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Low-dose FVIII prophylaxis reduced bleeding in hemophilia A
The findings have implications for low resource countries, the researchers reported.
Novie A. Chozie, MD, of Universitas Indonesia in Jakarta, along with colleagues, conducted a parallel-group, randomized controlled study of 50 children with severe hemophilia A. Study participants were randomized to receive either low‐dose FVIII prophylaxis (n = 25) or on‐demand treatment (n = 25) for a total of 12 months. The findings were published in Haemophilia.
Participants in the prophylaxis arm received FVIII at a dose of 10 IU/kg, infused twice weekly. If patients experienced an episode of acute bleeding, prophylaxis was delayed until the episode resolved.
The primary outcome was the number of total and joint bleeding events from the start of therapy to 12 months. Secondary outcomes included evidence of FVIII inhibitor, Hemophilia Joint Health Score (HJHS), and Hemophilia Early Arthropathy Detection Ultrasound (HEAD‐US) score.
After analysis, the team found that the number of joint and total bleeding events was significantly lower in the prophylaxis group. For total bleeding events, there was a median of 8 events with the prophylaxis group, compared with 25 in the on-demand treatment group (P less than .001). There was a median of three joint bleeding events in the prophylaxis group versus nine in the on-demand group (P less than .001).
Patients in the prophylaxis arm also showed improved joint function (P = .004), while those in the on‐demand arm showed evidence of deterioration (P = .001).
Two key limitations of the study were short duration of follow-up and single‐center design, which could have limited the generalizability of the results.
“In countries with limited resources, low‐dose prophylaxis is strongly recommended as a therapeutic option for severe haemophilia A [in] children,” the researchers wrote.
The study was funded by Grifols. The authors reported having no conflicts of interest.
SOURCE: Chozie NA et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13770.
The findings have implications for low resource countries, the researchers reported.
Novie A. Chozie, MD, of Universitas Indonesia in Jakarta, along with colleagues, conducted a parallel-group, randomized controlled study of 50 children with severe hemophilia A. Study participants were randomized to receive either low‐dose FVIII prophylaxis (n = 25) or on‐demand treatment (n = 25) for a total of 12 months. The findings were published in Haemophilia.
Participants in the prophylaxis arm received FVIII at a dose of 10 IU/kg, infused twice weekly. If patients experienced an episode of acute bleeding, prophylaxis was delayed until the episode resolved.
The primary outcome was the number of total and joint bleeding events from the start of therapy to 12 months. Secondary outcomes included evidence of FVIII inhibitor, Hemophilia Joint Health Score (HJHS), and Hemophilia Early Arthropathy Detection Ultrasound (HEAD‐US) score.
After analysis, the team found that the number of joint and total bleeding events was significantly lower in the prophylaxis group. For total bleeding events, there was a median of 8 events with the prophylaxis group, compared with 25 in the on-demand treatment group (P less than .001). There was a median of three joint bleeding events in the prophylaxis group versus nine in the on-demand group (P less than .001).
Patients in the prophylaxis arm also showed improved joint function (P = .004), while those in the on‐demand arm showed evidence of deterioration (P = .001).
Two key limitations of the study were short duration of follow-up and single‐center design, which could have limited the generalizability of the results.
“In countries with limited resources, low‐dose prophylaxis is strongly recommended as a therapeutic option for severe haemophilia A [in] children,” the researchers wrote.
The study was funded by Grifols. The authors reported having no conflicts of interest.
SOURCE: Chozie NA et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13770.
The findings have implications for low resource countries, the researchers reported.
Novie A. Chozie, MD, of Universitas Indonesia in Jakarta, along with colleagues, conducted a parallel-group, randomized controlled study of 50 children with severe hemophilia A. Study participants were randomized to receive either low‐dose FVIII prophylaxis (n = 25) or on‐demand treatment (n = 25) for a total of 12 months. The findings were published in Haemophilia.
Participants in the prophylaxis arm received FVIII at a dose of 10 IU/kg, infused twice weekly. If patients experienced an episode of acute bleeding, prophylaxis was delayed until the episode resolved.
The primary outcome was the number of total and joint bleeding events from the start of therapy to 12 months. Secondary outcomes included evidence of FVIII inhibitor, Hemophilia Joint Health Score (HJHS), and Hemophilia Early Arthropathy Detection Ultrasound (HEAD‐US) score.
After analysis, the team found that the number of joint and total bleeding events was significantly lower in the prophylaxis group. For total bleeding events, there was a median of 8 events with the prophylaxis group, compared with 25 in the on-demand treatment group (P less than .001). There was a median of three joint bleeding events in the prophylaxis group versus nine in the on-demand group (P less than .001).
Patients in the prophylaxis arm also showed improved joint function (P = .004), while those in the on‐demand arm showed evidence of deterioration (P = .001).
Two key limitations of the study were short duration of follow-up and single‐center design, which could have limited the generalizability of the results.
“In countries with limited resources, low‐dose prophylaxis is strongly recommended as a therapeutic option for severe haemophilia A [in] children,” the researchers wrote.
The study was funded by Grifols. The authors reported having no conflicts of interest.
SOURCE: Chozie NA et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13770.
FROM HAEMOPHILIA
Navigating racism while in medical training
SAN FRANCISCO – When Jessica Isom, MD, MPH, and her colleagues noticed the absence of good role modeling about how to address race and racism in interactions with supervisors at their long-term care clinic, they conducted a research study.
“Now, we’re working on rolling out what those solutions might be for addressing this gap in the education,” said Dr. Isom, a PGY-4 resident at Yale University, New Haven, Conn. Many of the issues Dr. Isom and her colleagues found are reminiscent of those identified almost 50 years ago by Billy E. Jones, MD, and his colleagues. Their article (1970 Dec; 127[6]:798-803) focusing on the problems of black residents in predominantly white institutions was published in the American Journal of Psychiatry, Constance E. Dunlap, MD, said at the annual meeting of the American Psychiatric Association.
In this video, Dr. Dunlap interviews Dr. Isom about her experiences with both supervisors and patients on issues tied to race and racism – and examines possible solutions.
In one case, Dr. Isom said she created an opening for discussion with a supervisor by advising him to read the book White Fragility (Beacon Press, 2018). “He read the book,” Dr. Isom said. “And And he’s thinking about these things now as a white man and his relationship to racism. So that’s sort of a positive outcome from having that conversation in the first place.”
In another case involving a patient who declined treatment from Dr. Isom and an Asian male medical student, Dr. Isom said she respected the patient’s wishes and walked out of the room. When she shared the experience with her team, the incident was not addressed.
Dr. Isom’s experiences reflects that of African Americans and other ethnic minorities in the United States, Dr. Dunlap said. “I think about being in junior high school and reading ... and doing my own study outside of school and that has carried through college, medical school, and even in residency – and definitely psychoanalytic training – where psychoanalysts like Frantz Fanon, Frances Cress Welsing, even Dorothy Holmes ... were not included in the mainstream curriculum.” However, those thinkers are included in some curricula now.
“This is an example of how medicine and psychoanalysis have been functioning in parallel with the way the country functions,” Dr. Dunlap said. “This is a huge blind spot.”
Dr. Isom worked on the research study with fellow residents* Myra Mathis, MD; Flavia DeSouza, MHS, MD; and Natalie Lastra, MD. Dr. Isom is member of the American Psychiatric Association Assembly as the area 1 representative for resident fellow members. She also is one of the chief residents of diversity and inclusion, and a codirector of the social justice and health equity curriculum at the department of psychiatry at Yale. Dr. Dunlap is a psychiatrist and psychoanalyst with more than 25 years’ experience in clinical care, psychiatric education, patient advocacy, and community outreach. She is a member of the APA assembly representing the Washington Psychiatric Society. Dr. Isom and Dr. Dunlap had no disclosures.
*CLARIFICATION, 5/22/2019
SAN FRANCISCO – When Jessica Isom, MD, MPH, and her colleagues noticed the absence of good role modeling about how to address race and racism in interactions with supervisors at their long-term care clinic, they conducted a research study.
“Now, we’re working on rolling out what those solutions might be for addressing this gap in the education,” said Dr. Isom, a PGY-4 resident at Yale University, New Haven, Conn. Many of the issues Dr. Isom and her colleagues found are reminiscent of those identified almost 50 years ago by Billy E. Jones, MD, and his colleagues. Their article (1970 Dec; 127[6]:798-803) focusing on the problems of black residents in predominantly white institutions was published in the American Journal of Psychiatry, Constance E. Dunlap, MD, said at the annual meeting of the American Psychiatric Association.
In this video, Dr. Dunlap interviews Dr. Isom about her experiences with both supervisors and patients on issues tied to race and racism – and examines possible solutions.
In one case, Dr. Isom said she created an opening for discussion with a supervisor by advising him to read the book White Fragility (Beacon Press, 2018). “He read the book,” Dr. Isom said. “And And he’s thinking about these things now as a white man and his relationship to racism. So that’s sort of a positive outcome from having that conversation in the first place.”
In another case involving a patient who declined treatment from Dr. Isom and an Asian male medical student, Dr. Isom said she respected the patient’s wishes and walked out of the room. When she shared the experience with her team, the incident was not addressed.
Dr. Isom’s experiences reflects that of African Americans and other ethnic minorities in the United States, Dr. Dunlap said. “I think about being in junior high school and reading ... and doing my own study outside of school and that has carried through college, medical school, and even in residency – and definitely psychoanalytic training – where psychoanalysts like Frantz Fanon, Frances Cress Welsing, even Dorothy Holmes ... were not included in the mainstream curriculum.” However, those thinkers are included in some curricula now.
“This is an example of how medicine and psychoanalysis have been functioning in parallel with the way the country functions,” Dr. Dunlap said. “This is a huge blind spot.”
Dr. Isom worked on the research study with fellow residents* Myra Mathis, MD; Flavia DeSouza, MHS, MD; and Natalie Lastra, MD. Dr. Isom is member of the American Psychiatric Association Assembly as the area 1 representative for resident fellow members. She also is one of the chief residents of diversity and inclusion, and a codirector of the social justice and health equity curriculum at the department of psychiatry at Yale. Dr. Dunlap is a psychiatrist and psychoanalyst with more than 25 years’ experience in clinical care, psychiatric education, patient advocacy, and community outreach. She is a member of the APA assembly representing the Washington Psychiatric Society. Dr. Isom and Dr. Dunlap had no disclosures.
*CLARIFICATION, 5/22/2019
SAN FRANCISCO – When Jessica Isom, MD, MPH, and her colleagues noticed the absence of good role modeling about how to address race and racism in interactions with supervisors at their long-term care clinic, they conducted a research study.
“Now, we’re working on rolling out what those solutions might be for addressing this gap in the education,” said Dr. Isom, a PGY-4 resident at Yale University, New Haven, Conn. Many of the issues Dr. Isom and her colleagues found are reminiscent of those identified almost 50 years ago by Billy E. Jones, MD, and his colleagues. Their article (1970 Dec; 127[6]:798-803) focusing on the problems of black residents in predominantly white institutions was published in the American Journal of Psychiatry, Constance E. Dunlap, MD, said at the annual meeting of the American Psychiatric Association.
In this video, Dr. Dunlap interviews Dr. Isom about her experiences with both supervisors and patients on issues tied to race and racism – and examines possible solutions.
In one case, Dr. Isom said she created an opening for discussion with a supervisor by advising him to read the book White Fragility (Beacon Press, 2018). “He read the book,” Dr. Isom said. “And And he’s thinking about these things now as a white man and his relationship to racism. So that’s sort of a positive outcome from having that conversation in the first place.”
In another case involving a patient who declined treatment from Dr. Isom and an Asian male medical student, Dr. Isom said she respected the patient’s wishes and walked out of the room. When she shared the experience with her team, the incident was not addressed.
Dr. Isom’s experiences reflects that of African Americans and other ethnic minorities in the United States, Dr. Dunlap said. “I think about being in junior high school and reading ... and doing my own study outside of school and that has carried through college, medical school, and even in residency – and definitely psychoanalytic training – where psychoanalysts like Frantz Fanon, Frances Cress Welsing, even Dorothy Holmes ... were not included in the mainstream curriculum.” However, those thinkers are included in some curricula now.
“This is an example of how medicine and psychoanalysis have been functioning in parallel with the way the country functions,” Dr. Dunlap said. “This is a huge blind spot.”
Dr. Isom worked on the research study with fellow residents* Myra Mathis, MD; Flavia DeSouza, MHS, MD; and Natalie Lastra, MD. Dr. Isom is member of the American Psychiatric Association Assembly as the area 1 representative for resident fellow members. She also is one of the chief residents of diversity and inclusion, and a codirector of the social justice and health equity curriculum at the department of psychiatry at Yale. Dr. Dunlap is a psychiatrist and psychoanalyst with more than 25 years’ experience in clinical care, psychiatric education, patient advocacy, and community outreach. She is a member of the APA assembly representing the Washington Psychiatric Society. Dr. Isom and Dr. Dunlap had no disclosures.
*CLARIFICATION, 5/22/2019
REPORTING FROM APA 2019
Acting up at APA
SAN FRANCISCO – A number of years ago, Anne Hanson, Steve Daviss, and I worked together on a psychiatry podcast called “My Three Shrinks.” In the course of making the podcast, Dr. Daviss suggested the three of us should take an improv class together – he felt it would help us blend together better as we interacted to create these dialogues.
We met on Sunday afternoons around one of our dining room tables, often with chili and beer, sometimes with guest psychiatrists, and over the course of a few years, we produced 70 episodes. But we never did take that improv class together.
Steve conveyed that in improv, it’s bad to say, “No, but ...” and instead, one should say, “Yes, and ...” to build upon a theme while working in concert with others. With this limited background, I decided that at this year’s American Psychiatric Association meeting in San Francisco I would report on a session called “You Are Human: Addressing Burnout Through Improv,” organized by Tristan Gorrindo, MD, the director of education and deputy medical director for the APA, and Ashley Whitehurst, a program manager in continuing medical education and faculty at the Second City Training Center, a Chicago-based comedy institution. The session was held on Tuesday morning and was attended by psychiatrists of all training levels. Name badges revealed that attendees were from across the United States and from Canada, Mexico, and one psychiatrist from South Africa.
Before I write about the session on using improv to address physician burnout, I’d like to back up a day, as this was not the first session I found at APA where people were acting out! On Monday, I had gone to a workshop called “Inside OCD: I Am Not My Illness.” I went with the hope of learning something about obsessive-compulsive disorder that I could use to help my patients who suffer from this disorder, with no intention of writing about the session. I was running quite late and chose the session based solely on the title. I stumbled into a rather unusual venue: Patients with OCD were putting on a performance where they discussed how it was to live with the symptoms of this disabling illness, stretched into a humorous storytelling adventure.
The performance group, a joint venture of the Center for Arts in Medicine at the University of Florida in partnership with University of Florida Center for OCD, Anxiety, & Related Disorders consisted of patients who came together in a 10-week course with an acting coach, a resident psychiatrist who participated with the group, and the oversight of their attending psychiatrist, Carol Mathews, MD, to create this collaborative and moving theatrical performance. The group performed, then talked about how this endeavor had helped them to share their stories, to grow in their self-acceptance and self-confidence, and to enjoy a sense of community, and escape from shame and loneliness.
On Monday, I went from the OCD theater to a session called “Unscripting: Using Improvisational Theatre to Move Beyond Personal Limitations.” This workshop was led by Jeffrey Katzman, MD, a psychiatrist who practices in Albuquerque, N.M., and coauthor of “Life Unscripted: Using Improv Principles to Get Unstuck, Boost Confidence, and Transform Your Life.” Dr. Katzman referenced how improv requires the participants to collaborate and respond to one another in ways that are not unlike what occurs in psychotherapy.
“It’s about two people listening to each other, reacting to each other, and ultimately regulating one another.”
A second speaker, Peter Felsman, PhD, LMSW, presented his doctoral dissertation work looking at how improv classes might impact teens with anxiety disorders.
It was at this session that I had my first experiences actually doing some improv exercises. “Improv involves increasing your uncertainty tolerance,” Dr. Katzman noted. “The available scripts are much broader than what you are used to, and they increase the sense of autonomy.” Participants were challenged to work at mirroring the actions of a partner, of switching who was leading in these exercises, and of telling stories where we built upon what the last person gave to the tale by adding unpredictable paths of plot development.
The Tuesday morning session was longer; it lasted from 8 a.m. to 11 a.m. I arrived early, and the first name tag I saw was that of Steven Reidbord, MD, a psychiatrist in San Francisco whom I had never met, but with whom I had interacted many times over the years as we both have had psychiatry blogs. I was delighted as I started the session. Dr. Gorrindo started the symposium by defining physician burnout and discussing how our current system fuels burnout. He discussed his own interest in improv and its use to foster more creative, flexible, and collaborative responses.
Ashley Whitehurst then led the participants in a series of exercises. We walked around the room taking unscripted turns yelling out “I am a star” while the rest of the participants clustered around to frame each individual star! We took partners and discussed a toy each of us had longed for and never gotten in childhood, then created a fictional toy as conglomerate of those toys never received. This light exercise included conversations about the sadness of the toys longed for and the disappointments we’d suffered. One psychiatrist felt gratitude: She had received most of the toys she’d wanted. There were others who’d wanted a real pony or a real typewriter, only to be gifted with disappointing plastic versions. One gentleman longed for a sibling who had died before he had even been born; there were no toys for this space.
Our circle conversations moved into tales we created by interrupting one another with our associations about what we loved and hated; there was the annoyance of having sand in your underwear and superheros who deliver ice cream. We all talked about what it involved to let go of our own agendas and fold into what was going on in the moment, to sway with a plot that changed as soon as it was formed, to function with rules so different from what we were used to. We discussed how improv might be useful in teaching trainees.
“This was interesting and different,” said Sergio Lobato, MD, a psychiatrist from Tijuana, Mexico, who retired after more than 30 years of working in a government hospital. “I saw 20 to 30 patients a day, and there was some burnout. I’m here at the meeting and trying to learn things to help my daughter, who is in her third year of psychiatry training.”
Ms. Whitehurst, our improv instructor, has done many of these workshops with people of all ages and with other groups of physicians. “When people sign up for improv classes, they usually have some idea what they are getting into. With doctors at a conference, it takes just a little longer for them to let their guard down. Improv is an art form and a way to create, it’s a great equalizer and I’ve noticed an evolution in myself as it has changed how I interact. ”
Veronica Samet, a PGY-4 resident from Emory University, Atlanta, added: “In psychiatry, we are taught to leave space in the room for the other person. You get used to compressing yourself into something neutral and it’s hard not to bring that state home. This experience was revitalizing!”
I was delighted to find a friend when I walked into the morning symposium and by the time I left, I felt like I’d made a roomful of friends. We’d played games and I was completely consumed by the tasks at hand. We talked about how each game made us feel, and in some ways this was not all that far off from work as a psychiatrist – the humor and fun were on the surface, but ... or rather, “ ... yes, and” the stories that went along with what we did made for a moment of connection in a whole new way.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice in Baltimore.
SAN FRANCISCO – A number of years ago, Anne Hanson, Steve Daviss, and I worked together on a psychiatry podcast called “My Three Shrinks.” In the course of making the podcast, Dr. Daviss suggested the three of us should take an improv class together – he felt it would help us blend together better as we interacted to create these dialogues.
We met on Sunday afternoons around one of our dining room tables, often with chili and beer, sometimes with guest psychiatrists, and over the course of a few years, we produced 70 episodes. But we never did take that improv class together.
Steve conveyed that in improv, it’s bad to say, “No, but ...” and instead, one should say, “Yes, and ...” to build upon a theme while working in concert with others. With this limited background, I decided that at this year’s American Psychiatric Association meeting in San Francisco I would report on a session called “You Are Human: Addressing Burnout Through Improv,” organized by Tristan Gorrindo, MD, the director of education and deputy medical director for the APA, and Ashley Whitehurst, a program manager in continuing medical education and faculty at the Second City Training Center, a Chicago-based comedy institution. The session was held on Tuesday morning and was attended by psychiatrists of all training levels. Name badges revealed that attendees were from across the United States and from Canada, Mexico, and one psychiatrist from South Africa.
Before I write about the session on using improv to address physician burnout, I’d like to back up a day, as this was not the first session I found at APA where people were acting out! On Monday, I had gone to a workshop called “Inside OCD: I Am Not My Illness.” I went with the hope of learning something about obsessive-compulsive disorder that I could use to help my patients who suffer from this disorder, with no intention of writing about the session. I was running quite late and chose the session based solely on the title. I stumbled into a rather unusual venue: Patients with OCD were putting on a performance where they discussed how it was to live with the symptoms of this disabling illness, stretched into a humorous storytelling adventure.
The performance group, a joint venture of the Center for Arts in Medicine at the University of Florida in partnership with University of Florida Center for OCD, Anxiety, & Related Disorders consisted of patients who came together in a 10-week course with an acting coach, a resident psychiatrist who participated with the group, and the oversight of their attending psychiatrist, Carol Mathews, MD, to create this collaborative and moving theatrical performance. The group performed, then talked about how this endeavor had helped them to share their stories, to grow in their self-acceptance and self-confidence, and to enjoy a sense of community, and escape from shame and loneliness.
On Monday, I went from the OCD theater to a session called “Unscripting: Using Improvisational Theatre to Move Beyond Personal Limitations.” This workshop was led by Jeffrey Katzman, MD, a psychiatrist who practices in Albuquerque, N.M., and coauthor of “Life Unscripted: Using Improv Principles to Get Unstuck, Boost Confidence, and Transform Your Life.” Dr. Katzman referenced how improv requires the participants to collaborate and respond to one another in ways that are not unlike what occurs in psychotherapy.
“It’s about two people listening to each other, reacting to each other, and ultimately regulating one another.”
A second speaker, Peter Felsman, PhD, LMSW, presented his doctoral dissertation work looking at how improv classes might impact teens with anxiety disorders.
It was at this session that I had my first experiences actually doing some improv exercises. “Improv involves increasing your uncertainty tolerance,” Dr. Katzman noted. “The available scripts are much broader than what you are used to, and they increase the sense of autonomy.” Participants were challenged to work at mirroring the actions of a partner, of switching who was leading in these exercises, and of telling stories where we built upon what the last person gave to the tale by adding unpredictable paths of plot development.
The Tuesday morning session was longer; it lasted from 8 a.m. to 11 a.m. I arrived early, and the first name tag I saw was that of Steven Reidbord, MD, a psychiatrist in San Francisco whom I had never met, but with whom I had interacted many times over the years as we both have had psychiatry blogs. I was delighted as I started the session. Dr. Gorrindo started the symposium by defining physician burnout and discussing how our current system fuels burnout. He discussed his own interest in improv and its use to foster more creative, flexible, and collaborative responses.
Ashley Whitehurst then led the participants in a series of exercises. We walked around the room taking unscripted turns yelling out “I am a star” while the rest of the participants clustered around to frame each individual star! We took partners and discussed a toy each of us had longed for and never gotten in childhood, then created a fictional toy as conglomerate of those toys never received. This light exercise included conversations about the sadness of the toys longed for and the disappointments we’d suffered. One psychiatrist felt gratitude: She had received most of the toys she’d wanted. There were others who’d wanted a real pony or a real typewriter, only to be gifted with disappointing plastic versions. One gentleman longed for a sibling who had died before he had even been born; there were no toys for this space.
Our circle conversations moved into tales we created by interrupting one another with our associations about what we loved and hated; there was the annoyance of having sand in your underwear and superheros who deliver ice cream. We all talked about what it involved to let go of our own agendas and fold into what was going on in the moment, to sway with a plot that changed as soon as it was formed, to function with rules so different from what we were used to. We discussed how improv might be useful in teaching trainees.
“This was interesting and different,” said Sergio Lobato, MD, a psychiatrist from Tijuana, Mexico, who retired after more than 30 years of working in a government hospital. “I saw 20 to 30 patients a day, and there was some burnout. I’m here at the meeting and trying to learn things to help my daughter, who is in her third year of psychiatry training.”
Ms. Whitehurst, our improv instructor, has done many of these workshops with people of all ages and with other groups of physicians. “When people sign up for improv classes, they usually have some idea what they are getting into. With doctors at a conference, it takes just a little longer for them to let their guard down. Improv is an art form and a way to create, it’s a great equalizer and I’ve noticed an evolution in myself as it has changed how I interact. ”
Veronica Samet, a PGY-4 resident from Emory University, Atlanta, added: “In psychiatry, we are taught to leave space in the room for the other person. You get used to compressing yourself into something neutral and it’s hard not to bring that state home. This experience was revitalizing!”
I was delighted to find a friend when I walked into the morning symposium and by the time I left, I felt like I’d made a roomful of friends. We’d played games and I was completely consumed by the tasks at hand. We talked about how each game made us feel, and in some ways this was not all that far off from work as a psychiatrist – the humor and fun were on the surface, but ... or rather, “ ... yes, and” the stories that went along with what we did made for a moment of connection in a whole new way.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice in Baltimore.
SAN FRANCISCO – A number of years ago, Anne Hanson, Steve Daviss, and I worked together on a psychiatry podcast called “My Three Shrinks.” In the course of making the podcast, Dr. Daviss suggested the three of us should take an improv class together – he felt it would help us blend together better as we interacted to create these dialogues.
We met on Sunday afternoons around one of our dining room tables, often with chili and beer, sometimes with guest psychiatrists, and over the course of a few years, we produced 70 episodes. But we never did take that improv class together.
Steve conveyed that in improv, it’s bad to say, “No, but ...” and instead, one should say, “Yes, and ...” to build upon a theme while working in concert with others. With this limited background, I decided that at this year’s American Psychiatric Association meeting in San Francisco I would report on a session called “You Are Human: Addressing Burnout Through Improv,” organized by Tristan Gorrindo, MD, the director of education and deputy medical director for the APA, and Ashley Whitehurst, a program manager in continuing medical education and faculty at the Second City Training Center, a Chicago-based comedy institution. The session was held on Tuesday morning and was attended by psychiatrists of all training levels. Name badges revealed that attendees were from across the United States and from Canada, Mexico, and one psychiatrist from South Africa.
Before I write about the session on using improv to address physician burnout, I’d like to back up a day, as this was not the first session I found at APA where people were acting out! On Monday, I had gone to a workshop called “Inside OCD: I Am Not My Illness.” I went with the hope of learning something about obsessive-compulsive disorder that I could use to help my patients who suffer from this disorder, with no intention of writing about the session. I was running quite late and chose the session based solely on the title. I stumbled into a rather unusual venue: Patients with OCD were putting on a performance where they discussed how it was to live with the symptoms of this disabling illness, stretched into a humorous storytelling adventure.
The performance group, a joint venture of the Center for Arts in Medicine at the University of Florida in partnership with University of Florida Center for OCD, Anxiety, & Related Disorders consisted of patients who came together in a 10-week course with an acting coach, a resident psychiatrist who participated with the group, and the oversight of their attending psychiatrist, Carol Mathews, MD, to create this collaborative and moving theatrical performance. The group performed, then talked about how this endeavor had helped them to share their stories, to grow in their self-acceptance and self-confidence, and to enjoy a sense of community, and escape from shame and loneliness.
On Monday, I went from the OCD theater to a session called “Unscripting: Using Improvisational Theatre to Move Beyond Personal Limitations.” This workshop was led by Jeffrey Katzman, MD, a psychiatrist who practices in Albuquerque, N.M., and coauthor of “Life Unscripted: Using Improv Principles to Get Unstuck, Boost Confidence, and Transform Your Life.” Dr. Katzman referenced how improv requires the participants to collaborate and respond to one another in ways that are not unlike what occurs in psychotherapy.
“It’s about two people listening to each other, reacting to each other, and ultimately regulating one another.”
A second speaker, Peter Felsman, PhD, LMSW, presented his doctoral dissertation work looking at how improv classes might impact teens with anxiety disorders.
It was at this session that I had my first experiences actually doing some improv exercises. “Improv involves increasing your uncertainty tolerance,” Dr. Katzman noted. “The available scripts are much broader than what you are used to, and they increase the sense of autonomy.” Participants were challenged to work at mirroring the actions of a partner, of switching who was leading in these exercises, and of telling stories where we built upon what the last person gave to the tale by adding unpredictable paths of plot development.
The Tuesday morning session was longer; it lasted from 8 a.m. to 11 a.m. I arrived early, and the first name tag I saw was that of Steven Reidbord, MD, a psychiatrist in San Francisco whom I had never met, but with whom I had interacted many times over the years as we both have had psychiatry blogs. I was delighted as I started the session. Dr. Gorrindo started the symposium by defining physician burnout and discussing how our current system fuels burnout. He discussed his own interest in improv and its use to foster more creative, flexible, and collaborative responses.
Ashley Whitehurst then led the participants in a series of exercises. We walked around the room taking unscripted turns yelling out “I am a star” while the rest of the participants clustered around to frame each individual star! We took partners and discussed a toy each of us had longed for and never gotten in childhood, then created a fictional toy as conglomerate of those toys never received. This light exercise included conversations about the sadness of the toys longed for and the disappointments we’d suffered. One psychiatrist felt gratitude: She had received most of the toys she’d wanted. There were others who’d wanted a real pony or a real typewriter, only to be gifted with disappointing plastic versions. One gentleman longed for a sibling who had died before he had even been born; there were no toys for this space.
Our circle conversations moved into tales we created by interrupting one another with our associations about what we loved and hated; there was the annoyance of having sand in your underwear and superheros who deliver ice cream. We all talked about what it involved to let go of our own agendas and fold into what was going on in the moment, to sway with a plot that changed as soon as it was formed, to function with rules so different from what we were used to. We discussed how improv might be useful in teaching trainees.
“This was interesting and different,” said Sergio Lobato, MD, a psychiatrist from Tijuana, Mexico, who retired after more than 30 years of working in a government hospital. “I saw 20 to 30 patients a day, and there was some burnout. I’m here at the meeting and trying to learn things to help my daughter, who is in her third year of psychiatry training.”
Ms. Whitehurst, our improv instructor, has done many of these workshops with people of all ages and with other groups of physicians. “When people sign up for improv classes, they usually have some idea what they are getting into. With doctors at a conference, it takes just a little longer for them to let their guard down. Improv is an art form and a way to create, it’s a great equalizer and I’ve noticed an evolution in myself as it has changed how I interact. ”
Veronica Samet, a PGY-4 resident from Emory University, Atlanta, added: “In psychiatry, we are taught to leave space in the room for the other person. You get used to compressing yourself into something neutral and it’s hard not to bring that state home. This experience was revitalizing!”
I was delighted to find a friend when I walked into the morning symposium and by the time I left, I felt like I’d made a roomful of friends. We’d played games and I was completely consumed by the tasks at hand. We talked about how each game made us feel, and in some ways this was not all that far off from work as a psychiatrist – the humor and fun were on the surface, but ... or rather, “ ... yes, and” the stories that went along with what we did made for a moment of connection in a whole new way.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice in Baltimore.
FDA panel to reassess the fate of paclitaxel-coated PAD devices
The Food and Drug Administration (FDA) announced that the Circulatory System Devices Panel of the Medical Devices Advisory Committee will meet June 19-20, 2019, at the Gaithersburg Holiday Inn, Gaithersburg, Md., to “discuss and make recommendations on information related to recent observations of increased compared to patients treated with uncoated comparator devices.”
The FDA is requesting the panel’s input “regarding the presence and magnitude of the signal and potential causes.” In addition, the FDA will seek input “regarding appropriate regulatory actions associated with the findings.”
In a Letter to Healthcare Providers issued March 15, the FDA reported that their preliminary review of these data found “a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products, compared to patients treated with uncoated devices.”
Their recommendation was: “Alternative treatment options should generally be used for most patients,” rather than paclitaxel-coated balloons and stents for peripheral arterial disease (PAD), pending the above announced ongoing safety review.
The FDA intends to make background material available to the public no later than 2 business days before the meeting on its website at the appropriate advisory committee meeting link.
The Food and Drug Administration (FDA) announced that the Circulatory System Devices Panel of the Medical Devices Advisory Committee will meet June 19-20, 2019, at the Gaithersburg Holiday Inn, Gaithersburg, Md., to “discuss and make recommendations on information related to recent observations of increased compared to patients treated with uncoated comparator devices.”
The FDA is requesting the panel’s input “regarding the presence and magnitude of the signal and potential causes.” In addition, the FDA will seek input “regarding appropriate regulatory actions associated with the findings.”
In a Letter to Healthcare Providers issued March 15, the FDA reported that their preliminary review of these data found “a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products, compared to patients treated with uncoated devices.”
Their recommendation was: “Alternative treatment options should generally be used for most patients,” rather than paclitaxel-coated balloons and stents for peripheral arterial disease (PAD), pending the above announced ongoing safety review.
The FDA intends to make background material available to the public no later than 2 business days before the meeting on its website at the appropriate advisory committee meeting link.
The Food and Drug Administration (FDA) announced that the Circulatory System Devices Panel of the Medical Devices Advisory Committee will meet June 19-20, 2019, at the Gaithersburg Holiday Inn, Gaithersburg, Md., to “discuss and make recommendations on information related to recent observations of increased compared to patients treated with uncoated comparator devices.”
The FDA is requesting the panel’s input “regarding the presence and magnitude of the signal and potential causes.” In addition, the FDA will seek input “regarding appropriate regulatory actions associated with the findings.”
In a Letter to Healthcare Providers issued March 15, the FDA reported that their preliminary review of these data found “a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products, compared to patients treated with uncoated devices.”
Their recommendation was: “Alternative treatment options should generally be used for most patients,” rather than paclitaxel-coated balloons and stents for peripheral arterial disease (PAD), pending the above announced ongoing safety review.
The FDA intends to make background material available to the public no later than 2 business days before the meeting on its website at the appropriate advisory committee meeting link.
Despite HCV cure, liver cancer-associated genetic changes persist
A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.
The researchers analyzed liver tissue from 6 noninfected control patients, 18 patients with chronic HCV infection, 21 patients with cured chronic HCV, 4 patients with hepatitis B virus (HBV) infection, and 7 patients with nonalcoholic steatohepatitis (NASH), as well as 8 paired HCC samples with HCV-induced liver disease (Gastroenterology 2019;156:2313–29).
They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.
They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.
“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.
The authors declared that they had no conflicts.
SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.
A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.
The researchers analyzed liver tissue from 6 noninfected control patients, 18 patients with chronic HCV infection, 21 patients with cured chronic HCV, 4 patients with hepatitis B virus (HBV) infection, and 7 patients with nonalcoholic steatohepatitis (NASH), as well as 8 paired HCC samples with HCV-induced liver disease (Gastroenterology 2019;156:2313–29).
They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.
They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.
“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.
The authors declared that they had no conflicts.
SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.
A new study showed that liver tissue from hepatitis C virus (HCV)–infected humans with and without sustained virologic response found epigenetic and gene expression alterations associated with the risk for hepatocellular carcinoma (HCC), according to Nourdine Hamdane, PHD, of the Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.
The researchers analyzed liver tissue from 6 noninfected control patients, 18 patients with chronic HCV infection, 21 patients with cured chronic HCV, 4 patients with hepatitis B virus (HBV) infection, and 7 patients with nonalcoholic steatohepatitis (NASH), as well as 8 paired HCC samples with HCV-induced liver disease (Gastroenterology 2019;156:2313–29).
They found that several altered pathways related to carcinogenesis persisted after cure, including TNF-alpha signaling, inflammatory response, G2M checkpoint, epithelial–mesenchymal transition, and phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin.
They also observed lower levels of H3K27ac mapping to genes related to oxidative phosphorylation pathways, providing evidence supporting a functional role for H3K27ac changes in establishing gene expression patterns that persist after cure and contribute to carcinogenesis, according to the authors.
“Our study exposes a previously undiscovered paradigm showing that chronic HCV infection induces H3K27ac modifications that are associated with HCC risk and that persist after HCV cure,” the authors wrote. “[This study] provides a unique opportunity to uncover novel biomarkers for HCC risk, that is, from plasma through the detection of epigenetic changes of histones bound to circulating DNA complexes. Furthermore, by uncovering virus-induced epigenetic changes as therapeutic targets, our findings offer novel perspectives for HCC prevention – a key unmet medical need,” the researchers concluded.
The authors declared that they had no conflicts.
SOURCE: Hamdane N, et al. 2019; Gastroenterology 156:2313–29.
FROM GASTROENTEROLOGY
Treatment-resistant GERD reported by more than half of patients
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
REPORTING FROM DDW 2019
CMS targets ‘spread pricing’ to help lower drug costs
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
Enzalutamide in castration-sensitive prostate cancer and ctDNA to monitor early colorectal cancer
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
Part 3: Talkin’ ’bout My Generation
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
FDA approves midazolam nasal spray for seizure clusters
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.