rumors always could tarnish a physician’s reputation in a small town, the damage done by Internet trolls wielding the power of social media can be several orders of magnitude more devastating.

Not surprisingly, physicians like to practice in comfortable surroundings, which of course draw other physicians, and in short order physicians can find themselves facing the fear of competition. Before insurance companies controlled the landscape, physicians didn’t have to worry about maintaining a stable panel of patients. Now a physician must worry that he or she may be delisted on the whim of a committee of number crunchers. Although I always was concerned on keeping current, my accreditation was grandfathered, and I didn’t have to worry about maintenance of certification (MOC) exams and deadlines. And of course I completed my education with what I considered at the time a whopping $3,200 of debt, but at an interest rate so low that we could make more money in CDs (certificates of deposit).

I wish I could end with something of more substance than Franklin Roosevelt’s advice that the only thing to fear is fear itself. But I’m afraid I can’t.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

I’m sometimes asked what was different about practicing pediatrics when I was at the apex of my clinical career. Colored by the recent memory of several painful adjustments to unworkable and time-gobbling electronic medical record systems, I usually answer, “It was more fun before the damn computer landed in my exam room.” However, an op-ed piece in the New York Times has prompted me to reconsider how the practice of medicine has changed over the last 50 years (“An Era Defined by Fear,” by David Brooks, April 29, 2019).

Drazen Zigic/Getty Images

Mr. Brooks claims that the era in which we are living is defined by fear. He argues that beginning with the terrorist attacks of 9/11, fear has crept into every corner or our lives, influencing how we relate to one another and govern ourselves. Fueled by a media that feeds us “breaking news” at every hour of the day, we have become a country of people who see everything through the “dark filter” of fear.

I can recall monthly air raid drills during which my third-grade classmates and I scurried under our desks for what seemed hours. And I know my parents were concerned as polio swept through my hometown and the surrounding communities. But I don’t recall feeling the same omnipresent fear that I began to see over the last decade and a half of my practice.

Bombs never landed in Pleasantville, New York, and we knew our school was safe. Third graders today have been told that other third graders have been shot and killed in schools they thought were safe. I knew that there was a risk I might get my “bell rung” playing football. But neither my parents nor I worried that repeated concussions might hasten dementia. My parents and I knew that the weather was unpredictable, but we weren’t bombarded with warnings that the ocean might engulf our home or that the planet was dying.

I suspect my parents worried how I would find my way in the world, but not with the level of anxiety that I feel in parents today who are obsessed with their own fear of failure. And as David Brooks observes, “fear generates fear.” A fearful parent is likely to raise a fearful child. It’s not surprising that today’s pediatricians feel that their appointment lists are filled to the bursting point with patients who have mental health complaints, with anxiety and depression high on the list of diagnoses.

While fear is driving who and what we see in our offices, it also is coloring how we practice. Foremost among our fears is the threat of malpractice litigation. We are coached in risk management strategies, and although we may not admit it, many of us are practicing defensive medicine, a scourge that appeared only infrequently in my first 2 decades of practice. While rumors always could tarnish a physician’s reputation in a small town, the damage done by Internet trolls wielding the power of social media can be several orders of magnitude more devastating.

Not surprisingly, physicians like to practice in comfortable surroundings, which of course draw other physicians, and in short order physicians can find themselves facing the fear of competition. Before insurance companies controlled the landscape, physicians didn’t have to worry about maintaining a stable panel of patients. Now a physician must worry that he or she may be delisted on the whim of a committee of number crunchers. Although I always was concerned on keeping current, my accreditation was grandfathered, and I didn’t have to worry about maintenance of certification (MOC) exams and deadlines. And of course I completed my education with what I considered at the time a whopping $3,200 of debt, but at an interest rate so low that we could make more money in CDs (certificates of deposit).

I wish I could end with something of more substance than Franklin Roosevelt’s advice that the only thing to fear is fear itself. But I’m afraid I can’t.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

I’m sometimes asked what was different about practicing pediatrics when I was at the apex of my clinical career. Colored by the recent memory of several painful adjustments to unworkable and time-gobbling electronic medical record systems, I usually answer, “It was more fun before the damn computer landed in my exam room.” However, an op-ed piece in the New York Times has prompted me to reconsider how the practice of medicine has changed over the last 50 years (“An Era Defined by Fear,” by David Brooks, April 29, 2019).

Drazen Zigic/Getty Images

Mr. Brooks claims that the era in which we are living is defined by fear. He argues that beginning with the terrorist attacks of 9/11, fear has crept into every corner or our lives, influencing how we relate to one another and govern ourselves. Fueled by a media that feeds us “breaking news” at every hour of the day, we have become a country of people who see everything through the “dark filter” of fear.

I can recall monthly air raid drills during which my third-grade classmates and I scurried under our desks for what seemed hours. And I know my parents were concerned as polio swept through my hometown and the surrounding communities. But I don’t recall feeling the same omnipresent fear that I began to see over the last decade and a half of my practice.

Bombs never landed in Pleasantville, New York, and we knew our school was safe. Third graders today have been told that other third graders have been shot and killed in schools they thought were safe. I knew that there was a risk I might get my “bell rung” playing football. But neither my parents nor I worried that repeated concussions might hasten dementia. My parents and I knew that the weather was unpredictable, but we weren’t bombarded with warnings that the ocean might engulf our home or that the planet was dying.

I suspect my parents worried how I would find my way in the world, but not with the level of anxiety that I feel in parents today who are obsessed with their own fear of failure. And as David Brooks observes, “fear generates fear.” A fearful parent is likely to raise a fearful child. It’s not surprising that today’s pediatricians feel that their appointment lists are filled to the bursting point with patients who have mental health complaints, with anxiety and depression high on the list of diagnoses.

While fear is driving who and what we see in our offices, it also is coloring how we practice. Foremost among our fears is the threat of malpractice litigation. We are coached in risk management strategies, and although we may not admit it, many of us are practicing defensive medicine, a scourge that appeared only infrequently in my first 2 decades of practice. While rumors always could tarnish a physician’s reputation in a small town, the damage done by Internet trolls wielding the power of social media can be several orders of magnitude more devastating.

Not surprisingly, physicians like to practice in comfortable surroundings, which of course draw other physicians, and in short order physicians can find themselves facing the fear of competition. Before insurance companies controlled the landscape, physicians didn’t have to worry about maintaining a stable panel of patients. Now a physician must worry that he or she may be delisted on the whim of a committee of number crunchers. Although I always was concerned on keeping current, my accreditation was grandfathered, and I didn’t have to worry about maintenance of certification (MOC) exams and deadlines. And of course I completed my education with what I considered at the time a whopping $3,200 of debt, but at an interest rate so low that we could make more money in CDs (certificates of deposit).

I wish I could end with something of more substance than Franklin Roosevelt’s advice that the only thing to fear is fear itself. But I’m afraid I can’t.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].