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Transcranial magnetic stimulation shows promise in autism spectrum disorder
SAN FRANCISCO – , Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
“It’s a promising tool. There’s a lot of hope. There have been a range of scattered studies. But there is still a lot more work that needs to be done in terms of defining the optimal target structures in the brain, the dose and frequency of treatment, and which symptoms respond best,” said Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
The authors characterized transcranial magnetic stimulation (TMS) for autism spectrum disorder (ASD) as “a novel, possibly transformative approach” but added a strong cautionary note.
“The available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS [repetitive TMS] use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB [institutional review board]-approved research trial is premature pending further, adequately powered and controlled trials,” according to the white paper by the TMS in ASD Consensus Group (Autism Res. 2016 Feb;9[2]:184-203).
ASD support groups are eager to see TMS developed as a treatment, Dr. Hollander said. This is largely a result of the 2016 publication of a nonfiction book entitled, “Switched On: A Memoir of Brain Change and Emotional Awakening” (New York: Spiegel & Grau, 2016). Author John Elder Robison is a high-functioning individual with ASD who describes his dramatic improvement in response to TMS therapy in an early clinical trial conducted at Boston’s Beth Israel Deaconess Medical Center.
Dr. Hollander has been extensively involved in pioneering studies of TMS for the treatment of depression – currently its only Food and Drug Administration–approved indication – as well as for obsessive-compulsive disorder. His recent work on TMS for the treatment of ASD has focused on the noninvasive therapy’s ability to favorably affect the excitatory/inhibitory imbalance that characterizes ASD. This imbalance is tied chiefly to abnormal glutamatergic and gamma-aminobutyric acid–ergic neurotransmission in the neocortex, cerebellum, hippocampus, and amygdala. The imbalance is thought to be responsible for the cognitive, sensory, learning, memory, and motor deficits, as well as increased propensity for seizures, associated with ASD.
This excitatory/inhibitory imbalance is marked by increased cortical excitability and decreased inhibition within the densely packed cortical minicolumns of neurons, which are organized into pathways and circuits.
“You can use TMS as a treatment, or you can use it as a research probe to look at these mechanisms by turning on or off pathways,” the psychiatrist explained. “These densely packed minicolumns are like wires with poor insulation, which results in impairment in the ability to distinguish a stimulus from background noise. In the pathologic condition, you’re getting a rapid firing which doesn’t really differentiate what’s a true signal from what’s background noise.”
Therapeutically, TMS can be employed to improve that signal-to-noise ratio, either by reducing excitation or increasing inhibition. Potential TMS targets in autism include the anterior cingulate cortex, the supplementary or presupplementary motor area, the dorsal medial prefrontal cortex, the dorsal lateral prefrontal cortex, and the cerebellum. More than a dozen published TMS studies – albeit open-label, uncontrolled, and featuring only handfuls of patients – have demonstrated long-lasting improvements in the two core symptom domains of ASD: reduced repetitive behaviors and improved social relatedness and interpersonal functioning, Dr. Hollander said.
A wide range of associated noncore symptoms, including disruptive behaviors such as self-injury or aggression, impulse control, social anxiety, and depression, also might be targeted.
“In our clinical practice, we tend to treat adults with ASD who have a lot of OCD [obsessive-compulsive disorder] and repetitive behavior symptoms but also mood or anxiety symptoms or PTSD [posttraumatic stress disorder] symptoms as a result of earlier bullying. You can adapt your treatment to the target symptoms, so if there’s a lot of OCD-type symptoms, you might use low-frequency TMS at 1 Hz to target the supplementary motor area. If people are coming in with depressive symptoms, you can use the dorsolateral prefrontal cortex depression target. If they have a lot of anxiety, you can target the right frontal anxiety loop with low-frequency TMS. Or with a lot of PTSD symptoms, you can use high-frequency stimulation of the dorsolateral prefrontal cortex at 20 Hz,” Dr. Hollander said.
An important caveat, however, is that ASD is associated with an increased risk of seizures and other EEG abnormalities, so low-frequency TMS generally is preferable because of its greater safety.
Another challenge is administering TMS in children.
“Kids move around a lot, so you’re probably going to be using briefer stimulation parameters like theta burst stimulation rather than longer treatment parameters,” Dr. Hollander said.
That being said, there are more than two dozen published studies of TMS for treatment of children and adolescents, and surveys indicate that these patients generally find it quite tolerable. Dr. Hollander noted that in one study, children and adolescents ranked it somewhere between watching television and a long car ride. This placed TMS on the midrange of a tolerability scale: not as good as having a birthday party or playing a game, but better than going to the dentist, throwing up, or, in last place, getting a shot. Of the 39 youngsters, 34 indicated that they would recommend TMS to a friend.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to roughly half a dozen pharmaceutical companies.
SAN FRANCISCO – , Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
“It’s a promising tool. There’s a lot of hope. There have been a range of scattered studies. But there is still a lot more work that needs to be done in terms of defining the optimal target structures in the brain, the dose and frequency of treatment, and which symptoms respond best,” said Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
The authors characterized transcranial magnetic stimulation (TMS) for autism spectrum disorder (ASD) as “a novel, possibly transformative approach” but added a strong cautionary note.
“The available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS [repetitive TMS] use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB [institutional review board]-approved research trial is premature pending further, adequately powered and controlled trials,” according to the white paper by the TMS in ASD Consensus Group (Autism Res. 2016 Feb;9[2]:184-203).
ASD support groups are eager to see TMS developed as a treatment, Dr. Hollander said. This is largely a result of the 2016 publication of a nonfiction book entitled, “Switched On: A Memoir of Brain Change and Emotional Awakening” (New York: Spiegel & Grau, 2016). Author John Elder Robison is a high-functioning individual with ASD who describes his dramatic improvement in response to TMS therapy in an early clinical trial conducted at Boston’s Beth Israel Deaconess Medical Center.
Dr. Hollander has been extensively involved in pioneering studies of TMS for the treatment of depression – currently its only Food and Drug Administration–approved indication – as well as for obsessive-compulsive disorder. His recent work on TMS for the treatment of ASD has focused on the noninvasive therapy’s ability to favorably affect the excitatory/inhibitory imbalance that characterizes ASD. This imbalance is tied chiefly to abnormal glutamatergic and gamma-aminobutyric acid–ergic neurotransmission in the neocortex, cerebellum, hippocampus, and amygdala. The imbalance is thought to be responsible for the cognitive, sensory, learning, memory, and motor deficits, as well as increased propensity for seizures, associated with ASD.
This excitatory/inhibitory imbalance is marked by increased cortical excitability and decreased inhibition within the densely packed cortical minicolumns of neurons, which are organized into pathways and circuits.
“You can use TMS as a treatment, or you can use it as a research probe to look at these mechanisms by turning on or off pathways,” the psychiatrist explained. “These densely packed minicolumns are like wires with poor insulation, which results in impairment in the ability to distinguish a stimulus from background noise. In the pathologic condition, you’re getting a rapid firing which doesn’t really differentiate what’s a true signal from what’s background noise.”
Therapeutically, TMS can be employed to improve that signal-to-noise ratio, either by reducing excitation or increasing inhibition. Potential TMS targets in autism include the anterior cingulate cortex, the supplementary or presupplementary motor area, the dorsal medial prefrontal cortex, the dorsal lateral prefrontal cortex, and the cerebellum. More than a dozen published TMS studies – albeit open-label, uncontrolled, and featuring only handfuls of patients – have demonstrated long-lasting improvements in the two core symptom domains of ASD: reduced repetitive behaviors and improved social relatedness and interpersonal functioning, Dr. Hollander said.
A wide range of associated noncore symptoms, including disruptive behaviors such as self-injury or aggression, impulse control, social anxiety, and depression, also might be targeted.
“In our clinical practice, we tend to treat adults with ASD who have a lot of OCD [obsessive-compulsive disorder] and repetitive behavior symptoms but also mood or anxiety symptoms or PTSD [posttraumatic stress disorder] symptoms as a result of earlier bullying. You can adapt your treatment to the target symptoms, so if there’s a lot of OCD-type symptoms, you might use low-frequency TMS at 1 Hz to target the supplementary motor area. If people are coming in with depressive symptoms, you can use the dorsolateral prefrontal cortex depression target. If they have a lot of anxiety, you can target the right frontal anxiety loop with low-frequency TMS. Or with a lot of PTSD symptoms, you can use high-frequency stimulation of the dorsolateral prefrontal cortex at 20 Hz,” Dr. Hollander said.
An important caveat, however, is that ASD is associated with an increased risk of seizures and other EEG abnormalities, so low-frequency TMS generally is preferable because of its greater safety.
Another challenge is administering TMS in children.
“Kids move around a lot, so you’re probably going to be using briefer stimulation parameters like theta burst stimulation rather than longer treatment parameters,” Dr. Hollander said.
That being said, there are more than two dozen published studies of TMS for treatment of children and adolescents, and surveys indicate that these patients generally find it quite tolerable. Dr. Hollander noted that in one study, children and adolescents ranked it somewhere between watching television and a long car ride. This placed TMS on the midrange of a tolerability scale: not as good as having a birthday party or playing a game, but better than going to the dentist, throwing up, or, in last place, getting a shot. Of the 39 youngsters, 34 indicated that they would recommend TMS to a friend.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to roughly half a dozen pharmaceutical companies.
SAN FRANCISCO – , Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
“It’s a promising tool. There’s a lot of hope. There have been a range of scattered studies. But there is still a lot more work that needs to be done in terms of defining the optimal target structures in the brain, the dose and frequency of treatment, and which symptoms respond best,” said Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
The authors characterized transcranial magnetic stimulation (TMS) for autism spectrum disorder (ASD) as “a novel, possibly transformative approach” but added a strong cautionary note.
“The available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS [repetitive TMS] use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB [institutional review board]-approved research trial is premature pending further, adequately powered and controlled trials,” according to the white paper by the TMS in ASD Consensus Group (Autism Res. 2016 Feb;9[2]:184-203).
ASD support groups are eager to see TMS developed as a treatment, Dr. Hollander said. This is largely a result of the 2016 publication of a nonfiction book entitled, “Switched On: A Memoir of Brain Change and Emotional Awakening” (New York: Spiegel & Grau, 2016). Author John Elder Robison is a high-functioning individual with ASD who describes his dramatic improvement in response to TMS therapy in an early clinical trial conducted at Boston’s Beth Israel Deaconess Medical Center.
Dr. Hollander has been extensively involved in pioneering studies of TMS for the treatment of depression – currently its only Food and Drug Administration–approved indication – as well as for obsessive-compulsive disorder. His recent work on TMS for the treatment of ASD has focused on the noninvasive therapy’s ability to favorably affect the excitatory/inhibitory imbalance that characterizes ASD. This imbalance is tied chiefly to abnormal glutamatergic and gamma-aminobutyric acid–ergic neurotransmission in the neocortex, cerebellum, hippocampus, and amygdala. The imbalance is thought to be responsible for the cognitive, sensory, learning, memory, and motor deficits, as well as increased propensity for seizures, associated with ASD.
This excitatory/inhibitory imbalance is marked by increased cortical excitability and decreased inhibition within the densely packed cortical minicolumns of neurons, which are organized into pathways and circuits.
“You can use TMS as a treatment, or you can use it as a research probe to look at these mechanisms by turning on or off pathways,” the psychiatrist explained. “These densely packed minicolumns are like wires with poor insulation, which results in impairment in the ability to distinguish a stimulus from background noise. In the pathologic condition, you’re getting a rapid firing which doesn’t really differentiate what’s a true signal from what’s background noise.”
Therapeutically, TMS can be employed to improve that signal-to-noise ratio, either by reducing excitation or increasing inhibition. Potential TMS targets in autism include the anterior cingulate cortex, the supplementary or presupplementary motor area, the dorsal medial prefrontal cortex, the dorsal lateral prefrontal cortex, and the cerebellum. More than a dozen published TMS studies – albeit open-label, uncontrolled, and featuring only handfuls of patients – have demonstrated long-lasting improvements in the two core symptom domains of ASD: reduced repetitive behaviors and improved social relatedness and interpersonal functioning, Dr. Hollander said.
A wide range of associated noncore symptoms, including disruptive behaviors such as self-injury or aggression, impulse control, social anxiety, and depression, also might be targeted.
“In our clinical practice, we tend to treat adults with ASD who have a lot of OCD [obsessive-compulsive disorder] and repetitive behavior symptoms but also mood or anxiety symptoms or PTSD [posttraumatic stress disorder] symptoms as a result of earlier bullying. You can adapt your treatment to the target symptoms, so if there’s a lot of OCD-type symptoms, you might use low-frequency TMS at 1 Hz to target the supplementary motor area. If people are coming in with depressive symptoms, you can use the dorsolateral prefrontal cortex depression target. If they have a lot of anxiety, you can target the right frontal anxiety loop with low-frequency TMS. Or with a lot of PTSD symptoms, you can use high-frequency stimulation of the dorsolateral prefrontal cortex at 20 Hz,” Dr. Hollander said.
An important caveat, however, is that ASD is associated with an increased risk of seizures and other EEG abnormalities, so low-frequency TMS generally is preferable because of its greater safety.
Another challenge is administering TMS in children.
“Kids move around a lot, so you’re probably going to be using briefer stimulation parameters like theta burst stimulation rather than longer treatment parameters,” Dr. Hollander said.
That being said, there are more than two dozen published studies of TMS for treatment of children and adolescents, and surveys indicate that these patients generally find it quite tolerable. Dr. Hollander noted that in one study, children and adolescents ranked it somewhere between watching television and a long car ride. This placed TMS on the midrange of a tolerability scale: not as good as having a birthday party or playing a game, but better than going to the dentist, throwing up, or, in last place, getting a shot. Of the 39 youngsters, 34 indicated that they would recommend TMS to a friend.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to roughly half a dozen pharmaceutical companies.
EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
Enasidenib monotherapy responses in 37% with relapsed/refractory AML and IDH2 mutations
MADRID –
Among 214 patients treated at a dose level of 100 mg daily, the overall response rate was 37%, including 20.1% complete responses (CRs) and 7.9% complete responses with incomplete recovery of platelets (CRp) or incomplete hematologic recovery (CRi), reported Eytan M. Stein, MD, an internist and hematologic oncologist at the Memorial Sloan Kettering Cancer Center in New York.
“In patients with relapsed/refractory AML (with IDH2 mutations), most of whom had received multiple prior AML treatments, enasidenib induced durable CRs that were associated with overall survival of greater than 8 months,” he said at the annual congress of the European Hematology Association.
The IDH2 gene encodes for isocitrate dehydrogenase 2, which is an enzyme of the citric acid cycle. An estimated 8%-15% of patients with AML have mutations in IDH2 that cause intracellular accumulation of beta-hydroxyglutarate, which leads to blockage of myeloblast differentiation through a variety of mechanisms. The primary mechanism of action of enasidenib appears to be through its action on differentiation, rather than through cytotoxicity, Dr. Stein said.
He reported updated results from the fully enrolled cohorts of the phase 1/2 study. Earlier data from the study were reported at the 2017 annual meeting of the American Society of Clinical Oncology and in a paper published concurrently in Blood.
In the study, the investigators first enrolled 113 patients with advanced hematologic malignancies with IDH2 mutations and treated them with cumulative daily doses of enasidenib ranging from 50 to 650 mg.
In a phase 1 expansion study at the established dose of 100 mg daily, 126 patients with IDH2 mutations were enrolled in one of four cohorts: patients aged 60 or older with relapsed or refractory AML or AML patients of any age who experienced a relapse after undergoing a bone marrow transplant (BMT); patients under age 60 except those with post-BMT relapses; patients with previously untreated AML who were 60 years or older who declined the standard of care; and patients with other hematologic malignancies who were ineligible for other study arms.
The study also included a phase 2 expansion cohort of 106 patients with relapsed/refractory AML with IDH2 mutations treated with enasidenib 100 mg daily. The data cutoff was Oct. 14, 2016.
Among 214 patients treated at the 100-mg/day dose, the ORR was 37%, including 20.1% with a CR, 7.9% with a CRp or CRi, 3.7% with partial responses, and 5.1% with a morphologic leukemia-free state.
The median time to first response was 1.9 months, and the median time to CR was 3.7 months.
Clinicians should wait until patients have received at least four cycles of the drug before determining whether they should be continued on the drug or switched to another therapy, Dr. Stein said.
After 30 months of follow-up, overall survival (OS) among the 281 patients with relapsed/refractory AML with IDH2 mutations who were treated with enasidenib at any dose level was 8.4 months. Among the 214 treated at the 100-mg daily dose level, the median OS was 8.3 months.
When the investigators looked at OS by best response, they saw that patients who had a CR had a median OS of 22.9 months. For patients with responses other than CR, the median OS was 15.1 months. For patients with no response to the drug, the median OS was 5.6 months.
Patients generally tolerated the drug well. Most adverse events were grade 1 or 2 in severity.
An increase in blood bilirubin was the most frequent grade 3 or 4 adverse event, occurring in 8% of all patients. The effect was caused by an off-target reaction and was not associated with elevations in liver enzymes or evidence of liver damage, Dr. Stein said.
Grade 3 or 4 dyspnea occurred in 6% of patients, and 7% of all patients had serious treatment-related IDH-inhibitor–associated differentiation syndrome (IDH-DS). This syndrome presents with symptoms similar to those of retinoic acid syndrome, which occurs during treatment for acute promyelocytic leukemia.
Enasidenib is being explored in a phase 3 study comparing enasidenib monotherapy with conventional care in patients with late-stage AML and in combination with other agents and regimens in phase 1/2 studies in patients with newly diagnosed AML with IDH2 mutations.
Enasidenib has been granted priority review by the U.S. Food and Drug Administration for relapsed/refractory AML with an IDH2 mutation and has been given a Prescription Drug User Fee Act action date of Aug. 30, 2017, according to Celgene.
The study was funded by Celgene. Dr. Stein disclosed a consulting/advisory role with the company, research funding, and travel expenses.
MADRID –
Among 214 patients treated at a dose level of 100 mg daily, the overall response rate was 37%, including 20.1% complete responses (CRs) and 7.9% complete responses with incomplete recovery of platelets (CRp) or incomplete hematologic recovery (CRi), reported Eytan M. Stein, MD, an internist and hematologic oncologist at the Memorial Sloan Kettering Cancer Center in New York.
“In patients with relapsed/refractory AML (with IDH2 mutations), most of whom had received multiple prior AML treatments, enasidenib induced durable CRs that were associated with overall survival of greater than 8 months,” he said at the annual congress of the European Hematology Association.
The IDH2 gene encodes for isocitrate dehydrogenase 2, which is an enzyme of the citric acid cycle. An estimated 8%-15% of patients with AML have mutations in IDH2 that cause intracellular accumulation of beta-hydroxyglutarate, which leads to blockage of myeloblast differentiation through a variety of mechanisms. The primary mechanism of action of enasidenib appears to be through its action on differentiation, rather than through cytotoxicity, Dr. Stein said.
He reported updated results from the fully enrolled cohorts of the phase 1/2 study. Earlier data from the study were reported at the 2017 annual meeting of the American Society of Clinical Oncology and in a paper published concurrently in Blood.
In the study, the investigators first enrolled 113 patients with advanced hematologic malignancies with IDH2 mutations and treated them with cumulative daily doses of enasidenib ranging from 50 to 650 mg.
In a phase 1 expansion study at the established dose of 100 mg daily, 126 patients with IDH2 mutations were enrolled in one of four cohorts: patients aged 60 or older with relapsed or refractory AML or AML patients of any age who experienced a relapse after undergoing a bone marrow transplant (BMT); patients under age 60 except those with post-BMT relapses; patients with previously untreated AML who were 60 years or older who declined the standard of care; and patients with other hematologic malignancies who were ineligible for other study arms.
The study also included a phase 2 expansion cohort of 106 patients with relapsed/refractory AML with IDH2 mutations treated with enasidenib 100 mg daily. The data cutoff was Oct. 14, 2016.
Among 214 patients treated at the 100-mg/day dose, the ORR was 37%, including 20.1% with a CR, 7.9% with a CRp or CRi, 3.7% with partial responses, and 5.1% with a morphologic leukemia-free state.
The median time to first response was 1.9 months, and the median time to CR was 3.7 months.
Clinicians should wait until patients have received at least four cycles of the drug before determining whether they should be continued on the drug or switched to another therapy, Dr. Stein said.
After 30 months of follow-up, overall survival (OS) among the 281 patients with relapsed/refractory AML with IDH2 mutations who were treated with enasidenib at any dose level was 8.4 months. Among the 214 treated at the 100-mg daily dose level, the median OS was 8.3 months.
When the investigators looked at OS by best response, they saw that patients who had a CR had a median OS of 22.9 months. For patients with responses other than CR, the median OS was 15.1 months. For patients with no response to the drug, the median OS was 5.6 months.
Patients generally tolerated the drug well. Most adverse events were grade 1 or 2 in severity.
An increase in blood bilirubin was the most frequent grade 3 or 4 adverse event, occurring in 8% of all patients. The effect was caused by an off-target reaction and was not associated with elevations in liver enzymes or evidence of liver damage, Dr. Stein said.
Grade 3 or 4 dyspnea occurred in 6% of patients, and 7% of all patients had serious treatment-related IDH-inhibitor–associated differentiation syndrome (IDH-DS). This syndrome presents with symptoms similar to those of retinoic acid syndrome, which occurs during treatment for acute promyelocytic leukemia.
Enasidenib is being explored in a phase 3 study comparing enasidenib monotherapy with conventional care in patients with late-stage AML and in combination with other agents and regimens in phase 1/2 studies in patients with newly diagnosed AML with IDH2 mutations.
Enasidenib has been granted priority review by the U.S. Food and Drug Administration for relapsed/refractory AML with an IDH2 mutation and has been given a Prescription Drug User Fee Act action date of Aug. 30, 2017, according to Celgene.
The study was funded by Celgene. Dr. Stein disclosed a consulting/advisory role with the company, research funding, and travel expenses.
MADRID –
Among 214 patients treated at a dose level of 100 mg daily, the overall response rate was 37%, including 20.1% complete responses (CRs) and 7.9% complete responses with incomplete recovery of platelets (CRp) or incomplete hematologic recovery (CRi), reported Eytan M. Stein, MD, an internist and hematologic oncologist at the Memorial Sloan Kettering Cancer Center in New York.
“In patients with relapsed/refractory AML (with IDH2 mutations), most of whom had received multiple prior AML treatments, enasidenib induced durable CRs that were associated with overall survival of greater than 8 months,” he said at the annual congress of the European Hematology Association.
The IDH2 gene encodes for isocitrate dehydrogenase 2, which is an enzyme of the citric acid cycle. An estimated 8%-15% of patients with AML have mutations in IDH2 that cause intracellular accumulation of beta-hydroxyglutarate, which leads to blockage of myeloblast differentiation through a variety of mechanisms. The primary mechanism of action of enasidenib appears to be through its action on differentiation, rather than through cytotoxicity, Dr. Stein said.
He reported updated results from the fully enrolled cohorts of the phase 1/2 study. Earlier data from the study were reported at the 2017 annual meeting of the American Society of Clinical Oncology and in a paper published concurrently in Blood.
In the study, the investigators first enrolled 113 patients with advanced hematologic malignancies with IDH2 mutations and treated them with cumulative daily doses of enasidenib ranging from 50 to 650 mg.
In a phase 1 expansion study at the established dose of 100 mg daily, 126 patients with IDH2 mutations were enrolled in one of four cohorts: patients aged 60 or older with relapsed or refractory AML or AML patients of any age who experienced a relapse after undergoing a bone marrow transplant (BMT); patients under age 60 except those with post-BMT relapses; patients with previously untreated AML who were 60 years or older who declined the standard of care; and patients with other hematologic malignancies who were ineligible for other study arms.
The study also included a phase 2 expansion cohort of 106 patients with relapsed/refractory AML with IDH2 mutations treated with enasidenib 100 mg daily. The data cutoff was Oct. 14, 2016.
Among 214 patients treated at the 100-mg/day dose, the ORR was 37%, including 20.1% with a CR, 7.9% with a CRp or CRi, 3.7% with partial responses, and 5.1% with a morphologic leukemia-free state.
The median time to first response was 1.9 months, and the median time to CR was 3.7 months.
Clinicians should wait until patients have received at least four cycles of the drug before determining whether they should be continued on the drug or switched to another therapy, Dr. Stein said.
After 30 months of follow-up, overall survival (OS) among the 281 patients with relapsed/refractory AML with IDH2 mutations who were treated with enasidenib at any dose level was 8.4 months. Among the 214 treated at the 100-mg daily dose level, the median OS was 8.3 months.
When the investigators looked at OS by best response, they saw that patients who had a CR had a median OS of 22.9 months. For patients with responses other than CR, the median OS was 15.1 months. For patients with no response to the drug, the median OS was 5.6 months.
Patients generally tolerated the drug well. Most adverse events were grade 1 or 2 in severity.
An increase in blood bilirubin was the most frequent grade 3 or 4 adverse event, occurring in 8% of all patients. The effect was caused by an off-target reaction and was not associated with elevations in liver enzymes or evidence of liver damage, Dr. Stein said.
Grade 3 or 4 dyspnea occurred in 6% of patients, and 7% of all patients had serious treatment-related IDH-inhibitor–associated differentiation syndrome (IDH-DS). This syndrome presents with symptoms similar to those of retinoic acid syndrome, which occurs during treatment for acute promyelocytic leukemia.
Enasidenib is being explored in a phase 3 study comparing enasidenib monotherapy with conventional care in patients with late-stage AML and in combination with other agents and regimens in phase 1/2 studies in patients with newly diagnosed AML with IDH2 mutations.
Enasidenib has been granted priority review by the U.S. Food and Drug Administration for relapsed/refractory AML with an IDH2 mutation and has been given a Prescription Drug User Fee Act action date of Aug. 30, 2017, according to Celgene.
The study was funded by Celgene. Dr. Stein disclosed a consulting/advisory role with the company, research funding, and travel expenses.
AT EHA 2017
Key clinical point: Approximately 12% of patients with acute myeloid leukemia have mutations in IDH2, the target of the investigational agent enasidenib.
Major finding: Among 214 patients treated at a dose level of 100 mg daily, the overall response rate was 37%.
Data source: A phase 1/2 study in patients with relapsed/refractory AML and other hematologic malignancies with mutations in IDH2.
Disclosures: The study was funded by Celgene. Dr. Stein disclosed a consulting/advisory role with the company, research funding, and travel expenses.
Don’t forget about Zika
Although the Zika virus isn’t making as many news headlines as it was last summer, ob.gyns. must not forget that it could still be in our waiting rooms.
Last year, new information on Zika emerged on a weekly, sometimes daily, basis. Today, ob.gyns. remain on the front lines of counseling and treating women whose pregnancies are at risk of being affected by the Zika virus and devastating birth defects associated with it.
The American College of Obstetricians and Gynecologists prioritizes preparing ob.gyns. to comprehensively address the Zika virus with patients. To support clinicians, ACOG regularly develops, updates, and issues guidance on the risk, prevention, assessment, treatment, and outcomes of the Zika virus. This includes a regularly updated Practice Advisory, as well as information to direct ob.gyns. to critical resources from the Centers for Disease Control and Prevention, such as the U.S. Zika Pregnancy Registry.
Last month, I participated in an ad hoc meeting of international experts and professional society representatives sponsored by the Gottesfeld-Hohler Memorial Foundation. The goal of this Zika think tank was to share ongoing studies and unpublished findings and to identify ways for the groups to collaborate to fight the virus. Zika experts from endemic and risk areas, such as Brazil, Colombia, Puerto Rico, Texas, and Florida, started the meeting with on-the-ground updates. The latest epidemiologic evidence is that there appear to be waves of Zika virus infections that occur across regions/countries, spreading to virus-naive areas. Although immunity may develop eventually, Zika appears to occur in epidemics and is likely to spread further in North and South America to naive regions. Much of the United States is at risk during mosquito seasons. This collaboration with the Gottesfeld-Hohler Memorial Foundation was just the beginning, and I look forward to working more with Zika experts from all over the world.
The health reform debate in Washington also will affect our ability to respond to the ongoing Zika crisis. Current proposals allow states to opt out of essential coverage requirements, such as contraception and maternity coverage. It also would limit the federal investment in Medicaid, resulting in cuts to benefits and provider reimbursement and hamstringing our ability to treat our low-income pregnant patients with Zika exposure.
As ob.gyns., we continue to be the most important source of information for patients, and our goals of providing the most up-to-date knowledge and aiding in informed decision making are more important than ever.
Dr. Harris is a gynecologist in Gainesville, Fla., and chair of ACOG District VII. She reported having no relevant financial disclosures.
Although the Zika virus isn’t making as many news headlines as it was last summer, ob.gyns. must not forget that it could still be in our waiting rooms.
Last year, new information on Zika emerged on a weekly, sometimes daily, basis. Today, ob.gyns. remain on the front lines of counseling and treating women whose pregnancies are at risk of being affected by the Zika virus and devastating birth defects associated with it.
The American College of Obstetricians and Gynecologists prioritizes preparing ob.gyns. to comprehensively address the Zika virus with patients. To support clinicians, ACOG regularly develops, updates, and issues guidance on the risk, prevention, assessment, treatment, and outcomes of the Zika virus. This includes a regularly updated Practice Advisory, as well as information to direct ob.gyns. to critical resources from the Centers for Disease Control and Prevention, such as the U.S. Zika Pregnancy Registry.
Last month, I participated in an ad hoc meeting of international experts and professional society representatives sponsored by the Gottesfeld-Hohler Memorial Foundation. The goal of this Zika think tank was to share ongoing studies and unpublished findings and to identify ways for the groups to collaborate to fight the virus. Zika experts from endemic and risk areas, such as Brazil, Colombia, Puerto Rico, Texas, and Florida, started the meeting with on-the-ground updates. The latest epidemiologic evidence is that there appear to be waves of Zika virus infections that occur across regions/countries, spreading to virus-naive areas. Although immunity may develop eventually, Zika appears to occur in epidemics and is likely to spread further in North and South America to naive regions. Much of the United States is at risk during mosquito seasons. This collaboration with the Gottesfeld-Hohler Memorial Foundation was just the beginning, and I look forward to working more with Zika experts from all over the world.
The health reform debate in Washington also will affect our ability to respond to the ongoing Zika crisis. Current proposals allow states to opt out of essential coverage requirements, such as contraception and maternity coverage. It also would limit the federal investment in Medicaid, resulting in cuts to benefits and provider reimbursement and hamstringing our ability to treat our low-income pregnant patients with Zika exposure.
As ob.gyns., we continue to be the most important source of information for patients, and our goals of providing the most up-to-date knowledge and aiding in informed decision making are more important than ever.
Dr. Harris is a gynecologist in Gainesville, Fla., and chair of ACOG District VII. She reported having no relevant financial disclosures.
Although the Zika virus isn’t making as many news headlines as it was last summer, ob.gyns. must not forget that it could still be in our waiting rooms.
Last year, new information on Zika emerged on a weekly, sometimes daily, basis. Today, ob.gyns. remain on the front lines of counseling and treating women whose pregnancies are at risk of being affected by the Zika virus and devastating birth defects associated with it.
The American College of Obstetricians and Gynecologists prioritizes preparing ob.gyns. to comprehensively address the Zika virus with patients. To support clinicians, ACOG regularly develops, updates, and issues guidance on the risk, prevention, assessment, treatment, and outcomes of the Zika virus. This includes a regularly updated Practice Advisory, as well as information to direct ob.gyns. to critical resources from the Centers for Disease Control and Prevention, such as the U.S. Zika Pregnancy Registry.
Last month, I participated in an ad hoc meeting of international experts and professional society representatives sponsored by the Gottesfeld-Hohler Memorial Foundation. The goal of this Zika think tank was to share ongoing studies and unpublished findings and to identify ways for the groups to collaborate to fight the virus. Zika experts from endemic and risk areas, such as Brazil, Colombia, Puerto Rico, Texas, and Florida, started the meeting with on-the-ground updates. The latest epidemiologic evidence is that there appear to be waves of Zika virus infections that occur across regions/countries, spreading to virus-naive areas. Although immunity may develop eventually, Zika appears to occur in epidemics and is likely to spread further in North and South America to naive regions. Much of the United States is at risk during mosquito seasons. This collaboration with the Gottesfeld-Hohler Memorial Foundation was just the beginning, and I look forward to working more with Zika experts from all over the world.
The health reform debate in Washington also will affect our ability to respond to the ongoing Zika crisis. Current proposals allow states to opt out of essential coverage requirements, such as contraception and maternity coverage. It also would limit the federal investment in Medicaid, resulting in cuts to benefits and provider reimbursement and hamstringing our ability to treat our low-income pregnant patients with Zika exposure.
As ob.gyns., we continue to be the most important source of information for patients, and our goals of providing the most up-to-date knowledge and aiding in informed decision making are more important than ever.
Dr. Harris is a gynecologist in Gainesville, Fla., and chair of ACOG District VII. She reported having no relevant financial disclosures.
Listening for golf balls
“What did the patient say about the golf ball?” I asked my student.
The student looked blank. “Golf ball?” he asked.
“The patient said a golf ball hit him.”
“He did?”
“I showed him a precancerous red spot on his forehead, and said I could freeze it off.”
“Yes,” said the student. “Now I remember.”
“Good. Now tell me why he said it.”
The student looked lost. “Because he really was hit by a golf ball?”
“Maybe he was,” I said. “But in his 60 years, he’s been hit by a lot of things. How can he be sure the golf ball hit just that spot? And anyhow, why tell me about it? He must have thought it was important for me to know. We discussed this the other day,” I reminded him.
“Because there was trauma?”
“That’s it,” I said. “One way patients understand why things happen to them is by saying that what got sick was hit by something. They assume trauma weakens and damages the body, and disposes it to being unhealthy.
“After all,” I went on, “I had told him his spot was caused by sun exposure. But he’s had sun exposure all over his face, so why would he get a sun spot only right there? His answer: Sun damages all skin, but the part the golf ball whacked is especially susceptible.
“Is he right? I have no idea, but it’s important – to him – to think so. Not so much for this spot – we’re going to treat it anyway – but because of what he said 2 minutes later about his left shin. Remember?”
The student did not.
“He had a raised brown spot on his leg,” I reminded him. “It was just a seborrheic keratosis, not even precancerous. But he said he was always picking it.”
“Yes, he did say that,” said the student.
“So again: Why did he think I needed to know?”
“Because picking is a form of trauma, which might cause the spot to turn into something?”
“Yes, indeed,” I said. “You should train yourself to listen to these offhand remarks that seem irrelevant to you. They are relevant to the patient, or he wouldn’t say them.
Sure enough, a little later the student and I met another patient coming for a skin check. A computer scientist from a local university, he displayed a big collection of cherry angiomas on his torso, front, and back.
Looking at his belly, he said, “I know where I got those.”
“Which ones?” I asked.
He pointed to a dense collection of red spots near his navel. “A soccer ball hit me there when I was a teenager in Colombia,” he said.
Later, the student and I discussed this man’s recollection. “What makes his observation striking,” I suggested, “is not just as another example of a patient blaming body changes on trauma. It’s that he did it in a way that even a smidgen of critical thinking – the kind he applies to his professional work all the time – would show that his hypothesis makes no sense. After all, he has dozens of red spots nowhere near where the soccer ball supposedly hit him.
“You would think a computer scientist would notice this, but when it comes to looking at our own health, even sophisticated scientific training may not help. Instead, the thinking is: “I’ve got these red spots. Something caused them. A soccer ball hit me down there. That must be it.”
Sometimes hearing what patients say doesn’t matter; we’re not going to remove the cherry angiomas. But sometimes it does, by telling us the real reason they want something removed, which may include some guilt about their own picking, guilt they can do without.
But you would have to listen for that nuance, and listening is hard. Mostly, in medicine and in life, we hear only what we expect to hear.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected]
“What did the patient say about the golf ball?” I asked my student.
The student looked blank. “Golf ball?” he asked.
“The patient said a golf ball hit him.”
“He did?”
“I showed him a precancerous red spot on his forehead, and said I could freeze it off.”
“Yes,” said the student. “Now I remember.”
“Good. Now tell me why he said it.”
The student looked lost. “Because he really was hit by a golf ball?”
“Maybe he was,” I said. “But in his 60 years, he’s been hit by a lot of things. How can he be sure the golf ball hit just that spot? And anyhow, why tell me about it? He must have thought it was important for me to know. We discussed this the other day,” I reminded him.
“Because there was trauma?”
“That’s it,” I said. “One way patients understand why things happen to them is by saying that what got sick was hit by something. They assume trauma weakens and damages the body, and disposes it to being unhealthy.
“After all,” I went on, “I had told him his spot was caused by sun exposure. But he’s had sun exposure all over his face, so why would he get a sun spot only right there? His answer: Sun damages all skin, but the part the golf ball whacked is especially susceptible.
“Is he right? I have no idea, but it’s important – to him – to think so. Not so much for this spot – we’re going to treat it anyway – but because of what he said 2 minutes later about his left shin. Remember?”
The student did not.
“He had a raised brown spot on his leg,” I reminded him. “It was just a seborrheic keratosis, not even precancerous. But he said he was always picking it.”
“Yes, he did say that,” said the student.
“So again: Why did he think I needed to know?”
“Because picking is a form of trauma, which might cause the spot to turn into something?”
“Yes, indeed,” I said. “You should train yourself to listen to these offhand remarks that seem irrelevant to you. They are relevant to the patient, or he wouldn’t say them.
Sure enough, a little later the student and I met another patient coming for a skin check. A computer scientist from a local university, he displayed a big collection of cherry angiomas on his torso, front, and back.
Looking at his belly, he said, “I know where I got those.”
“Which ones?” I asked.
He pointed to a dense collection of red spots near his navel. “A soccer ball hit me there when I was a teenager in Colombia,” he said.
Later, the student and I discussed this man’s recollection. “What makes his observation striking,” I suggested, “is not just as another example of a patient blaming body changes on trauma. It’s that he did it in a way that even a smidgen of critical thinking – the kind he applies to his professional work all the time – would show that his hypothesis makes no sense. After all, he has dozens of red spots nowhere near where the soccer ball supposedly hit him.
“You would think a computer scientist would notice this, but when it comes to looking at our own health, even sophisticated scientific training may not help. Instead, the thinking is: “I’ve got these red spots. Something caused them. A soccer ball hit me down there. That must be it.”
Sometimes hearing what patients say doesn’t matter; we’re not going to remove the cherry angiomas. But sometimes it does, by telling us the real reason they want something removed, which may include some guilt about their own picking, guilt they can do without.
But you would have to listen for that nuance, and listening is hard. Mostly, in medicine and in life, we hear only what we expect to hear.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected]
“What did the patient say about the golf ball?” I asked my student.
The student looked blank. “Golf ball?” he asked.
“The patient said a golf ball hit him.”
“He did?”
“I showed him a precancerous red spot on his forehead, and said I could freeze it off.”
“Yes,” said the student. “Now I remember.”
“Good. Now tell me why he said it.”
The student looked lost. “Because he really was hit by a golf ball?”
“Maybe he was,” I said. “But in his 60 years, he’s been hit by a lot of things. How can he be sure the golf ball hit just that spot? And anyhow, why tell me about it? He must have thought it was important for me to know. We discussed this the other day,” I reminded him.
“Because there was trauma?”
“That’s it,” I said. “One way patients understand why things happen to them is by saying that what got sick was hit by something. They assume trauma weakens and damages the body, and disposes it to being unhealthy.
“After all,” I went on, “I had told him his spot was caused by sun exposure. But he’s had sun exposure all over his face, so why would he get a sun spot only right there? His answer: Sun damages all skin, but the part the golf ball whacked is especially susceptible.
“Is he right? I have no idea, but it’s important – to him – to think so. Not so much for this spot – we’re going to treat it anyway – but because of what he said 2 minutes later about his left shin. Remember?”
The student did not.
“He had a raised brown spot on his leg,” I reminded him. “It was just a seborrheic keratosis, not even precancerous. But he said he was always picking it.”
“Yes, he did say that,” said the student.
“So again: Why did he think I needed to know?”
“Because picking is a form of trauma, which might cause the spot to turn into something?”
“Yes, indeed,” I said. “You should train yourself to listen to these offhand remarks that seem irrelevant to you. They are relevant to the patient, or he wouldn’t say them.
Sure enough, a little later the student and I met another patient coming for a skin check. A computer scientist from a local university, he displayed a big collection of cherry angiomas on his torso, front, and back.
Looking at his belly, he said, “I know where I got those.”
“Which ones?” I asked.
He pointed to a dense collection of red spots near his navel. “A soccer ball hit me there when I was a teenager in Colombia,” he said.
Later, the student and I discussed this man’s recollection. “What makes his observation striking,” I suggested, “is not just as another example of a patient blaming body changes on trauma. It’s that he did it in a way that even a smidgen of critical thinking – the kind he applies to his professional work all the time – would show that his hypothesis makes no sense. After all, he has dozens of red spots nowhere near where the soccer ball supposedly hit him.
“You would think a computer scientist would notice this, but when it comes to looking at our own health, even sophisticated scientific training may not help. Instead, the thinking is: “I’ve got these red spots. Something caused them. A soccer ball hit me down there. That must be it.”
Sometimes hearing what patients say doesn’t matter; we’re not going to remove the cherry angiomas. But sometimes it does, by telling us the real reason they want something removed, which may include some guilt about their own picking, guilt they can do without.
But you would have to listen for that nuance, and listening is hard. Mostly, in medicine and in life, we hear only what we expect to hear.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected]
How primary care physicians can hit the mark on contraceptive counseling
SAN FRANCISCO – When it comes to counseling women about contraceptive care and family planning, many primary care physicians fall short, according to Christine Dehlendorf, MD.
“Providing contraceptive care and family planning care is part of what we do as preventive care for women of reproductive age, but we don’t always do it as often as we should,” Dr. Dehlendorf said at the UCSF Annual Advances in Internal Medicine meeting. “We don’t often take the initiative of making sure that women’s contraceptive needs are being met at all visits when we engage with them.”
“Many of you might think that’s okay, because we’re only talking about it when women come in for family planning visits,” said Dr. Dehlendorf of the departments of family and community medicine and obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. “In fact, this is something that is an ongoing need for women. We should be using every opportunity to make sure we’re helping them, even if it’s just by initiating the conversation and providing referrals as appropriate.”
Some might think that the best approach to contraceptive decision making involves recommending the most highly effective methods, such as long-acting reversible contraceptives, which have a risk of failure that’s 20 times lower than that of short-acting hormonal methods. Examples of counseling approaches used in that context include tiered effectiveness, in which the clinician presents methods in order of effectiveness, and motivational interviewing, a counseling approach developed for use in people with addictions.
However, Dr. Dehlendorf said she prefers to view contraceptive choice as a decision driven by women’s values and preferences.
“We know that effectiveness is very important to women, but we also know that things like side-effect profile and control over the [contraceptive] method are important as well,” she explained. “These strong features reflect women’s different assessments of the desirability of different outcomes associated with contraceptive use.
“For example, some women think that the possibility of amenorrhea with progestin IUDs or Depo-Provera is a great thing, and other people think it would be horrible,” Dr. Dehlendorf noted. “It has nothing to do with safety or effectiveness; this has to do with how women view that characteristic in the context of their own values and preferences.”
The differential value that women may place on contraceptive effectiveness also relates to different perceptions they have of the possibility of an unplanned pregnancy in their lives, and how important that is to avoid.
“In general, in the public health and clinical dialogue, the idea is that an unplanned pregnancy is an inherently bad pregnancy,” Dr. Dehlendorf said. “The conventional dialogue involves the notion of intentions and plans: Are they intending or planning to get pregnant? Intentions being timing-based ideas of when to get pregnant, and plans being concrete steps they take to act on those intentions.”
However, an emerging body of literature has shown that there are other dimensions of how women think about the possibility of pregnancy in their lives that are distinct from intentions and plans, she said, such as desire, which is how strongly they intend or don’t intend to have a pregnancy, and feelings, their emotional orientation around the potential for a pregnancy in their life.
“You could argue that this is overcomplicating things, but that is not true,” Dr. Dehlendorf said. “Plans, intentions, desires, and feelings are all different concepts, and some of them are more or less relevant to individual women, and they don’t always align with each other. That’s very much in conflict with how we conventionally talk about pregnancy in women’s lives.”
Examples from qualitative research have fleshed this out.
In one recently published study, researchers led by Jenny A. Higgins, PhD, of the department of gender and women’s studies at the University of Wisconsin–Madison, asked women about their views on IUDs. One woman said, “I guess one of the reasons that I haven’t gotten an IUD yet is like, I don’t know, having one kid already and being in a long-term committed relationship, it takes the element of surprise out of when we would have our next kid, which I kind of want. I’m in that weird position. I just don’t want to put too much thought and planning into when I have my next kid.”
Other women view an unplanned pregnancy as emotionally welcome.
In a longitudinal study that measured prospective pregnancy intentions and feelings among 403 women in Austin, Tex., one woman said, “Another pregnancy is definitely not the right path for me, and I’m being very careful with birth control. But if I somehow ended up pregnant, would I embrace it and think it’s for the best? Absolutely.”
Another study participant said, “I don’t want more kids and was hoping to get my tubes tied. We can’t afford another one. But if it happened, I’d still be happy. I’d be really excited. We’d rise to the occasion. Nothing would really change” (Soc Sci Med. 2015 May;132:149-155).
According to Dr. Dehlendorf, the lesson from such studies is that women are going to assess the importance of the efficacy of their contraceptive method differently, depending on how important it is for them to prevent an unintended pregnancy.
“They’re not going to make a decision about effectiveness the way we as clinicians might think that they should,” she said. “So, assuming that highly effective methods are the best methods for all women because of their effectiveness ignores the variability in preferences, and it also doesn’t take into account women’s strong feelings about other aspects of contraceptive use, such as bleeding profiles and control over their methods.”
Shared decision making may be the best way to help women make a choice based on their preferences. In a study that Dr. Dehlendorf and her associates conducted in 348 women who were seen for contraceptive care in the San Francisco Bay area, two habits were associated with contraceptive continuation: investing in the beginning, and eliciting the patient’s perspective (Am J Obstet Gynecol. 2016 Jul;215[1]:78.e1-9). “Investing in the beginning consists of greeting the patient warmly, making small talk, and treating the patient as a person,” she said. “That was the most highly influential aspect of the interaction. Building rapport and decision support helps women choose a method that’s a good fit for them.
“We also know that women like this method of counseling, but this approach might not be for everyone,” Dr. Dehlendorf cautioned. “Some women don’t want your suggestions, even if it’s grounded in their preferences. They just want to get the method that they came in for. The right thing is to acknowledge that, but you can also ask women if they want to hear about other methods, because some women might not know about all of their options.”
Dr. Dehlendorf reported having no relevant financial disclosures.
SAN FRANCISCO – When it comes to counseling women about contraceptive care and family planning, many primary care physicians fall short, according to Christine Dehlendorf, MD.
“Providing contraceptive care and family planning care is part of what we do as preventive care for women of reproductive age, but we don’t always do it as often as we should,” Dr. Dehlendorf said at the UCSF Annual Advances in Internal Medicine meeting. “We don’t often take the initiative of making sure that women’s contraceptive needs are being met at all visits when we engage with them.”
“Many of you might think that’s okay, because we’re only talking about it when women come in for family planning visits,” said Dr. Dehlendorf of the departments of family and community medicine and obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. “In fact, this is something that is an ongoing need for women. We should be using every opportunity to make sure we’re helping them, even if it’s just by initiating the conversation and providing referrals as appropriate.”
Some might think that the best approach to contraceptive decision making involves recommending the most highly effective methods, such as long-acting reversible contraceptives, which have a risk of failure that’s 20 times lower than that of short-acting hormonal methods. Examples of counseling approaches used in that context include tiered effectiveness, in which the clinician presents methods in order of effectiveness, and motivational interviewing, a counseling approach developed for use in people with addictions.
However, Dr. Dehlendorf said she prefers to view contraceptive choice as a decision driven by women’s values and preferences.
“We know that effectiveness is very important to women, but we also know that things like side-effect profile and control over the [contraceptive] method are important as well,” she explained. “These strong features reflect women’s different assessments of the desirability of different outcomes associated with contraceptive use.
“For example, some women think that the possibility of amenorrhea with progestin IUDs or Depo-Provera is a great thing, and other people think it would be horrible,” Dr. Dehlendorf noted. “It has nothing to do with safety or effectiveness; this has to do with how women view that characteristic in the context of their own values and preferences.”
The differential value that women may place on contraceptive effectiveness also relates to different perceptions they have of the possibility of an unplanned pregnancy in their lives, and how important that is to avoid.
“In general, in the public health and clinical dialogue, the idea is that an unplanned pregnancy is an inherently bad pregnancy,” Dr. Dehlendorf said. “The conventional dialogue involves the notion of intentions and plans: Are they intending or planning to get pregnant? Intentions being timing-based ideas of when to get pregnant, and plans being concrete steps they take to act on those intentions.”
However, an emerging body of literature has shown that there are other dimensions of how women think about the possibility of pregnancy in their lives that are distinct from intentions and plans, she said, such as desire, which is how strongly they intend or don’t intend to have a pregnancy, and feelings, their emotional orientation around the potential for a pregnancy in their life.
“You could argue that this is overcomplicating things, but that is not true,” Dr. Dehlendorf said. “Plans, intentions, desires, and feelings are all different concepts, and some of them are more or less relevant to individual women, and they don’t always align with each other. That’s very much in conflict with how we conventionally talk about pregnancy in women’s lives.”
Examples from qualitative research have fleshed this out.
In one recently published study, researchers led by Jenny A. Higgins, PhD, of the department of gender and women’s studies at the University of Wisconsin–Madison, asked women about their views on IUDs. One woman said, “I guess one of the reasons that I haven’t gotten an IUD yet is like, I don’t know, having one kid already and being in a long-term committed relationship, it takes the element of surprise out of when we would have our next kid, which I kind of want. I’m in that weird position. I just don’t want to put too much thought and planning into when I have my next kid.”
Other women view an unplanned pregnancy as emotionally welcome.
In a longitudinal study that measured prospective pregnancy intentions and feelings among 403 women in Austin, Tex., one woman said, “Another pregnancy is definitely not the right path for me, and I’m being very careful with birth control. But if I somehow ended up pregnant, would I embrace it and think it’s for the best? Absolutely.”
Another study participant said, “I don’t want more kids and was hoping to get my tubes tied. We can’t afford another one. But if it happened, I’d still be happy. I’d be really excited. We’d rise to the occasion. Nothing would really change” (Soc Sci Med. 2015 May;132:149-155).
According to Dr. Dehlendorf, the lesson from such studies is that women are going to assess the importance of the efficacy of their contraceptive method differently, depending on how important it is for them to prevent an unintended pregnancy.
“They’re not going to make a decision about effectiveness the way we as clinicians might think that they should,” she said. “So, assuming that highly effective methods are the best methods for all women because of their effectiveness ignores the variability in preferences, and it also doesn’t take into account women’s strong feelings about other aspects of contraceptive use, such as bleeding profiles and control over their methods.”
Shared decision making may be the best way to help women make a choice based on their preferences. In a study that Dr. Dehlendorf and her associates conducted in 348 women who were seen for contraceptive care in the San Francisco Bay area, two habits were associated with contraceptive continuation: investing in the beginning, and eliciting the patient’s perspective (Am J Obstet Gynecol. 2016 Jul;215[1]:78.e1-9). “Investing in the beginning consists of greeting the patient warmly, making small talk, and treating the patient as a person,” she said. “That was the most highly influential aspect of the interaction. Building rapport and decision support helps women choose a method that’s a good fit for them.
“We also know that women like this method of counseling, but this approach might not be for everyone,” Dr. Dehlendorf cautioned. “Some women don’t want your suggestions, even if it’s grounded in their preferences. They just want to get the method that they came in for. The right thing is to acknowledge that, but you can also ask women if they want to hear about other methods, because some women might not know about all of their options.”
Dr. Dehlendorf reported having no relevant financial disclosures.
SAN FRANCISCO – When it comes to counseling women about contraceptive care and family planning, many primary care physicians fall short, according to Christine Dehlendorf, MD.
“Providing contraceptive care and family planning care is part of what we do as preventive care for women of reproductive age, but we don’t always do it as often as we should,” Dr. Dehlendorf said at the UCSF Annual Advances in Internal Medicine meeting. “We don’t often take the initiative of making sure that women’s contraceptive needs are being met at all visits when we engage with them.”
“Many of you might think that’s okay, because we’re only talking about it when women come in for family planning visits,” said Dr. Dehlendorf of the departments of family and community medicine and obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. “In fact, this is something that is an ongoing need for women. We should be using every opportunity to make sure we’re helping them, even if it’s just by initiating the conversation and providing referrals as appropriate.”
Some might think that the best approach to contraceptive decision making involves recommending the most highly effective methods, such as long-acting reversible contraceptives, which have a risk of failure that’s 20 times lower than that of short-acting hormonal methods. Examples of counseling approaches used in that context include tiered effectiveness, in which the clinician presents methods in order of effectiveness, and motivational interviewing, a counseling approach developed for use in people with addictions.
However, Dr. Dehlendorf said she prefers to view contraceptive choice as a decision driven by women’s values and preferences.
“We know that effectiveness is very important to women, but we also know that things like side-effect profile and control over the [contraceptive] method are important as well,” she explained. “These strong features reflect women’s different assessments of the desirability of different outcomes associated with contraceptive use.
“For example, some women think that the possibility of amenorrhea with progestin IUDs or Depo-Provera is a great thing, and other people think it would be horrible,” Dr. Dehlendorf noted. “It has nothing to do with safety or effectiveness; this has to do with how women view that characteristic in the context of their own values and preferences.”
The differential value that women may place on contraceptive effectiveness also relates to different perceptions they have of the possibility of an unplanned pregnancy in their lives, and how important that is to avoid.
“In general, in the public health and clinical dialogue, the idea is that an unplanned pregnancy is an inherently bad pregnancy,” Dr. Dehlendorf said. “The conventional dialogue involves the notion of intentions and plans: Are they intending or planning to get pregnant? Intentions being timing-based ideas of when to get pregnant, and plans being concrete steps they take to act on those intentions.”
However, an emerging body of literature has shown that there are other dimensions of how women think about the possibility of pregnancy in their lives that are distinct from intentions and plans, she said, such as desire, which is how strongly they intend or don’t intend to have a pregnancy, and feelings, their emotional orientation around the potential for a pregnancy in their life.
“You could argue that this is overcomplicating things, but that is not true,” Dr. Dehlendorf said. “Plans, intentions, desires, and feelings are all different concepts, and some of them are more or less relevant to individual women, and they don’t always align with each other. That’s very much in conflict with how we conventionally talk about pregnancy in women’s lives.”
Examples from qualitative research have fleshed this out.
In one recently published study, researchers led by Jenny A. Higgins, PhD, of the department of gender and women’s studies at the University of Wisconsin–Madison, asked women about their views on IUDs. One woman said, “I guess one of the reasons that I haven’t gotten an IUD yet is like, I don’t know, having one kid already and being in a long-term committed relationship, it takes the element of surprise out of when we would have our next kid, which I kind of want. I’m in that weird position. I just don’t want to put too much thought and planning into when I have my next kid.”
Other women view an unplanned pregnancy as emotionally welcome.
In a longitudinal study that measured prospective pregnancy intentions and feelings among 403 women in Austin, Tex., one woman said, “Another pregnancy is definitely not the right path for me, and I’m being very careful with birth control. But if I somehow ended up pregnant, would I embrace it and think it’s for the best? Absolutely.”
Another study participant said, “I don’t want more kids and was hoping to get my tubes tied. We can’t afford another one. But if it happened, I’d still be happy. I’d be really excited. We’d rise to the occasion. Nothing would really change” (Soc Sci Med. 2015 May;132:149-155).
According to Dr. Dehlendorf, the lesson from such studies is that women are going to assess the importance of the efficacy of their contraceptive method differently, depending on how important it is for them to prevent an unintended pregnancy.
“They’re not going to make a decision about effectiveness the way we as clinicians might think that they should,” she said. “So, assuming that highly effective methods are the best methods for all women because of their effectiveness ignores the variability in preferences, and it also doesn’t take into account women’s strong feelings about other aspects of contraceptive use, such as bleeding profiles and control over their methods.”
Shared decision making may be the best way to help women make a choice based on their preferences. In a study that Dr. Dehlendorf and her associates conducted in 348 women who were seen for contraceptive care in the San Francisco Bay area, two habits were associated with contraceptive continuation: investing in the beginning, and eliciting the patient’s perspective (Am J Obstet Gynecol. 2016 Jul;215[1]:78.e1-9). “Investing in the beginning consists of greeting the patient warmly, making small talk, and treating the patient as a person,” she said. “That was the most highly influential aspect of the interaction. Building rapport and decision support helps women choose a method that’s a good fit for them.
“We also know that women like this method of counseling, but this approach might not be for everyone,” Dr. Dehlendorf cautioned. “Some women don’t want your suggestions, even if it’s grounded in their preferences. They just want to get the method that they came in for. The right thing is to acknowledge that, but you can also ask women if they want to hear about other methods, because some women might not know about all of their options.”
Dr. Dehlendorf reported having no relevant financial disclosures.
AT THE ANNUAL ADVANCES IN INTERNAL MEDICINE
Point/Counterpoint: Is intraoperative drain placement essential during pancreatectomy?
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Temporary tissue expanders optimize radiotherapy after mastectomy
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
AT ASBS 2017
Key clinical point:
Major finding: The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, likely due at least in part to optimal radiotherapy.
Data source: Review of 384 patients.
Disclosures: The investigators said they had no relevant disclosures.
Robotic-assisted IHR causes fewer complications in obese patients
Obese people undergoing inguinal hernia repair experienced fewer complications when the surgery was robotic assisted, compared to open repairs, according to Ramachandra Kolachalam, MD, and his associates.
A total of 148 robotic-assisted repairs (RHRs) and 113 open repairs were included in the study. Of open repair (OHR) patients, 11.5% experienced postoperative complications post discharge, compared with only 2.7% of RHR patients. OHR patients also had lower rates of concomitant procedures (16.8% vs. 29.7%) and bilateral repairs (11.5% vs. 35.1%). Morbidity rates did not differ significantly between the groups.
“Robotic-assisted inguinal hernia repair could lead to increased acceptance of minimally invasive hernia repair with the associated clinical benefits to patients, including those who are obese with higher comorbidities and higher American Surgery Association scores. A prospective study of obesity in RHR is warranted to confirm our findings,” the investigators concluded.
Find the full study in Surgical Endoscopy (2017. doi: 10.1007/s00464-017-5665-z).
Obese people undergoing inguinal hernia repair experienced fewer complications when the surgery was robotic assisted, compared to open repairs, according to Ramachandra Kolachalam, MD, and his associates.
A total of 148 robotic-assisted repairs (RHRs) and 113 open repairs were included in the study. Of open repair (OHR) patients, 11.5% experienced postoperative complications post discharge, compared with only 2.7% of RHR patients. OHR patients also had lower rates of concomitant procedures (16.8% vs. 29.7%) and bilateral repairs (11.5% vs. 35.1%). Morbidity rates did not differ significantly between the groups.
“Robotic-assisted inguinal hernia repair could lead to increased acceptance of minimally invasive hernia repair with the associated clinical benefits to patients, including those who are obese with higher comorbidities and higher American Surgery Association scores. A prospective study of obesity in RHR is warranted to confirm our findings,” the investigators concluded.
Find the full study in Surgical Endoscopy (2017. doi: 10.1007/s00464-017-5665-z).
Obese people undergoing inguinal hernia repair experienced fewer complications when the surgery was robotic assisted, compared to open repairs, according to Ramachandra Kolachalam, MD, and his associates.
A total of 148 robotic-assisted repairs (RHRs) and 113 open repairs were included in the study. Of open repair (OHR) patients, 11.5% experienced postoperative complications post discharge, compared with only 2.7% of RHR patients. OHR patients also had lower rates of concomitant procedures (16.8% vs. 29.7%) and bilateral repairs (11.5% vs. 35.1%). Morbidity rates did not differ significantly between the groups.
“Robotic-assisted inguinal hernia repair could lead to increased acceptance of minimally invasive hernia repair with the associated clinical benefits to patients, including those who are obese with higher comorbidities and higher American Surgery Association scores. A prospective study of obesity in RHR is warranted to confirm our findings,” the investigators concluded.
Find the full study in Surgical Endoscopy (2017. doi: 10.1007/s00464-017-5665-z).
FROM SURGICAL ENDOSCOPY
VA/DOD elevate psychotherapy over medication in updated PTSD guidelines
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – New federal clinical practice guidelines for treating posttraumatic stress disorder move trauma-focused psychotherapy ahead of pharmacotherapy as first-line treatment.
“That is quite a statement that is being made, and it’s a big shift in our treatment guidelines,” Lori L. Davis, MD, said at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. Dr. Davis, who coauthored the update for the Departments of Veterans Affairs and of Defense, discussed the guidelines at the meeting in advance of their release this summer.
The guidelines, dated June 2017 and based on evidence reviewed through March 2016, specify that evidence is strong for first-line psychotherapy that includes some form of exposure and/or cognitive restructuring. Such therapies include prolonged exposure, cognitive processing, eye movement desensitization and reprocessing, narrative exposure therapy, brief eclectic psychotherapy, and PTSD-specific cognitive-behavioral therapy.
The Management of Posttraumatic Stress Work Group found that evidence was weakest for non–trauma-focused therapies, such as stress inoculation training and present-centered and interpersonal psychotherapy. Manualized group therapy also was rated as weak, but insufficient evidence was found to rate one type of group therapy over another.
Insufficient evidence also was cited for psychotherapies not specified in other recommendations, such as dialectical behavior therapy, skills training in affect and interpersonal regulation, acceptance and commitment therapy (ACT), seeking safety therapy, or supportive counseling.
“Some of these treatments have been found to be effective for the treatment of other disorders (e.g., ACT for [major depressive disorder]),” the work group members wrote, “but do not have evidence of efficacy in patients with PTSD.”
The recommendations are based on a review of literature from the past 20 years and are congruent with other treatment guidelines internationally, according to Sheila A.M. Rausch, PhD, who directs mental health research and program evaluation for the VA Ann Arbor Healthcare System in Michigan, is a work group member, and served as a panelist at the meeting.
“What is striking is that, based on people reviewing all the evidence out there – and there are different methodologies for doing so – regardless, [the different groups] tend to come to the same conclusions,” Dr. Rausch said.
The updated guidelines cite insufficient evidence for making any recommendations for augmented or combined treatments of psychotherapy and pharmacotherapy.
Medications considered to have a strong evidence base for monotherapy were sertraline, paroxetine, fluoxetine, and venlafaxine. In cases in which a person declines psychotherapy, those medications are recommended as first-line treatment.
Prazosin, typically used to managing nightmares tied to PTSD, received a “suggest against” recommendation, in part because of the discovery of a publication bias, according to Dr. Davis, who is associate chief of staff for research and development at the Tuscaloosa (Ala.) VA Medical Center and a clinical professor of psychiatry and behavioral neurobiology at the University of Alabama in Birmingham and Tuscaloosa. She noted that the work group remained unsure of “how to grapple with this” news that the study drug did not break from placebo in the treatment of nightmares in more than 300 combat veterans with PTSD.
“We are not trying to tell you not to use antidepressants for major depressive disorder or panic disorders that are often comorbid with PTSD, so you have to keep that in mind as you read these guidelines,” Dr. Davis said. Many patients already take antidepressants because they are easily accessed in primary care practices, she added.
The work group found that evidence generally was weak against atypical antipsychotics – particularly in light of the known adverse side effects of those drugs. However, the group singled out risperidone. “We suggest against treatment of PTSD with quetiapine, olanzapine, and other atypical antipsychotics (except for risperidone, which is a ‘strong against,’ see recommendation 20),” the guidelines suggest.
They also “suggested against” two antidepressants – citalopram and amitriptyline, a tricyclic. The quality of evidence for those drugs was deemed low. Two drugs – lamotrigine and topiramate – also received “suggested against” rankings, and the evidence for the use of those drugs was deemed very low.
Meanwhile, the work group wrote that the quality of evidence was low and “recommended against” the use of three other drugs: divalproex, tiagabine, and guanfacine. They also found the quality of evidence to be very low for the drug class of benzodiazepines and four drugs – risperidone, D-cycloserine, ketamine, and hydrocortisone. They also found insufficient evidence to recommend complementary and integrative health (CIH) practices such as meditation and yoga for treating PTSD. The work group did offer a caveat, however. “It is important to clarify that we are not recommending against the treatments but rather are saying that, at this time, the research does not support the use of any CIH practice for the primary treatment of PTSD.”
Cannabis and its derivatives also were recommended against by the work group because of a “lack of evidence for their efficacy, known adverse effects, and associated risks.”
Dr. Davis said the work group’s findings underscored a crisis in pharmacotherapeutic research in PTSD. Since 2006, there have been only four industry-sponsored drugs for PTSD. “I find it kind of sad,” she said.
Currently, Dr. Rausch’s own study for the VA focuses on comparing the effects of combination therapies for PTSD in the context of patient preferences, in order to tailor the treatments accordingly. In 223 returning veterans with PTSD, she and her colleagues are conducting a head-to-head comparison of prolonged exposure therapy plus placebo, prolonged exposure plus sertraline, and sertraline plus emotion memory management therapy to determine how starting a patient on both kinds of treatments simultaneously affect response.
“It’s clinically important to find out what is really going on in the brain and body,” she said. “Although we know we have therapies that work, we need to find answers for partial responders ... and how to increase the speed and magnitude of response.”
Dr. Davis’s research is funded in part by the VA, Forest, Merck, Tonix, and Otsuka, for whom she also acts as a consultant. Dr. Rausch did not have any disclosures.
[email protected]
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Prior resections increase anastomotic leak risk in Crohn’s
SEATTLE – The risk of anastomotic leaks after bowel resection for Crohn’s disease is more than three times higher in patients who have had prior resections, according to a review of 206 patients at Lahey Hospital and Medical Center in Burlington, Mass.
There were 20 anastomotic leaks within 30 days of resection in those patients, giving an overall leakage rate of 10%. Among the 123 patients who were having their first resection, however, the rate was 5% (6/123). The risk jumped to 17% in the 83 who had prior resections (14/83) and 23% (7) among the 30 patients who had two or more prior resections, which is “substantially higher than we talk about in the clinic when we are counseling these people,” said lead investigator Forrest Johnston, MD, a colorectal surgery fellow at Lahey.
The findings are important because prior resections have not, until now, been formally recognized as a risk factor for anastomotic leaks, and repeat resections are common in Crohn’s. “When you see patients for repeat intestinal resections, you have to look at them as a higher risk population in terms of your counseling and algorithms,” Dr. Johnston said at the American Society of Colon and Rectal Surgeons annual meeting. In addition, to mitigate the increased risk, Crohn’s patients who have repeat resections need additional attention to correct modifiable risk factors before surgery, such as steroid use and malnutrition. “Some of these patients are pushed through the clinic,” but “they deserve a bit more time.”
The heightened risk is also “another factor that might tip you one way or another” in choosing surgical options. “It’s certainly something to think about,” he said.
The new and prior resection patients in the study were well matched in terms of known risk factors for leakage, including age, sex, preoperative serum albumin, and use of immune suppressing medications. “The increased risk of leak is not explained by preoperative nutritional status or medication use,” Dr. Johnston said.
Estimated blood loss, OR time, types of procedures, hand-sewn versus stapled anastomoses, and other surgical variables were also similar.
The lack of significant differences between the groups raises the question of why repeat resections leak more. “That’s the million dollar question. My thought is that repeat resections indicate a greater severity of Crohn’s disease. I think there’s microvascular disease that’s affecting their tissue integrity, but we don’t appreciate it at the time of their anastomosis. If it was obvious at the time of surgery, patients wouldn’t be put together. They’d just get a stoma and be done with it,” Dr. Johnston said
About 80% of both first-time and repeat procedures were ileocolic resections secondary to obstruction, generally without bowel prep. Repeat procedures were performed a mean of 15 years after the first operation. Most initial resections were done laparoscopically, and a good portion of repeat procedures were open. Anorectal cases were excluded from the analysis.
Dr. Johnston said his team looked into the issue after noticing that repeat patients “seemed to leak a little bit more than we expected.”
The investigators had no conflicts of interest.
SEATTLE – The risk of anastomotic leaks after bowel resection for Crohn’s disease is more than three times higher in patients who have had prior resections, according to a review of 206 patients at Lahey Hospital and Medical Center in Burlington, Mass.
There were 20 anastomotic leaks within 30 days of resection in those patients, giving an overall leakage rate of 10%. Among the 123 patients who were having their first resection, however, the rate was 5% (6/123). The risk jumped to 17% in the 83 who had prior resections (14/83) and 23% (7) among the 30 patients who had two or more prior resections, which is “substantially higher than we talk about in the clinic when we are counseling these people,” said lead investigator Forrest Johnston, MD, a colorectal surgery fellow at Lahey.
The findings are important because prior resections have not, until now, been formally recognized as a risk factor for anastomotic leaks, and repeat resections are common in Crohn’s. “When you see patients for repeat intestinal resections, you have to look at them as a higher risk population in terms of your counseling and algorithms,” Dr. Johnston said at the American Society of Colon and Rectal Surgeons annual meeting. In addition, to mitigate the increased risk, Crohn’s patients who have repeat resections need additional attention to correct modifiable risk factors before surgery, such as steroid use and malnutrition. “Some of these patients are pushed through the clinic,” but “they deserve a bit more time.”
The heightened risk is also “another factor that might tip you one way or another” in choosing surgical options. “It’s certainly something to think about,” he said.
The new and prior resection patients in the study were well matched in terms of known risk factors for leakage, including age, sex, preoperative serum albumin, and use of immune suppressing medications. “The increased risk of leak is not explained by preoperative nutritional status or medication use,” Dr. Johnston said.
Estimated blood loss, OR time, types of procedures, hand-sewn versus stapled anastomoses, and other surgical variables were also similar.
The lack of significant differences between the groups raises the question of why repeat resections leak more. “That’s the million dollar question. My thought is that repeat resections indicate a greater severity of Crohn’s disease. I think there’s microvascular disease that’s affecting their tissue integrity, but we don’t appreciate it at the time of their anastomosis. If it was obvious at the time of surgery, patients wouldn’t be put together. They’d just get a stoma and be done with it,” Dr. Johnston said
About 80% of both first-time and repeat procedures were ileocolic resections secondary to obstruction, generally without bowel prep. Repeat procedures were performed a mean of 15 years after the first operation. Most initial resections were done laparoscopically, and a good portion of repeat procedures were open. Anorectal cases were excluded from the analysis.
Dr. Johnston said his team looked into the issue after noticing that repeat patients “seemed to leak a little bit more than we expected.”
The investigators had no conflicts of interest.
SEATTLE – The risk of anastomotic leaks after bowel resection for Crohn’s disease is more than three times higher in patients who have had prior resections, according to a review of 206 patients at Lahey Hospital and Medical Center in Burlington, Mass.
There were 20 anastomotic leaks within 30 days of resection in those patients, giving an overall leakage rate of 10%. Among the 123 patients who were having their first resection, however, the rate was 5% (6/123). The risk jumped to 17% in the 83 who had prior resections (14/83) and 23% (7) among the 30 patients who had two or more prior resections, which is “substantially higher than we talk about in the clinic when we are counseling these people,” said lead investigator Forrest Johnston, MD, a colorectal surgery fellow at Lahey.
The findings are important because prior resections have not, until now, been formally recognized as a risk factor for anastomotic leaks, and repeat resections are common in Crohn’s. “When you see patients for repeat intestinal resections, you have to look at them as a higher risk population in terms of your counseling and algorithms,” Dr. Johnston said at the American Society of Colon and Rectal Surgeons annual meeting. In addition, to mitigate the increased risk, Crohn’s patients who have repeat resections need additional attention to correct modifiable risk factors before surgery, such as steroid use and malnutrition. “Some of these patients are pushed through the clinic,” but “they deserve a bit more time.”
The heightened risk is also “another factor that might tip you one way or another” in choosing surgical options. “It’s certainly something to think about,” he said.
The new and prior resection patients in the study were well matched in terms of known risk factors for leakage, including age, sex, preoperative serum albumin, and use of immune suppressing medications. “The increased risk of leak is not explained by preoperative nutritional status or medication use,” Dr. Johnston said.
Estimated blood loss, OR time, types of procedures, hand-sewn versus stapled anastomoses, and other surgical variables were also similar.
The lack of significant differences between the groups raises the question of why repeat resections leak more. “That’s the million dollar question. My thought is that repeat resections indicate a greater severity of Crohn’s disease. I think there’s microvascular disease that’s affecting their tissue integrity, but we don’t appreciate it at the time of their anastomosis. If it was obvious at the time of surgery, patients wouldn’t be put together. They’d just get a stoma and be done with it,” Dr. Johnston said
About 80% of both first-time and repeat procedures were ileocolic resections secondary to obstruction, generally without bowel prep. Repeat procedures were performed a mean of 15 years after the first operation. Most initial resections were done laparoscopically, and a good portion of repeat procedures were open. Anorectal cases were excluded from the analysis.
Dr. Johnston said his team looked into the issue after noticing that repeat patients “seemed to leak a little bit more than we expected.”
The investigators had no conflicts of interest.
AT ASCRS 2017
Key clinical point:
Major finding: The number of prior resections correlated almost perfectly with an increasing risk of anastomotic leakage (r = 0.998); the odds ratio for leakage with prior resection, compared with initial resection, was 3.5 (95% confidence interval, 1.3-9.4; P less than .005).
Data source: A review of 206 Crohn’ patients.
Disclosures: The investigators had no conflicts of interest.