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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
How often does risk-reducing salpingo-oophorectomy identify cancer?
Among women with BRCA mutations who underwent risk-reducing bilateral salpingo-oophorectomy, the procedure led to a cancer diagnosis in 3%, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
Of 269 patients, 8 (3%) received a cancer diagnosis. In five cases, the cancer was diagnosed on final pathology, and three had immediate conversion to staging.
The data suggest that gynecologists as well as gynecologic oncologists may perform the procedure, but gynecologists may be less likely to obtain pelvic washings in accordance with guidelines for this indication.
said study author Coralee Toal, MD, of UPMC Magee-Womans Hospital in Pittsburgh. “It is often a diagnosis that is found at the time of pathology, so the initial procedure would not have been changed either way.”
Still, doctors who perform the procedure should follow recommended practices such as obtaining pelvic washings and identifying patients for the procedure within target age ranges, Dr. Toal said.
BRCA1 and BRCA2 mutations confer an increased risk of ovarian and breast cancer, but there is no effective form of ovarian cancer screening. Women with a known mutation may have a bilateral salpingo-oophorectomy to reduce the risk of cancer. The recommended age range for the procedure is 35-40 years for women with BRCA1 mutations and 40-45 years for women with BRCA2 mutations.
When the procedure is performed for this indication, various recommendations apply that may differ from those when the procedure is performed under different circumstances.
During risk-reducing bilateral salpingo-oophorectomy, the surgeon should thoroughly evaluate the abdominal cavity, obtain pelvic washings for cytology, remove at least 2 cm of the infundibulopelvic ligament, and divide the fallopian tube at the uterine cornua.
To assess the incidence of occult ovarian cancer at the time of risk-reducing bilateral salpingo-oophorectomy and surgeon adherence to recommended practices, Dr. Toal and colleagues performed a retrospective chart review.
They included patients who had a known BRCA mutation and underwent a risk-reducing bilateral salpingo-oophorectomy between July 2007 and September 2018. They excluded patients who had a suspicious adnexal mass before the procedure but not a known diagnosis, as well as patients with another malignancy or genetic syndrome.
The researchers evaluated adherence to recommendations by reviewing operative reports.
In all, they reviewed data from 269 patients. In 220 cases, a gynecologic oncologist performed the procedure, and in 49 cases a gynecologist performed the procedure.
Patients tended to be older than would be expected, said Dr. Toal. Patients with BRCA1 mutations had an average age of 46 years, and patients with BRCA2 mutations had an average age of 49 years.
Patients who received a cancer diagnosis were significantly older on average, compared with the other patients: 58 years versus 48 years.
Pelvic washings were performed during 95% of the procedures performed by a gynecologic oncologist, compared with 63% of the procedures performed by a gynecologist. In addition, patients who had the procedure performed by a gynecologist were significantly older than those who had the procedure performed by a gynecologic oncologist (49 vs. 47 years).
Miles Murphy, MD, president of the Society of Gynecologic Surgeons, asked how doctors should weigh the possibility of risk-reducing oophorectomy at the time of benign hysterectomy in patients without a family history of female cancer.
It could be that genetic testing would be appropriate for some of those patients, Dr. Toal said. It is “important to take a thorough family history to make sure that you are identifying anybody who may benefit from genetic counseling and genetic testing, where you might identify an otherwise not known mutation prior to an otherwise benign or routine surgery,” Dr. Toal said. “Then you would have the opportunity to perform this.”
For patients without known mutations, however, “we do know the benefit of ovaries remaining in situ ... including cardiac health,” she said. “You have to remember that people can die of a broken hip as well. The risk of osteoporosis and those things is not zero and in fact may be much higher than their ovarian cancer risk.”
One of the study authors is a surgeon educator for Covidien and Medtronic.
SOURCE: Newcomb LK et al. SGS 2020, Abstract 18.
Among women with BRCA mutations who underwent risk-reducing bilateral salpingo-oophorectomy, the procedure led to a cancer diagnosis in 3%, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
Of 269 patients, 8 (3%) received a cancer diagnosis. In five cases, the cancer was diagnosed on final pathology, and three had immediate conversion to staging.
The data suggest that gynecologists as well as gynecologic oncologists may perform the procedure, but gynecologists may be less likely to obtain pelvic washings in accordance with guidelines for this indication.
said study author Coralee Toal, MD, of UPMC Magee-Womans Hospital in Pittsburgh. “It is often a diagnosis that is found at the time of pathology, so the initial procedure would not have been changed either way.”
Still, doctors who perform the procedure should follow recommended practices such as obtaining pelvic washings and identifying patients for the procedure within target age ranges, Dr. Toal said.
BRCA1 and BRCA2 mutations confer an increased risk of ovarian and breast cancer, but there is no effective form of ovarian cancer screening. Women with a known mutation may have a bilateral salpingo-oophorectomy to reduce the risk of cancer. The recommended age range for the procedure is 35-40 years for women with BRCA1 mutations and 40-45 years for women with BRCA2 mutations.
When the procedure is performed for this indication, various recommendations apply that may differ from those when the procedure is performed under different circumstances.
During risk-reducing bilateral salpingo-oophorectomy, the surgeon should thoroughly evaluate the abdominal cavity, obtain pelvic washings for cytology, remove at least 2 cm of the infundibulopelvic ligament, and divide the fallopian tube at the uterine cornua.
To assess the incidence of occult ovarian cancer at the time of risk-reducing bilateral salpingo-oophorectomy and surgeon adherence to recommended practices, Dr. Toal and colleagues performed a retrospective chart review.
They included patients who had a known BRCA mutation and underwent a risk-reducing bilateral salpingo-oophorectomy between July 2007 and September 2018. They excluded patients who had a suspicious adnexal mass before the procedure but not a known diagnosis, as well as patients with another malignancy or genetic syndrome.
The researchers evaluated adherence to recommendations by reviewing operative reports.
In all, they reviewed data from 269 patients. In 220 cases, a gynecologic oncologist performed the procedure, and in 49 cases a gynecologist performed the procedure.
Patients tended to be older than would be expected, said Dr. Toal. Patients with BRCA1 mutations had an average age of 46 years, and patients with BRCA2 mutations had an average age of 49 years.
Patients who received a cancer diagnosis were significantly older on average, compared with the other patients: 58 years versus 48 years.
Pelvic washings were performed during 95% of the procedures performed by a gynecologic oncologist, compared with 63% of the procedures performed by a gynecologist. In addition, patients who had the procedure performed by a gynecologist were significantly older than those who had the procedure performed by a gynecologic oncologist (49 vs. 47 years).
Miles Murphy, MD, president of the Society of Gynecologic Surgeons, asked how doctors should weigh the possibility of risk-reducing oophorectomy at the time of benign hysterectomy in patients without a family history of female cancer.
It could be that genetic testing would be appropriate for some of those patients, Dr. Toal said. It is “important to take a thorough family history to make sure that you are identifying anybody who may benefit from genetic counseling and genetic testing, where you might identify an otherwise not known mutation prior to an otherwise benign or routine surgery,” Dr. Toal said. “Then you would have the opportunity to perform this.”
For patients without known mutations, however, “we do know the benefit of ovaries remaining in situ ... including cardiac health,” she said. “You have to remember that people can die of a broken hip as well. The risk of osteoporosis and those things is not zero and in fact may be much higher than their ovarian cancer risk.”
One of the study authors is a surgeon educator for Covidien and Medtronic.
SOURCE: Newcomb LK et al. SGS 2020, Abstract 18.
Among women with BRCA mutations who underwent risk-reducing bilateral salpingo-oophorectomy, the procedure led to a cancer diagnosis in 3%, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
Of 269 patients, 8 (3%) received a cancer diagnosis. In five cases, the cancer was diagnosed on final pathology, and three had immediate conversion to staging.
The data suggest that gynecologists as well as gynecologic oncologists may perform the procedure, but gynecologists may be less likely to obtain pelvic washings in accordance with guidelines for this indication.
said study author Coralee Toal, MD, of UPMC Magee-Womans Hospital in Pittsburgh. “It is often a diagnosis that is found at the time of pathology, so the initial procedure would not have been changed either way.”
Still, doctors who perform the procedure should follow recommended practices such as obtaining pelvic washings and identifying patients for the procedure within target age ranges, Dr. Toal said.
BRCA1 and BRCA2 mutations confer an increased risk of ovarian and breast cancer, but there is no effective form of ovarian cancer screening. Women with a known mutation may have a bilateral salpingo-oophorectomy to reduce the risk of cancer. The recommended age range for the procedure is 35-40 years for women with BRCA1 mutations and 40-45 years for women with BRCA2 mutations.
When the procedure is performed for this indication, various recommendations apply that may differ from those when the procedure is performed under different circumstances.
During risk-reducing bilateral salpingo-oophorectomy, the surgeon should thoroughly evaluate the abdominal cavity, obtain pelvic washings for cytology, remove at least 2 cm of the infundibulopelvic ligament, and divide the fallopian tube at the uterine cornua.
To assess the incidence of occult ovarian cancer at the time of risk-reducing bilateral salpingo-oophorectomy and surgeon adherence to recommended practices, Dr. Toal and colleagues performed a retrospective chart review.
They included patients who had a known BRCA mutation and underwent a risk-reducing bilateral salpingo-oophorectomy between July 2007 and September 2018. They excluded patients who had a suspicious adnexal mass before the procedure but not a known diagnosis, as well as patients with another malignancy or genetic syndrome.
The researchers evaluated adherence to recommendations by reviewing operative reports.
In all, they reviewed data from 269 patients. In 220 cases, a gynecologic oncologist performed the procedure, and in 49 cases a gynecologist performed the procedure.
Patients tended to be older than would be expected, said Dr. Toal. Patients with BRCA1 mutations had an average age of 46 years, and patients with BRCA2 mutations had an average age of 49 years.
Patients who received a cancer diagnosis were significantly older on average, compared with the other patients: 58 years versus 48 years.
Pelvic washings were performed during 95% of the procedures performed by a gynecologic oncologist, compared with 63% of the procedures performed by a gynecologist. In addition, patients who had the procedure performed by a gynecologist were significantly older than those who had the procedure performed by a gynecologic oncologist (49 vs. 47 years).
Miles Murphy, MD, president of the Society of Gynecologic Surgeons, asked how doctors should weigh the possibility of risk-reducing oophorectomy at the time of benign hysterectomy in patients without a family history of female cancer.
It could be that genetic testing would be appropriate for some of those patients, Dr. Toal said. It is “important to take a thorough family history to make sure that you are identifying anybody who may benefit from genetic counseling and genetic testing, where you might identify an otherwise not known mutation prior to an otherwise benign or routine surgery,” Dr. Toal said. “Then you would have the opportunity to perform this.”
For patients without known mutations, however, “we do know the benefit of ovaries remaining in situ ... including cardiac health,” she said. “You have to remember that people can die of a broken hip as well. The risk of osteoporosis and those things is not zero and in fact may be much higher than their ovarian cancer risk.”
One of the study authors is a surgeon educator for Covidien and Medtronic.
SOURCE: Newcomb LK et al. SGS 2020, Abstract 18.
FROM SGS 2020
Better continence rate gives robotic prostatectomy the edge
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
FROM EAU20
So, you’ve been sued. What now?
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
FROM SPD 2020
Range of interventions reduces likelihood of infection after hysterectomy
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
FROM SGS 2020
Higher death rate seen in cancer patients with nosocomial COVID-19
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
FROM AACR: COVID-19 AND CANCER
Aerobic exercise may up brain-training benefits in schizophrenia
Recent research has shown that social cognition training can benefit patients with schizophrenia, and a new study suggests that adding regular aerobic exercise sessions substantially increases the improvements in a dose-response manner.
In a randomized controlled trial (RCT) in 47 patients with schizophrenia, improvement in cognition tripled after adding an aerobic exercise program to cognitive training (CT) compared with CT alone.
Investigators, led by Keith H. Nuechterlein, PhD, professor of psychology, University of California, Los Angeles, note that there is “increasing evidence” to support the use of aerobic exercise to improve cognition and functioning in schizophrenia.
However, the “extent to which these gains are dependent on the amount of aerobic exercise completed remains unclear, although variability in adherence to intended exercise regiments is evident,” they write.
They also point out that
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Body Circuit Training
In the study, 47 patients with first-episode schizophrenia were randomly assigned to receive 6 months of CT alone or 6 months of CT plus exercise (CT+E).
All participants underwent 4 hours per week of computerized CT with BrainHQ and SocialVille programs (PositScience).
Patients in the CT+E group also took part in total body circuit training. Two aerobic exercise sessions per week were held at the clinic and two were to be completed at home. The goal was 150 minutes of exercise per week in total.
Exercise intensity was titrated to the individual, at a target of 60% to 80% of heart rate reserve.
Both the CT and CT+E groups showed cognitive gains on the MATRICS Consensus Cognitive Battery (MCCB) test, as well as work/school functioning gains on the Global Assessment Scale: Role.
However, results showed that the improvements in the CT+E group were three times greater than those shown in the CT group (P < .02 for the MCCB overall composite score).
Cognitive Gain Predictors
Because there were also substantial differences in the magnitude of cognitive improvement between the CT+E patients, the investigators sought to identify predictors of cognitive gain.
They found that patients in the CT+E group completed, on average, 85% of their in-clinic exercise sessions but only 39% of their home exercise sessions.
Those who completed a higher overall proportion of the exercise sessions had the largest cognitive gains (P = .03). This relationship was even stronger for patients who completed home exercise sessions (P = .02).
“Thus, aerobic exercise showed a dose-response relationship to cognitive improvement,” the researchers report.
To improve completion rates for home sessions, the investigators tried paying the patients $5 for each session completed, which was “helpful” but did not iron out the variability in adherence.
They also tried assigning points for completing the most exercise sessions in the desired heart rate. They awarded a monthly winner and divided the patients into two completion groups. However, there were “mixed” results.
“Development of systematic incentive strategies to encourage regular aerobic exercise will be critical to successful dissemination of exercise programs as part of the treatment of schizophrenia,” the researchers write.
They add that “pilot work with smartphone reminder systems is underway.”
Effective, but Intensity Is Key
Commenting on the study for Medscape Medical News, David Kimhy, PhD, program leader for New Interventions in Schizophrenia, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said the results are consistent with previous research.
Aerobic exercise is “highly effective in improving neurocognitive functioning” in patients with schizophrenia, said Kimhy, who was not involved in the research.
“Many individuals with schizophrenia tend to have a highly sedentary lifestyle resulting in poor aerobic fitness,” he said. “Thus, aerobic fitness may represent one of the few modifiable risk factors for ameliorating poor neurocognitive functioning.”
He noted that those benefits are in addition to “the many cardiovascular and health benefits aerobic exercise provide, which are nearly nonexistent for cognitive training and pharmacological interventions.”
However, even if patients do take part in exercise sessions, “an important issue is in-session fidelity with training goals, as individuals may attend scheduled sessions but exercise very lightly,” Kimhy noted.
He pointed out that the proportion of time these patients exercise at their designated target training intensity is highly correlated with neurocognitive improvement. Consequently, “exercising with a trainer may increase both attendance and in-session training fidelity.”
Overall, although the current study suggests that in-clinic exercise sessions can be advantageous, “the recent COVID-19 pandemic made such options very challenging,” Kimhy said.
“To address this issue, our research group and others are currently examining employment of aerobic exercise training at home, connected with trainers via live two-way telehealth video calls,” he added.
Plasticity-Based Training
Two recent studies also indicate that remotely administered training programs can improve social cognition.
In the first study, published online July 2 in Schizophrenia Bulletin, 147 outpatients with schizophrenia were randomly assigned to complete 40 sessions of either SocialVille plasticity-based social cognition training or computer-based games such as crossword puzzles and solitaire.
“To develop these social cognition training exercises, we analyzed a tremendous amount of prior research about how the brain processes social information,” lead author Mor Nahum, PhD, School of Occupational Therapy, Hebrew University, Jerusalem, Israel, said in a press release.
“It turns out that social cognition requires fast and accurate brain information processing, so we developed exercises that trained the brain to process social stimuli, like faces and emotions, quickly and accurately,” Nahum added.
The interventions were conducted at home, with 55 participants completing the cognitive training and 53 completing the computer game sessions. (The remaining 39 either dropped out or withdrew.)
An average of 28 hours of social cognition training over 3 months was associated with a significant improvement on social cognitive composite scores compared with computer games (P < .001), but not on the UCSD Performance-Based Skills Assessment.
Further analysis suggested that more time spent on the cognitive training was associated with greater improvements in social cognition and social functioning, as well as on a motivation subscale.
The results “provide support for the efficacy of a remote, plasticity-based social cognitive training program,” the investigators write.
Such programs “may serve as a cost-effective adjunct to existing psychosocial treatments,” they add.
Auditory vs Visual Training
In the other study, published online May 21 in Schizophrenia Research, investigators led by Rogerio Panizzutti, MD, PhD, Instituto de Ciencias Biomedicas, Federal University of Rio de Janeiro, Brazil, randomly assigned 79 patients with schizophrenia to 40 hours of auditory or visual computerized training.
The exercises were dynamically equivalent between the two types of training, and their difficulty increased as the training progressed.
Both groups showed improvements in reasoning, problem-solving, and reported symptoms. However, the group receiving visual training also had greater improvement in global cognition and attention than the group receiving auditory training.
All studies were supported by Posit Science Corporation. The study authors and Kimhy have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Recent research has shown that social cognition training can benefit patients with schizophrenia, and a new study suggests that adding regular aerobic exercise sessions substantially increases the improvements in a dose-response manner.
In a randomized controlled trial (RCT) in 47 patients with schizophrenia, improvement in cognition tripled after adding an aerobic exercise program to cognitive training (CT) compared with CT alone.
Investigators, led by Keith H. Nuechterlein, PhD, professor of psychology, University of California, Los Angeles, note that there is “increasing evidence” to support the use of aerobic exercise to improve cognition and functioning in schizophrenia.
However, the “extent to which these gains are dependent on the amount of aerobic exercise completed remains unclear, although variability in adherence to intended exercise regiments is evident,” they write.
They also point out that
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Body Circuit Training
In the study, 47 patients with first-episode schizophrenia were randomly assigned to receive 6 months of CT alone or 6 months of CT plus exercise (CT+E).
All participants underwent 4 hours per week of computerized CT with BrainHQ and SocialVille programs (PositScience).
Patients in the CT+E group also took part in total body circuit training. Two aerobic exercise sessions per week were held at the clinic and two were to be completed at home. The goal was 150 minutes of exercise per week in total.
Exercise intensity was titrated to the individual, at a target of 60% to 80% of heart rate reserve.
Both the CT and CT+E groups showed cognitive gains on the MATRICS Consensus Cognitive Battery (MCCB) test, as well as work/school functioning gains on the Global Assessment Scale: Role.
However, results showed that the improvements in the CT+E group were three times greater than those shown in the CT group (P < .02 for the MCCB overall composite score).
Cognitive Gain Predictors
Because there were also substantial differences in the magnitude of cognitive improvement between the CT+E patients, the investigators sought to identify predictors of cognitive gain.
They found that patients in the CT+E group completed, on average, 85% of their in-clinic exercise sessions but only 39% of their home exercise sessions.
Those who completed a higher overall proportion of the exercise sessions had the largest cognitive gains (P = .03). This relationship was even stronger for patients who completed home exercise sessions (P = .02).
“Thus, aerobic exercise showed a dose-response relationship to cognitive improvement,” the researchers report.
To improve completion rates for home sessions, the investigators tried paying the patients $5 for each session completed, which was “helpful” but did not iron out the variability in adherence.
They also tried assigning points for completing the most exercise sessions in the desired heart rate. They awarded a monthly winner and divided the patients into two completion groups. However, there were “mixed” results.
“Development of systematic incentive strategies to encourage regular aerobic exercise will be critical to successful dissemination of exercise programs as part of the treatment of schizophrenia,” the researchers write.
They add that “pilot work with smartphone reminder systems is underway.”
Effective, but Intensity Is Key
Commenting on the study for Medscape Medical News, David Kimhy, PhD, program leader for New Interventions in Schizophrenia, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said the results are consistent with previous research.
Aerobic exercise is “highly effective in improving neurocognitive functioning” in patients with schizophrenia, said Kimhy, who was not involved in the research.
“Many individuals with schizophrenia tend to have a highly sedentary lifestyle resulting in poor aerobic fitness,” he said. “Thus, aerobic fitness may represent one of the few modifiable risk factors for ameliorating poor neurocognitive functioning.”
He noted that those benefits are in addition to “the many cardiovascular and health benefits aerobic exercise provide, which are nearly nonexistent for cognitive training and pharmacological interventions.”
However, even if patients do take part in exercise sessions, “an important issue is in-session fidelity with training goals, as individuals may attend scheduled sessions but exercise very lightly,” Kimhy noted.
He pointed out that the proportion of time these patients exercise at their designated target training intensity is highly correlated with neurocognitive improvement. Consequently, “exercising with a trainer may increase both attendance and in-session training fidelity.”
Overall, although the current study suggests that in-clinic exercise sessions can be advantageous, “the recent COVID-19 pandemic made such options very challenging,” Kimhy said.
“To address this issue, our research group and others are currently examining employment of aerobic exercise training at home, connected with trainers via live two-way telehealth video calls,” he added.
Plasticity-Based Training
Two recent studies also indicate that remotely administered training programs can improve social cognition.
In the first study, published online July 2 in Schizophrenia Bulletin, 147 outpatients with schizophrenia were randomly assigned to complete 40 sessions of either SocialVille plasticity-based social cognition training or computer-based games such as crossword puzzles and solitaire.
“To develop these social cognition training exercises, we analyzed a tremendous amount of prior research about how the brain processes social information,” lead author Mor Nahum, PhD, School of Occupational Therapy, Hebrew University, Jerusalem, Israel, said in a press release.
“It turns out that social cognition requires fast and accurate brain information processing, so we developed exercises that trained the brain to process social stimuli, like faces and emotions, quickly and accurately,” Nahum added.
The interventions were conducted at home, with 55 participants completing the cognitive training and 53 completing the computer game sessions. (The remaining 39 either dropped out or withdrew.)
An average of 28 hours of social cognition training over 3 months was associated with a significant improvement on social cognitive composite scores compared with computer games (P < .001), but not on the UCSD Performance-Based Skills Assessment.
Further analysis suggested that more time spent on the cognitive training was associated with greater improvements in social cognition and social functioning, as well as on a motivation subscale.
The results “provide support for the efficacy of a remote, plasticity-based social cognitive training program,” the investigators write.
Such programs “may serve as a cost-effective adjunct to existing psychosocial treatments,” they add.
Auditory vs Visual Training
In the other study, published online May 21 in Schizophrenia Research, investigators led by Rogerio Panizzutti, MD, PhD, Instituto de Ciencias Biomedicas, Federal University of Rio de Janeiro, Brazil, randomly assigned 79 patients with schizophrenia to 40 hours of auditory or visual computerized training.
The exercises were dynamically equivalent between the two types of training, and their difficulty increased as the training progressed.
Both groups showed improvements in reasoning, problem-solving, and reported symptoms. However, the group receiving visual training also had greater improvement in global cognition and attention than the group receiving auditory training.
All studies were supported by Posit Science Corporation. The study authors and Kimhy have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Recent research has shown that social cognition training can benefit patients with schizophrenia, and a new study suggests that adding regular aerobic exercise sessions substantially increases the improvements in a dose-response manner.
In a randomized controlled trial (RCT) in 47 patients with schizophrenia, improvement in cognition tripled after adding an aerobic exercise program to cognitive training (CT) compared with CT alone.
Investigators, led by Keith H. Nuechterlein, PhD, professor of psychology, University of California, Los Angeles, note that there is “increasing evidence” to support the use of aerobic exercise to improve cognition and functioning in schizophrenia.
However, the “extent to which these gains are dependent on the amount of aerobic exercise completed remains unclear, although variability in adherence to intended exercise regiments is evident,” they write.
They also point out that
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Body Circuit Training
In the study, 47 patients with first-episode schizophrenia were randomly assigned to receive 6 months of CT alone or 6 months of CT plus exercise (CT+E).
All participants underwent 4 hours per week of computerized CT with BrainHQ and SocialVille programs (PositScience).
Patients in the CT+E group also took part in total body circuit training. Two aerobic exercise sessions per week were held at the clinic and two were to be completed at home. The goal was 150 minutes of exercise per week in total.
Exercise intensity was titrated to the individual, at a target of 60% to 80% of heart rate reserve.
Both the CT and CT+E groups showed cognitive gains on the MATRICS Consensus Cognitive Battery (MCCB) test, as well as work/school functioning gains on the Global Assessment Scale: Role.
However, results showed that the improvements in the CT+E group were three times greater than those shown in the CT group (P < .02 for the MCCB overall composite score).
Cognitive Gain Predictors
Because there were also substantial differences in the magnitude of cognitive improvement between the CT+E patients, the investigators sought to identify predictors of cognitive gain.
They found that patients in the CT+E group completed, on average, 85% of their in-clinic exercise sessions but only 39% of their home exercise sessions.
Those who completed a higher overall proportion of the exercise sessions had the largest cognitive gains (P = .03). This relationship was even stronger for patients who completed home exercise sessions (P = .02).
“Thus, aerobic exercise showed a dose-response relationship to cognitive improvement,” the researchers report.
To improve completion rates for home sessions, the investigators tried paying the patients $5 for each session completed, which was “helpful” but did not iron out the variability in adherence.
They also tried assigning points for completing the most exercise sessions in the desired heart rate. They awarded a monthly winner and divided the patients into two completion groups. However, there were “mixed” results.
“Development of systematic incentive strategies to encourage regular aerobic exercise will be critical to successful dissemination of exercise programs as part of the treatment of schizophrenia,” the researchers write.
They add that “pilot work with smartphone reminder systems is underway.”
Effective, but Intensity Is Key
Commenting on the study for Medscape Medical News, David Kimhy, PhD, program leader for New Interventions in Schizophrenia, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said the results are consistent with previous research.
Aerobic exercise is “highly effective in improving neurocognitive functioning” in patients with schizophrenia, said Kimhy, who was not involved in the research.
“Many individuals with schizophrenia tend to have a highly sedentary lifestyle resulting in poor aerobic fitness,” he said. “Thus, aerobic fitness may represent one of the few modifiable risk factors for ameliorating poor neurocognitive functioning.”
He noted that those benefits are in addition to “the many cardiovascular and health benefits aerobic exercise provide, which are nearly nonexistent for cognitive training and pharmacological interventions.”
However, even if patients do take part in exercise sessions, “an important issue is in-session fidelity with training goals, as individuals may attend scheduled sessions but exercise very lightly,” Kimhy noted.
He pointed out that the proportion of time these patients exercise at their designated target training intensity is highly correlated with neurocognitive improvement. Consequently, “exercising with a trainer may increase both attendance and in-session training fidelity.”
Overall, although the current study suggests that in-clinic exercise sessions can be advantageous, “the recent COVID-19 pandemic made such options very challenging,” Kimhy said.
“To address this issue, our research group and others are currently examining employment of aerobic exercise training at home, connected with trainers via live two-way telehealth video calls,” he added.
Plasticity-Based Training
Two recent studies also indicate that remotely administered training programs can improve social cognition.
In the first study, published online July 2 in Schizophrenia Bulletin, 147 outpatients with schizophrenia were randomly assigned to complete 40 sessions of either SocialVille plasticity-based social cognition training or computer-based games such as crossword puzzles and solitaire.
“To develop these social cognition training exercises, we analyzed a tremendous amount of prior research about how the brain processes social information,” lead author Mor Nahum, PhD, School of Occupational Therapy, Hebrew University, Jerusalem, Israel, said in a press release.
“It turns out that social cognition requires fast and accurate brain information processing, so we developed exercises that trained the brain to process social stimuli, like faces and emotions, quickly and accurately,” Nahum added.
The interventions were conducted at home, with 55 participants completing the cognitive training and 53 completing the computer game sessions. (The remaining 39 either dropped out or withdrew.)
An average of 28 hours of social cognition training over 3 months was associated with a significant improvement on social cognitive composite scores compared with computer games (P < .001), but not on the UCSD Performance-Based Skills Assessment.
Further analysis suggested that more time spent on the cognitive training was associated with greater improvements in social cognition and social functioning, as well as on a motivation subscale.
The results “provide support for the efficacy of a remote, plasticity-based social cognitive training program,” the investigators write.
Such programs “may serve as a cost-effective adjunct to existing psychosocial treatments,” they add.
Auditory vs Visual Training
In the other study, published online May 21 in Schizophrenia Research, investigators led by Rogerio Panizzutti, MD, PhD, Instituto de Ciencias Biomedicas, Federal University of Rio de Janeiro, Brazil, randomly assigned 79 patients with schizophrenia to 40 hours of auditory or visual computerized training.
The exercises were dynamically equivalent between the two types of training, and their difficulty increased as the training progressed.
Both groups showed improvements in reasoning, problem-solving, and reported symptoms. However, the group receiving visual training also had greater improvement in global cognition and attention than the group receiving auditory training.
All studies were supported by Posit Science Corporation. The study authors and Kimhy have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Memphis clinic created to care for children and adolescents diagnosed with melanoma
Pediatric melanoma remains a rare diagnosis – representing just 1%-4% of all melanomas – and it continues to be poorly understood.
“There are many questions about its biology, histopathology, and clinical behavior,” Teresa S. Wright, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “This diagnosis can be very difficult to establish. These lesions can be very unusual and require several different expert opinions to arrive at a diagnosis. Oftentimes, there may be an initial misdiagnosis or disagreement about diagnosis. This frequently results in a delay of treatment.”
Dr. Wright, chief of pediatric dermatology at LeBonheur Children’s Hospital and associate professor of dermatology at the University of Tennessee Health Science Center, Memphis, added that once a diagnosis of pediatric melanoma has been established, things don’t get any easier because of the lack of evidence-based guidelines for management. “There are really no standard recommendations regarding the workup, treatment, or follow-up for these patients,” she said.
Referral Clinic Launched
In 2016, under the direction of Alberto Pappo, MD, director of the solid tumor division at St. Jude Children’s Research Hospital in Memphis, Dr. Wright and several colleagues at “As a group, we address questions surrounding the diagnosis and pathology of the patient’s lesion, as well as therapy and follow-up for each individual patient,” Dr. Wright said.
Members of the clinic team include a pediatric oncologist, an adult oncologist, and a surgical oncologist (all with melanoma expertise); a pediatric surgeon, a pediatric dermatologist, a pediatric radiologist, a pathologist, and a nursing team, which includes a pediatric nurse practitioner, three registered nurses, and other support staff, including those that provide genetic counseling and child life specialists. To be eligible for the clinic, which typically is scheduled in April and November every year, patients must be no older than 21 years, must be referred by a physician, and must have a diagnosis of melanoma or Spitzoid melanoma, not including ocular melanoma. They must be currently undergoing treatment or followed by a physician who requests or supports a consult to optimize clinical management of the patient. St. Jude foots the bill for all travel, housing, and meal expenses. All pertinent materials are collected in advance of the 2-day clinic, including medical records, lab results, histology slides, tissue samples, and radiographic studies. The pathologist performs an initial review of the histology slides and additional genomic studies are performed based on the pathologist’s diagnosis.
Patients typically arrive on a Wednesday evening and have their first clinic visit Thursday morning. First, the oncology team performs a thorough history and physical examination, then Dr. Wright performs a thorough skin examination and a professional photographer captures images of relevant skin lesions. That afternoon, members of the multidisciplinary team meet to review each patient’s entire course, including previous surgeries and any medical therapies.
“We review their pathology, including histology slides and results of any genomic studies,” Dr. Wright said. “We also review all the radiographic studies they’ve had, which may include plain films, CT scans, PET scans, MRIs, and ultrasounds. Then we form a consensus opinion regarding a diagnosis. Sometimes we feel a change in diagnosis is warranted.” For example, she added, “we have had a number of patients referred to us with an initial diagnosis of Spitzoid melanoma where, after review, we felt that a diagnosis of atypical Spitzoid tumor was more appropriate for them. We also talk about any treatment they’ve had in the past and decide if any additional surgical or medical treatment is indicated at this time. Lastly, we make recommendations for follow-up or surveillance.”
On Thursday evening, the clinic sponsors a casual dinner for families, which features an educational presentation by one or more faculty members. Topics covered in the past include sun protection, melanoma in children, and an overview of melanoma research.
The next morning, each family meets with the panel of specialists. “The team members introduce themselves and describe their roles within the team, and family members introduce themselves and tell their child’s story. “Then, each team member describes their findings and gives their overall assessment. The family receives recommendations for any additional testing, therapy, and follow-up, and the patient and family’s questions are answered.”
Families are also offered the opportunity to participate in research. “They can donate samples to a tissue bank, and patients may qualify for future clinical trials at St. Jude Children’s Research Hospital,” Dr. Wright said.
To date, 20 female and 18 male patients have traveled to the Pediatric and Adolescent Melanoma Referral Clinic from 21 states and Puerto Rico for assessment and consultation. They ranged in age from 6 months to 18 years, and their average age is 9 years. Members of the clinic team have seen 13 patients with a diagnosis of Spitzoid melanoma, 10 with malignant melanoma, 8 with atypical melanocytic neoplasm, 3 with congenital melanoma, 3 with atypical Spitz tumor, and 1 with congenital melanocytic nevus.
The median age at diagnosis was 12 years for malignant melanoma and 9 years for Spitzoid melanoma; and the male to female ratio is 7:3 for malignant melanoma and 4:9 for Spitzoid melanoma. These are the patients who have come to the multidisciplinary clinic, these specialists see other patients with a diagnosis of pediatric or adolescent melanoma at other times of the year, Dr. Wright noted.
A common refrain she hears from pediatric melanoma patients and their families is that the initial skin lesion appears to be unremarkable. “Many times, this is a skin-colored or pink papule, which starts out looking very much like a molluscum or a wart or an insect bite, or something else that nobody’s worried about,” Dr. Wright said. “But over time, something happens, and the common factor is rapid growth. Time and again when I ask parents, ‘What changed? What got your attention?’ The answer is nearly always rapid growth.”
She emphasized that patients frequently arrive at the clinic with multiple opinions about their diagnosis. “It’s not unusual for a significant amount of time to pass between the initial biopsy and the final diagnosis,” she said. “Given the lack of evidence-based guidelines for children, a delay in diagnosis can make decisions about management even more difficult. Because pediatric melanoma is so rare, and there are no standard guidelines for management, there’s a major lack of consistency in terms of how patients are evaluated, treated, and followed.”
Dr. Wright said the team’s goals are to continue the biannual clinic and collect more data and tissue samples for further genomic studies on pediatric melanoma. “Ultimately, we would like to hold a consensus summit meeting of experts to develop and publish evidence-based guidelines for the management of pediatric and adolescent melanoma.”
Dr. Wright reported having no relevant disclosures.
Pediatric melanoma remains a rare diagnosis – representing just 1%-4% of all melanomas – and it continues to be poorly understood.
“There are many questions about its biology, histopathology, and clinical behavior,” Teresa S. Wright, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “This diagnosis can be very difficult to establish. These lesions can be very unusual and require several different expert opinions to arrive at a diagnosis. Oftentimes, there may be an initial misdiagnosis or disagreement about diagnosis. This frequently results in a delay of treatment.”
Dr. Wright, chief of pediatric dermatology at LeBonheur Children’s Hospital and associate professor of dermatology at the University of Tennessee Health Science Center, Memphis, added that once a diagnosis of pediatric melanoma has been established, things don’t get any easier because of the lack of evidence-based guidelines for management. “There are really no standard recommendations regarding the workup, treatment, or follow-up for these patients,” she said.
Referral Clinic Launched
In 2016, under the direction of Alberto Pappo, MD, director of the solid tumor division at St. Jude Children’s Research Hospital in Memphis, Dr. Wright and several colleagues at “As a group, we address questions surrounding the diagnosis and pathology of the patient’s lesion, as well as therapy and follow-up for each individual patient,” Dr. Wright said.
Members of the clinic team include a pediatric oncologist, an adult oncologist, and a surgical oncologist (all with melanoma expertise); a pediatric surgeon, a pediatric dermatologist, a pediatric radiologist, a pathologist, and a nursing team, which includes a pediatric nurse practitioner, three registered nurses, and other support staff, including those that provide genetic counseling and child life specialists. To be eligible for the clinic, which typically is scheduled in April and November every year, patients must be no older than 21 years, must be referred by a physician, and must have a diagnosis of melanoma or Spitzoid melanoma, not including ocular melanoma. They must be currently undergoing treatment or followed by a physician who requests or supports a consult to optimize clinical management of the patient. St. Jude foots the bill for all travel, housing, and meal expenses. All pertinent materials are collected in advance of the 2-day clinic, including medical records, lab results, histology slides, tissue samples, and radiographic studies. The pathologist performs an initial review of the histology slides and additional genomic studies are performed based on the pathologist’s diagnosis.
Patients typically arrive on a Wednesday evening and have their first clinic visit Thursday morning. First, the oncology team performs a thorough history and physical examination, then Dr. Wright performs a thorough skin examination and a professional photographer captures images of relevant skin lesions. That afternoon, members of the multidisciplinary team meet to review each patient’s entire course, including previous surgeries and any medical therapies.
“We review their pathology, including histology slides and results of any genomic studies,” Dr. Wright said. “We also review all the radiographic studies they’ve had, which may include plain films, CT scans, PET scans, MRIs, and ultrasounds. Then we form a consensus opinion regarding a diagnosis. Sometimes we feel a change in diagnosis is warranted.” For example, she added, “we have had a number of patients referred to us with an initial diagnosis of Spitzoid melanoma where, after review, we felt that a diagnosis of atypical Spitzoid tumor was more appropriate for them. We also talk about any treatment they’ve had in the past and decide if any additional surgical or medical treatment is indicated at this time. Lastly, we make recommendations for follow-up or surveillance.”
On Thursday evening, the clinic sponsors a casual dinner for families, which features an educational presentation by one or more faculty members. Topics covered in the past include sun protection, melanoma in children, and an overview of melanoma research.
The next morning, each family meets with the panel of specialists. “The team members introduce themselves and describe their roles within the team, and family members introduce themselves and tell their child’s story. “Then, each team member describes their findings and gives their overall assessment. The family receives recommendations for any additional testing, therapy, and follow-up, and the patient and family’s questions are answered.”
Families are also offered the opportunity to participate in research. “They can donate samples to a tissue bank, and patients may qualify for future clinical trials at St. Jude Children’s Research Hospital,” Dr. Wright said.
To date, 20 female and 18 male patients have traveled to the Pediatric and Adolescent Melanoma Referral Clinic from 21 states and Puerto Rico for assessment and consultation. They ranged in age from 6 months to 18 years, and their average age is 9 years. Members of the clinic team have seen 13 patients with a diagnosis of Spitzoid melanoma, 10 with malignant melanoma, 8 with atypical melanocytic neoplasm, 3 with congenital melanoma, 3 with atypical Spitz tumor, and 1 with congenital melanocytic nevus.
The median age at diagnosis was 12 years for malignant melanoma and 9 years for Spitzoid melanoma; and the male to female ratio is 7:3 for malignant melanoma and 4:9 for Spitzoid melanoma. These are the patients who have come to the multidisciplinary clinic, these specialists see other patients with a diagnosis of pediatric or adolescent melanoma at other times of the year, Dr. Wright noted.
A common refrain she hears from pediatric melanoma patients and their families is that the initial skin lesion appears to be unremarkable. “Many times, this is a skin-colored or pink papule, which starts out looking very much like a molluscum or a wart or an insect bite, or something else that nobody’s worried about,” Dr. Wright said. “But over time, something happens, and the common factor is rapid growth. Time and again when I ask parents, ‘What changed? What got your attention?’ The answer is nearly always rapid growth.”
She emphasized that patients frequently arrive at the clinic with multiple opinions about their diagnosis. “It’s not unusual for a significant amount of time to pass between the initial biopsy and the final diagnosis,” she said. “Given the lack of evidence-based guidelines for children, a delay in diagnosis can make decisions about management even more difficult. Because pediatric melanoma is so rare, and there are no standard guidelines for management, there’s a major lack of consistency in terms of how patients are evaluated, treated, and followed.”
Dr. Wright said the team’s goals are to continue the biannual clinic and collect more data and tissue samples for further genomic studies on pediatric melanoma. “Ultimately, we would like to hold a consensus summit meeting of experts to develop and publish evidence-based guidelines for the management of pediatric and adolescent melanoma.”
Dr. Wright reported having no relevant disclosures.
Pediatric melanoma remains a rare diagnosis – representing just 1%-4% of all melanomas – and it continues to be poorly understood.
“There are many questions about its biology, histopathology, and clinical behavior,” Teresa S. Wright, MD, said during the virtual annual meeting of the Society for Pediatric Dermatology. “This diagnosis can be very difficult to establish. These lesions can be very unusual and require several different expert opinions to arrive at a diagnosis. Oftentimes, there may be an initial misdiagnosis or disagreement about diagnosis. This frequently results in a delay of treatment.”
Dr. Wright, chief of pediatric dermatology at LeBonheur Children’s Hospital and associate professor of dermatology at the University of Tennessee Health Science Center, Memphis, added that once a diagnosis of pediatric melanoma has been established, things don’t get any easier because of the lack of evidence-based guidelines for management. “There are really no standard recommendations regarding the workup, treatment, or follow-up for these patients,” she said.
Referral Clinic Launched
In 2016, under the direction of Alberto Pappo, MD, director of the solid tumor division at St. Jude Children’s Research Hospital in Memphis, Dr. Wright and several colleagues at “As a group, we address questions surrounding the diagnosis and pathology of the patient’s lesion, as well as therapy and follow-up for each individual patient,” Dr. Wright said.
Members of the clinic team include a pediatric oncologist, an adult oncologist, and a surgical oncologist (all with melanoma expertise); a pediatric surgeon, a pediatric dermatologist, a pediatric radiologist, a pathologist, and a nursing team, which includes a pediatric nurse practitioner, three registered nurses, and other support staff, including those that provide genetic counseling and child life specialists. To be eligible for the clinic, which typically is scheduled in April and November every year, patients must be no older than 21 years, must be referred by a physician, and must have a diagnosis of melanoma or Spitzoid melanoma, not including ocular melanoma. They must be currently undergoing treatment or followed by a physician who requests or supports a consult to optimize clinical management of the patient. St. Jude foots the bill for all travel, housing, and meal expenses. All pertinent materials are collected in advance of the 2-day clinic, including medical records, lab results, histology slides, tissue samples, and radiographic studies. The pathologist performs an initial review of the histology slides and additional genomic studies are performed based on the pathologist’s diagnosis.
Patients typically arrive on a Wednesday evening and have their first clinic visit Thursday morning. First, the oncology team performs a thorough history and physical examination, then Dr. Wright performs a thorough skin examination and a professional photographer captures images of relevant skin lesions. That afternoon, members of the multidisciplinary team meet to review each patient’s entire course, including previous surgeries and any medical therapies.
“We review their pathology, including histology slides and results of any genomic studies,” Dr. Wright said. “We also review all the radiographic studies they’ve had, which may include plain films, CT scans, PET scans, MRIs, and ultrasounds. Then we form a consensus opinion regarding a diagnosis. Sometimes we feel a change in diagnosis is warranted.” For example, she added, “we have had a number of patients referred to us with an initial diagnosis of Spitzoid melanoma where, after review, we felt that a diagnosis of atypical Spitzoid tumor was more appropriate for them. We also talk about any treatment they’ve had in the past and decide if any additional surgical or medical treatment is indicated at this time. Lastly, we make recommendations for follow-up or surveillance.”
On Thursday evening, the clinic sponsors a casual dinner for families, which features an educational presentation by one or more faculty members. Topics covered in the past include sun protection, melanoma in children, and an overview of melanoma research.
The next morning, each family meets with the panel of specialists. “The team members introduce themselves and describe their roles within the team, and family members introduce themselves and tell their child’s story. “Then, each team member describes their findings and gives their overall assessment. The family receives recommendations for any additional testing, therapy, and follow-up, and the patient and family’s questions are answered.”
Families are also offered the opportunity to participate in research. “They can donate samples to a tissue bank, and patients may qualify for future clinical trials at St. Jude Children’s Research Hospital,” Dr. Wright said.
To date, 20 female and 18 male patients have traveled to the Pediatric and Adolescent Melanoma Referral Clinic from 21 states and Puerto Rico for assessment and consultation. They ranged in age from 6 months to 18 years, and their average age is 9 years. Members of the clinic team have seen 13 patients with a diagnosis of Spitzoid melanoma, 10 with malignant melanoma, 8 with atypical melanocytic neoplasm, 3 with congenital melanoma, 3 with atypical Spitz tumor, and 1 with congenital melanocytic nevus.
The median age at diagnosis was 12 years for malignant melanoma and 9 years for Spitzoid melanoma; and the male to female ratio is 7:3 for malignant melanoma and 4:9 for Spitzoid melanoma. These are the patients who have come to the multidisciplinary clinic, these specialists see other patients with a diagnosis of pediatric or adolescent melanoma at other times of the year, Dr. Wright noted.
A common refrain she hears from pediatric melanoma patients and their families is that the initial skin lesion appears to be unremarkable. “Many times, this is a skin-colored or pink papule, which starts out looking very much like a molluscum or a wart or an insect bite, or something else that nobody’s worried about,” Dr. Wright said. “But over time, something happens, and the common factor is rapid growth. Time and again when I ask parents, ‘What changed? What got your attention?’ The answer is nearly always rapid growth.”
She emphasized that patients frequently arrive at the clinic with multiple opinions about their diagnosis. “It’s not unusual for a significant amount of time to pass between the initial biopsy and the final diagnosis,” she said. “Given the lack of evidence-based guidelines for children, a delay in diagnosis can make decisions about management even more difficult. Because pediatric melanoma is so rare, and there are no standard guidelines for management, there’s a major lack of consistency in terms of how patients are evaluated, treated, and followed.”
Dr. Wright said the team’s goals are to continue the biannual clinic and collect more data and tissue samples for further genomic studies on pediatric melanoma. “Ultimately, we would like to hold a consensus summit meeting of experts to develop and publish evidence-based guidelines for the management of pediatric and adolescent melanoma.”
Dr. Wright reported having no relevant disclosures.
FROM SPD 2020
Parental refusal of neonatal therapy a growing problem
according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.
“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.
Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.
“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.
Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.
Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.
“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”
Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.
Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.
“We do know confidently that oral vitamin K does often result in poor adherence,” she said,
In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.
“One reason that many parents refuse the hepatitis B vaccine is that they do not think their child is at risk,” explained Kimberly Horstman, MD, from Stanford University and John Muir Medical Center in Walnut Creek, Calif.
Yet hepatitis B virus (HBV) infection, which is asymptomatic, can be acquired from many sources, including nonfamily contacts, according to Dr. Horstman.
“The AAP supports universal hepatitis B vaccine within 24 hours of birth for all infants over 2,000 g at birth,” Dr. Horstman said. In those weighing less, the vaccine is recommended within the first month of life.
The risk of parental refusal for recommended neonatal preventive medicines is higher among those with more education and higher income relative to those with less, Dr. Nguyen said. Other predictors include older maternal age, private insurance, and delivery by a midwife or at a birthing center.
Many parents who refuse preventive neonatal medications do not fully grasp what risks they are accepting by avoiding a recommended medication, according to both Dr. Nguyen and Dr. Horstman. In some cases, the goal is to protect their child from the pain of a needlestick, even when the health consequences might include far more invasive and painful therapies if the child develops the disease the medication would have prevented.
In the case of intramuscular vitamin K, “we encourage a presumptive approach,” Dr. Nguyen said. Concerns can then be addressed only if the parents refuse.
For another strategy, Dr. Nguyen recommended counseling parents about the need and value of preventive therapies during pregnancy. She cited data suggesting that it is more difficult to change the minds of parents after delivery.
Echoing this approach in regard to HBV vaccine, Dr. Horstman suggested encouraging colleagues, including obstetricians and community pediatricians, to raise and address this topic during prenatal counseling. By preparing parents for the recommended medications in the prenatal period, concerns can be addressed in advance.
The health risks posed by parents who refuse recommended medications is recognized by the Centers for Disease Control and Prevention. Both Dr. Horstman and Dr. Nguyen said there are handouts from the CDC and the AAP to inform parents of the purpose and benefit of recommended preventive therapies, as well as to equip caregivers with facts for effective counseling.
according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.
“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.
Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.
“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.
Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.
Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.
“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”
Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.
Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.
“We do know confidently that oral vitamin K does often result in poor adherence,” she said,
In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.
“One reason that many parents refuse the hepatitis B vaccine is that they do not think their child is at risk,” explained Kimberly Horstman, MD, from Stanford University and John Muir Medical Center in Walnut Creek, Calif.
Yet hepatitis B virus (HBV) infection, which is asymptomatic, can be acquired from many sources, including nonfamily contacts, according to Dr. Horstman.
“The AAP supports universal hepatitis B vaccine within 24 hours of birth for all infants over 2,000 g at birth,” Dr. Horstman said. In those weighing less, the vaccine is recommended within the first month of life.
The risk of parental refusal for recommended neonatal preventive medicines is higher among those with more education and higher income relative to those with less, Dr. Nguyen said. Other predictors include older maternal age, private insurance, and delivery by a midwife or at a birthing center.
Many parents who refuse preventive neonatal medications do not fully grasp what risks they are accepting by avoiding a recommended medication, according to both Dr. Nguyen and Dr. Horstman. In some cases, the goal is to protect their child from the pain of a needlestick, even when the health consequences might include far more invasive and painful therapies if the child develops the disease the medication would have prevented.
In the case of intramuscular vitamin K, “we encourage a presumptive approach,” Dr. Nguyen said. Concerns can then be addressed only if the parents refuse.
For another strategy, Dr. Nguyen recommended counseling parents about the need and value of preventive therapies during pregnancy. She cited data suggesting that it is more difficult to change the minds of parents after delivery.
Echoing this approach in regard to HBV vaccine, Dr. Horstman suggested encouraging colleagues, including obstetricians and community pediatricians, to raise and address this topic during prenatal counseling. By preparing parents for the recommended medications in the prenatal period, concerns can be addressed in advance.
The health risks posed by parents who refuse recommended medications is recognized by the Centers for Disease Control and Prevention. Both Dr. Horstman and Dr. Nguyen said there are handouts from the CDC and the AAP to inform parents of the purpose and benefit of recommended preventive therapies, as well as to equip caregivers with facts for effective counseling.
according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.
“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.
Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.
“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.
Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.
Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.
“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”
Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.
Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.
“We do know confidently that oral vitamin K does often result in poor adherence,” she said,
In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.
“One reason that many parents refuse the hepatitis B vaccine is that they do not think their child is at risk,” explained Kimberly Horstman, MD, from Stanford University and John Muir Medical Center in Walnut Creek, Calif.
Yet hepatitis B virus (HBV) infection, which is asymptomatic, can be acquired from many sources, including nonfamily contacts, according to Dr. Horstman.
“The AAP supports universal hepatitis B vaccine within 24 hours of birth for all infants over 2,000 g at birth,” Dr. Horstman said. In those weighing less, the vaccine is recommended within the first month of life.
The risk of parental refusal for recommended neonatal preventive medicines is higher among those with more education and higher income relative to those with less, Dr. Nguyen said. Other predictors include older maternal age, private insurance, and delivery by a midwife or at a birthing center.
Many parents who refuse preventive neonatal medications do not fully grasp what risks they are accepting by avoiding a recommended medication, according to both Dr. Nguyen and Dr. Horstman. In some cases, the goal is to protect their child from the pain of a needlestick, even when the health consequences might include far more invasive and painful therapies if the child develops the disease the medication would have prevented.
In the case of intramuscular vitamin K, “we encourage a presumptive approach,” Dr. Nguyen said. Concerns can then be addressed only if the parents refuse.
For another strategy, Dr. Nguyen recommended counseling parents about the need and value of preventive therapies during pregnancy. She cited data suggesting that it is more difficult to change the minds of parents after delivery.
Echoing this approach in regard to HBV vaccine, Dr. Horstman suggested encouraging colleagues, including obstetricians and community pediatricians, to raise and address this topic during prenatal counseling. By preparing parents for the recommended medications in the prenatal period, concerns can be addressed in advance.
The health risks posed by parents who refuse recommended medications is recognized by the Centers for Disease Control and Prevention. Both Dr. Horstman and Dr. Nguyen said there are handouts from the CDC and the AAP to inform parents of the purpose and benefit of recommended preventive therapies, as well as to equip caregivers with facts for effective counseling.
FROM PHM 2020
Large cohort study: Bevacizumab safe, effective for severe HHT bleeds
Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.
In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.
As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.
Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.
Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.
Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.
The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted
Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.
Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.
Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.
HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.
“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.
Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.
“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”
However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.
In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.
To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.
Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.
“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.
Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”
As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.
“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.
Dr. Al-Samkari agreed that the possibility is worth exploring.
“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.
“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”
Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.
SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.
Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.
In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.
As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.
Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.
Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.
Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.
The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted
Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.
Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.
Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.
HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.
“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.
Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.
“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”
However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.
In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.
To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.
Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.
“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.
Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”
As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.
“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.
Dr. Al-Samkari agreed that the possibility is worth exploring.
“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.
“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”
Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.
SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.
Systemic bevacizumab is safe and highly effective for the management of chronic bleeding and anemia in patients with hereditary hemorrhagic telangiectasia (HHT), according to findings from an international observational study.
In 238 patients from 12 international centers who were treated with bevacizumab for a median of 12 months, mean hemoglobin levels increased by 3.2 g/dL (mean pre- and posttreatment levels, 8.6 vs. 11.8 g/dL), and epistaxis severity scores (ESS) decreased by a mean of 3.4 points (pre- and posttreatment scores, 6.8 vs. 3.4 points), Hanny Al-Samkari, MD, reported at the International Society on Thrombosis and Haemostasis virtual congress.
As established in prior studies, the minimal clinically important difference in the ESS, a well-validated 10-point bleeding score in HHT, is 0.71 points; the mean reduction seen in this study was 4.75 times that, noted Dr. Al-Samkari, a clinical investigator and hematologist at Massachusetts General Hospital, Boston.
Further, the median number of red blood cell units transfused during the first year of treatment decreased by 82%, compared with the 6 months prior to treatment (9.0 vs. 0 units), and median iron infusions decreased by 70% during the same period (8.0 vs. 2.0 infusions), he said, adding that these improvements occurred within the first 6 months of treatment and were maintained through 12 months.
Study subjects were adults with a mean age of 63 years who were treated with systemic bevacizumab, a vascular endothelial growth factor receptor (VEGF) monoclonal antibody, between 2011 and 2019 for the primary indication of moderate to severe chronic HHT-related bleeding and anemia. Treatment involved four to eight induction infusions – typically at a dose of 5 mg/kg and given 4 weeks apart – followed by bevacizumab maintenance, either as continuous or scheduled maintenance at 4-, 8-, or 12-week intervals regardless of symptoms, or on an as-needed basis, with 2-6 infusions for signs or symptoms of rebleeding.
Patients received a median of 11 infusions, and 181 received maintenance treatment, including continuous or scheduled maintenance in 136 patients and as-needed maintenance in 45 patients, Dr. Al-Samkari said.
The treatment was generally well tolerated; the most common adverse events during 344 patient-years of treatment were hypertension, fatigue, and proteinuria. No fatal treatment-related adverse events occurred, and no increase in adverse events occurred with longer treatment, he noted
Venous thromboembolism occurred in five patients, including two patients who had “provoked events immediately following joint replacement surgery,” he said.
Thirteen patients (5%) discontinued treatment – 11 for inadequate effect and 2 for side effects, he noted.
Subgroup analyses showed that outcomes were similar regardless of underlying pathogenic mutation, but among those receiving bevacizumab maintenance, the continuous approach, compared with as-needed maintenance, was associated with greater improvement in hemoglobin (10.8 vs. 12.3 g/dL) and ESS (mean, 4.96 vs. 2.88) during months 7-12 of treatment, “which is the time most reflective of the effect of maintenance,” he said.
HHT, also known as Osler-Weber-Rendu disease, is a “rare, genetic, progressive, multisystem bleeding disorder resulting from disorder of angiogenesis,” Dr. Al-Samkari explained, adding that the condition is characterized by severe, recurrent epistaxis and chronic gastrointestinal bleeding.
“Bleeding frequently leads to iron deficiency anemia, which may be severe and dependent on regular iron infusions and/or blood transfusions,” he said.
Though rare, it is the second most common bleeding disorder worldwide, with a prevalence about twice that of hemophilia A and six times that of hemophilia B.
“Despite this, it has no FDA-approved therapies,” he said. “The current mainstay of care is surgical or procedural local hemostatic intervention – which is usually temporizing – and hematological support in the form of blood and iron.”
However, given that the underlying genetic defects that cause HHT result in elevations in VEGF, targeting VEGF with existing antiangiogenic agents is a promising approach.
In fact, several centers have been using bevacizumab for several years as an off-label treatment for bleeding in this setting, and while scattered case reports and small case series suggest efficacy, no “large or definitive studies” have been conducted, and safety hasn’t been carefully evaluated, he said.
To that end, the International Hereditary Hemorrhagic Telangiectasia Intravenous Bevacizumab Investigative Team (InHIBIT) was formed. The current report, “the largest study of antiangiogenic therapy to date in HHT,” represents the results of the InHIBIT-Bleed study, the first completed by the team. The next study will address bevacizumab for the treatment of high-output cardiac failure in HHT (the InHIBIT-HF study), Dr. Al-Samkari said.
Though limited by its retrospective nature and lack of a unified treatment protocol, the InHIBIT-Bleed study provides important information and is strengthened by the large cohort size, especially given that HHT is a rare disease, and by other factors, such as the substantial number of patient-years of treatment.
“Bevacizumab was effective in the management of severe HHT-related epistaxis and GI bleeds,” he said, noting the “significant and striking improvements” on a variety of measures.
Questioned about the durability of treatment effects after treatment discontinuation, Dr. Al-Samkari said outcomes are variable, “highly patient dependent,” and “something that we really need to investigate thoroughly.”
As for the potential for anti-VEGF therapy for bleeding in certain non-HHT settings, session moderator Michael Makris, MD, professor of haemostasis and thrombosis at the University of Sheffield, England, said the possibilities are intriguing.
“I work with lots of patients with von Willebrand disease and angiodysplasia,” he said, adding that angiodysplasia-related bleeding in type 2A von Willebrand disease is a major issue.
Dr. Al-Samkari agreed that the possibility is worth exploring.
“We have looked at this in a small number of patients, and the jury is still out,” he said. “But there is a publication in Gastroenterology – Albitar et al. – that evaluated bevacizumab in patients without HHT [who had] angiodysplasias from other causes – not specifically in type 2 von Willebrand syndrome ... and did find that it was effective at causing the angiodysplasias to regress, hemoglobin to improve.
“So the non-HHT use of this agent is certainly an important one [and] we do have retrospective evidence in a small group of patients who don’t have HHT, who do have angiodysplasias and bleeding, that it may be effective as well.”
Dr. Al-Samkari reported receiving research support and/or consulting fees from Agios, Amgen, and Dova.
SOURCE: Al-Samkari H et al. ISTH 2020, Abstract OC 09.2.
FROM THE 2020 ISTH CONGRESS
Microbiome research ‘opening doors’ to new Alzheimer’s disease treatments
Research into the microbiome is yielding some positive new potential treatment options for Alzheimer’s disease, according to George T. Grossberg, MD.
“I think the growing focus on the gut-brain axis is opening doors to new Alzheimer’s disease and other brain disorders, and I think the first of a possible future generation of compounds for prevention or treatment of Alzheimer’s disease may indeed be emerging,” Dr. Grossberg said at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Focus on the microbiome and microbiota is “a really hot, really new, really emerging area,” said Dr. Grossberg, professor in the department of psychiatry & behavioral neuroscience at Saint Louis University. But the microbiota, which is the microorganisms within a specific organ such as the colon, is sometimes confused with the microbiome – which is defined as all of the bacteria, viruses, fungi and other microorganisms within a habitat as well as their genomes and the environment around them. “These are often used interchangeably, but they’re not the same,” Dr. Grossberg said at the meeting, presented by Global Academy for Medical Education.
A person’s microbiome is unique to them, and nearly all of the microbiome is contained in the gut. A reduction in diversity of the microbiota in the digestive system has been linked to a wide variety of diseases, Dr. Grossberg explained. Conversely, a microbial imbalance or dysbiosis has been implicated in anxiety and/or depression, dementia, and certain cancers, he noted.
Bacteria that positively affect the microbiome come from two main genera: Lactobacillus and Bifidobacterium. Factors such as diet, medications, geography, stage of life, birthing process, infant feeding method, and stress can all affect a person’s microbiome. “We’re all beginning to understand that trying to manage or trying to diversify, trying to manipulate the microbiota may have a lot of remote effects – even effects on weight or diabetes, or other disorders,” Dr. Grossberg said.
Fecal microbiota transplantation (FMT), or the process of administering a donor’s fecal matter into a recipient’s intestinal tract, has proved beneficial in improving the health of patients suffering from recurrent Clostridioides difficile infection. A recent Harvard Health Letter, written by Jessica Allegretti, MD, MPH, observed that FMT is standard of care for patients with C. diff, and the procedure has a success rate of between 80% and 90%.
“It shows us very directly, in a very practical way, how addressing the dysbiosis – the imbalance of the gut microbiome – by infusing healthy bacteria may make a potential lifesaving difference,” Dr. Grossberg said.
Research is beginning to show that the link between gut microbiota and health extends to Alzheimer’s disease as well. Within the last few years, “we’ve started to understand that the microbial diversity in Alzheimer’s disease versus healthy age-matched controls is decreased,” Dr. Grossberg said.
In a study published by Nicholas M. Vogt and colleagues, there was decreased fecal microbial diversity among individuals with Alzheimer’s, compared with healthy individuals matched for age. Another study by Ping Liu, PhD, and colleagues found that patients with Alzheimer’s disease had decreased fecal microbial diversity, compared with individuals who had pre-onset amnestic mild cognitive impairment and normal cognition.
Dr. Grossberg noted that, while these studies do not prove that less fecal microbial diversity is responsible for mild cognitive impairment or Alzheimer’s disease, “it makes us think that, maybe, there’s a contributing factor.”
“What happens with the dysbiosis of the gut microbiome is increased permeability of the epithelial area of the gut, which can then lead to the gut-brain axis dysregulation and may in fact allow the selective entry of bacteria into the central nervous system because the blood-brain barrier comes to be dysfunctional,” he said.
Early evidence suggests that the gut-brain axis can affect cognition. In an animal model study, transferring the microbiota of a mouse with Alzheimer’s disease to one that had been bred to be germ-free resulted in cognitive decline – but there was no cognitive decline for germ-free mice that received a microbiota transplant from a mouse in a healthy control group. Results from another animal study showed that transferring healthy microbiota from a mouse model into a mouse with Alzheimer’s disease reduces amyloid and tau pathology. “The conclusions of these studies seems to be that microbiota mediated intestinal and systemic immune changes or aberrations seem to contribute to the pathogenesis of Alzheimer’s disease in these mouse models,” Dr. Grossberg said. “Consequently, restoring the gut microbial homeostasis may have beneficial effects on Alzheimer’s disease treatment.”
Periodontal disease also might be linked to Alzheimer’s disease, Dr. Grossberg said. Several studies have shown gingipains secreted from Porphyromonas gingivalis, which contribute to inflammation in the brain, have been found in cadavers of patients with Alzheimer’s disease (Sci Adv. 2019 Jan 23;5[1]:eaau3333). “There’s reason to think that the same changes may be occurring in the human brain with periodontal disease,” he said.
The relationship also might extend to the gut microbiota and the central nervous system. “There seems to be a direct communication, a direct relationship between normal gut physiology and healthy central nervous system functioning, and then, when you have abnormal gut function, it may result in a variety of abnormal central nervous system functions,” Dr. Grossberg said.
Studies that have examined a relationship between Alzheimer’s disease and gut microbiota have highlighted the potential of probiotics and prebiotics as a method of restoring the gut microbiota (Aging [Albany NY]. 2020 Mar 31; 12[6]:5539-50). Probiotics are popularly sold in health food aisles of grocery stores, and prebiotics are available in foods such as yogurts, tempeh, sauerkraut, and kimchi, as well as in drinks such as Kombucha tea. The effectiveness of probiotics and prebiotics also are being examined in randomized, controlled trials in patients with mild cognitive decline and mild Alzheimer’s disease, Dr. Grossberg said. One therapy, Sodium oligomannate, a marine algae–derived oral oligosaccharide, has shown effectiveness in remodeling gut microbiota and has been approved in China to treat patients with mild or moderate Alzheimer’s disease. Currently, no approved gut microbiota therapies are approved in the United States to treat Alzheimer’s disease; however, encouraging use of a prebiotic, a probiotic, or a Mediterranean diet is something clinicians might want to consider for their patients.
“The fact that we’re studying these things has really led to the notion that it may not be a bad idea for people to consume these healthy bacteria in later life, either as a way to prevent or delay, or to treat Alzheimer’s disease,” Dr. Grossberg said. “There’s really no downside.”
Global Academy and this news organization are owned by the same parent company. Dr. Grossberg reported that he is a consultant for Acadia, Alkahest, Avanir, Axsome, Biogen, BioXcel, Karuna, Lundbeck, Otsuka, Roche, and Takeda; receives research support from the National Institute on Aging, Janssen, and Roche; performs safety monitoring for EryDel, Merck, and Newron; and serves on data monitoring committees for Avanex and ITI Therapeutics.
Research into the microbiome is yielding some positive new potential treatment options for Alzheimer’s disease, according to George T. Grossberg, MD.
“I think the growing focus on the gut-brain axis is opening doors to new Alzheimer’s disease and other brain disorders, and I think the first of a possible future generation of compounds for prevention or treatment of Alzheimer’s disease may indeed be emerging,” Dr. Grossberg said at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Focus on the microbiome and microbiota is “a really hot, really new, really emerging area,” said Dr. Grossberg, professor in the department of psychiatry & behavioral neuroscience at Saint Louis University. But the microbiota, which is the microorganisms within a specific organ such as the colon, is sometimes confused with the microbiome – which is defined as all of the bacteria, viruses, fungi and other microorganisms within a habitat as well as their genomes and the environment around them. “These are often used interchangeably, but they’re not the same,” Dr. Grossberg said at the meeting, presented by Global Academy for Medical Education.
A person’s microbiome is unique to them, and nearly all of the microbiome is contained in the gut. A reduction in diversity of the microbiota in the digestive system has been linked to a wide variety of diseases, Dr. Grossberg explained. Conversely, a microbial imbalance or dysbiosis has been implicated in anxiety and/or depression, dementia, and certain cancers, he noted.
Bacteria that positively affect the microbiome come from two main genera: Lactobacillus and Bifidobacterium. Factors such as diet, medications, geography, stage of life, birthing process, infant feeding method, and stress can all affect a person’s microbiome. “We’re all beginning to understand that trying to manage or trying to diversify, trying to manipulate the microbiota may have a lot of remote effects – even effects on weight or diabetes, or other disorders,” Dr. Grossberg said.
Fecal microbiota transplantation (FMT), or the process of administering a donor’s fecal matter into a recipient’s intestinal tract, has proved beneficial in improving the health of patients suffering from recurrent Clostridioides difficile infection. A recent Harvard Health Letter, written by Jessica Allegretti, MD, MPH, observed that FMT is standard of care for patients with C. diff, and the procedure has a success rate of between 80% and 90%.
“It shows us very directly, in a very practical way, how addressing the dysbiosis – the imbalance of the gut microbiome – by infusing healthy bacteria may make a potential lifesaving difference,” Dr. Grossberg said.
Research is beginning to show that the link between gut microbiota and health extends to Alzheimer’s disease as well. Within the last few years, “we’ve started to understand that the microbial diversity in Alzheimer’s disease versus healthy age-matched controls is decreased,” Dr. Grossberg said.
In a study published by Nicholas M. Vogt and colleagues, there was decreased fecal microbial diversity among individuals with Alzheimer’s, compared with healthy individuals matched for age. Another study by Ping Liu, PhD, and colleagues found that patients with Alzheimer’s disease had decreased fecal microbial diversity, compared with individuals who had pre-onset amnestic mild cognitive impairment and normal cognition.
Dr. Grossberg noted that, while these studies do not prove that less fecal microbial diversity is responsible for mild cognitive impairment or Alzheimer’s disease, “it makes us think that, maybe, there’s a contributing factor.”
“What happens with the dysbiosis of the gut microbiome is increased permeability of the epithelial area of the gut, which can then lead to the gut-brain axis dysregulation and may in fact allow the selective entry of bacteria into the central nervous system because the blood-brain barrier comes to be dysfunctional,” he said.
Early evidence suggests that the gut-brain axis can affect cognition. In an animal model study, transferring the microbiota of a mouse with Alzheimer’s disease to one that had been bred to be germ-free resulted in cognitive decline – but there was no cognitive decline for germ-free mice that received a microbiota transplant from a mouse in a healthy control group. Results from another animal study showed that transferring healthy microbiota from a mouse model into a mouse with Alzheimer’s disease reduces amyloid and tau pathology. “The conclusions of these studies seems to be that microbiota mediated intestinal and systemic immune changes or aberrations seem to contribute to the pathogenesis of Alzheimer’s disease in these mouse models,” Dr. Grossberg said. “Consequently, restoring the gut microbial homeostasis may have beneficial effects on Alzheimer’s disease treatment.”
Periodontal disease also might be linked to Alzheimer’s disease, Dr. Grossberg said. Several studies have shown gingipains secreted from Porphyromonas gingivalis, which contribute to inflammation in the brain, have been found in cadavers of patients with Alzheimer’s disease (Sci Adv. 2019 Jan 23;5[1]:eaau3333). “There’s reason to think that the same changes may be occurring in the human brain with periodontal disease,” he said.
The relationship also might extend to the gut microbiota and the central nervous system. “There seems to be a direct communication, a direct relationship between normal gut physiology and healthy central nervous system functioning, and then, when you have abnormal gut function, it may result in a variety of abnormal central nervous system functions,” Dr. Grossberg said.
Studies that have examined a relationship between Alzheimer’s disease and gut microbiota have highlighted the potential of probiotics and prebiotics as a method of restoring the gut microbiota (Aging [Albany NY]. 2020 Mar 31; 12[6]:5539-50). Probiotics are popularly sold in health food aisles of grocery stores, and prebiotics are available in foods such as yogurts, tempeh, sauerkraut, and kimchi, as well as in drinks such as Kombucha tea. The effectiveness of probiotics and prebiotics also are being examined in randomized, controlled trials in patients with mild cognitive decline and mild Alzheimer’s disease, Dr. Grossberg said. One therapy, Sodium oligomannate, a marine algae–derived oral oligosaccharide, has shown effectiveness in remodeling gut microbiota and has been approved in China to treat patients with mild or moderate Alzheimer’s disease. Currently, no approved gut microbiota therapies are approved in the United States to treat Alzheimer’s disease; however, encouraging use of a prebiotic, a probiotic, or a Mediterranean diet is something clinicians might want to consider for their patients.
“The fact that we’re studying these things has really led to the notion that it may not be a bad idea for people to consume these healthy bacteria in later life, either as a way to prevent or delay, or to treat Alzheimer’s disease,” Dr. Grossberg said. “There’s really no downside.”
Global Academy and this news organization are owned by the same parent company. Dr. Grossberg reported that he is a consultant for Acadia, Alkahest, Avanir, Axsome, Biogen, BioXcel, Karuna, Lundbeck, Otsuka, Roche, and Takeda; receives research support from the National Institute on Aging, Janssen, and Roche; performs safety monitoring for EryDel, Merck, and Newron; and serves on data monitoring committees for Avanex and ITI Therapeutics.
Research into the microbiome is yielding some positive new potential treatment options for Alzheimer’s disease, according to George T. Grossberg, MD.
“I think the growing focus on the gut-brain axis is opening doors to new Alzheimer’s disease and other brain disorders, and I think the first of a possible future generation of compounds for prevention or treatment of Alzheimer’s disease may indeed be emerging,” Dr. Grossberg said at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Focus on the microbiome and microbiota is “a really hot, really new, really emerging area,” said Dr. Grossberg, professor in the department of psychiatry & behavioral neuroscience at Saint Louis University. But the microbiota, which is the microorganisms within a specific organ such as the colon, is sometimes confused with the microbiome – which is defined as all of the bacteria, viruses, fungi and other microorganisms within a habitat as well as their genomes and the environment around them. “These are often used interchangeably, but they’re not the same,” Dr. Grossberg said at the meeting, presented by Global Academy for Medical Education.
A person’s microbiome is unique to them, and nearly all of the microbiome is contained in the gut. A reduction in diversity of the microbiota in the digestive system has been linked to a wide variety of diseases, Dr. Grossberg explained. Conversely, a microbial imbalance or dysbiosis has been implicated in anxiety and/or depression, dementia, and certain cancers, he noted.
Bacteria that positively affect the microbiome come from two main genera: Lactobacillus and Bifidobacterium. Factors such as diet, medications, geography, stage of life, birthing process, infant feeding method, and stress can all affect a person’s microbiome. “We’re all beginning to understand that trying to manage or trying to diversify, trying to manipulate the microbiota may have a lot of remote effects – even effects on weight or diabetes, or other disorders,” Dr. Grossberg said.
Fecal microbiota transplantation (FMT), or the process of administering a donor’s fecal matter into a recipient’s intestinal tract, has proved beneficial in improving the health of patients suffering from recurrent Clostridioides difficile infection. A recent Harvard Health Letter, written by Jessica Allegretti, MD, MPH, observed that FMT is standard of care for patients with C. diff, and the procedure has a success rate of between 80% and 90%.
“It shows us very directly, in a very practical way, how addressing the dysbiosis – the imbalance of the gut microbiome – by infusing healthy bacteria may make a potential lifesaving difference,” Dr. Grossberg said.
Research is beginning to show that the link between gut microbiota and health extends to Alzheimer’s disease as well. Within the last few years, “we’ve started to understand that the microbial diversity in Alzheimer’s disease versus healthy age-matched controls is decreased,” Dr. Grossberg said.
In a study published by Nicholas M. Vogt and colleagues, there was decreased fecal microbial diversity among individuals with Alzheimer’s, compared with healthy individuals matched for age. Another study by Ping Liu, PhD, and colleagues found that patients with Alzheimer’s disease had decreased fecal microbial diversity, compared with individuals who had pre-onset amnestic mild cognitive impairment and normal cognition.
Dr. Grossberg noted that, while these studies do not prove that less fecal microbial diversity is responsible for mild cognitive impairment or Alzheimer’s disease, “it makes us think that, maybe, there’s a contributing factor.”
“What happens with the dysbiosis of the gut microbiome is increased permeability of the epithelial area of the gut, which can then lead to the gut-brain axis dysregulation and may in fact allow the selective entry of bacteria into the central nervous system because the blood-brain barrier comes to be dysfunctional,” he said.
Early evidence suggests that the gut-brain axis can affect cognition. In an animal model study, transferring the microbiota of a mouse with Alzheimer’s disease to one that had been bred to be germ-free resulted in cognitive decline – but there was no cognitive decline for germ-free mice that received a microbiota transplant from a mouse in a healthy control group. Results from another animal study showed that transferring healthy microbiota from a mouse model into a mouse with Alzheimer’s disease reduces amyloid and tau pathology. “The conclusions of these studies seems to be that microbiota mediated intestinal and systemic immune changes or aberrations seem to contribute to the pathogenesis of Alzheimer’s disease in these mouse models,” Dr. Grossberg said. “Consequently, restoring the gut microbial homeostasis may have beneficial effects on Alzheimer’s disease treatment.”
Periodontal disease also might be linked to Alzheimer’s disease, Dr. Grossberg said. Several studies have shown gingipains secreted from Porphyromonas gingivalis, which contribute to inflammation in the brain, have been found in cadavers of patients with Alzheimer’s disease (Sci Adv. 2019 Jan 23;5[1]:eaau3333). “There’s reason to think that the same changes may be occurring in the human brain with periodontal disease,” he said.
The relationship also might extend to the gut microbiota and the central nervous system. “There seems to be a direct communication, a direct relationship between normal gut physiology and healthy central nervous system functioning, and then, when you have abnormal gut function, it may result in a variety of abnormal central nervous system functions,” Dr. Grossberg said.
Studies that have examined a relationship between Alzheimer’s disease and gut microbiota have highlighted the potential of probiotics and prebiotics as a method of restoring the gut microbiota (Aging [Albany NY]. 2020 Mar 31; 12[6]:5539-50). Probiotics are popularly sold in health food aisles of grocery stores, and prebiotics are available in foods such as yogurts, tempeh, sauerkraut, and kimchi, as well as in drinks such as Kombucha tea. The effectiveness of probiotics and prebiotics also are being examined in randomized, controlled trials in patients with mild cognitive decline and mild Alzheimer’s disease, Dr. Grossberg said. One therapy, Sodium oligomannate, a marine algae–derived oral oligosaccharide, has shown effectiveness in remodeling gut microbiota and has been approved in China to treat patients with mild or moderate Alzheimer’s disease. Currently, no approved gut microbiota therapies are approved in the United States to treat Alzheimer’s disease; however, encouraging use of a prebiotic, a probiotic, or a Mediterranean diet is something clinicians might want to consider for their patients.
“The fact that we’re studying these things has really led to the notion that it may not be a bad idea for people to consume these healthy bacteria in later life, either as a way to prevent or delay, or to treat Alzheimer’s disease,” Dr. Grossberg said. “There’s really no downside.”
Global Academy and this news organization are owned by the same parent company. Dr. Grossberg reported that he is a consultant for Acadia, Alkahest, Avanir, Axsome, Biogen, BioXcel, Karuna, Lundbeck, Otsuka, Roche, and Takeda; receives research support from the National Institute on Aging, Janssen, and Roche; performs safety monitoring for EryDel, Merck, and Newron; and serves on data monitoring committees for Avanex and ITI Therapeutics.
FROM CP/AACP PSYCHIATRY UPDATE