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Booster shot back-and-forth creates uncertainty, confusion
Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.
, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.
The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.
“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.
This kind of mixed messaging is generating more questions than answers.
“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.
When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”
“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association.
Boosting misinformation?
“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.
Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”
These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.
“That’s unfortunate because it’s a complete fallacy.”
Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”
“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.
More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
‘Gaming the system’
Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.
“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.
To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.
“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”
“Some people are gaming the system to get their booster or second shot of J&J,” he said.
For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”
“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”
Dr. Edje is likewise seeing interest from some ineligible patients, she said.
Crossing a liability line?
Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.
“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”
Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.
But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.
The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.
“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.
“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
Despite confusion, demand is up
Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.
“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”
“There is quite a bit of excitement out there,” he said.
Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”
Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
‘Walk, don’t run’
To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.
“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.
CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.
“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.
“We will come and look at the data for Moderna and J&J in very short order.”
Dr. Edje and Mr. Caswell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.
, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.
The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.
“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.
This kind of mixed messaging is generating more questions than answers.
“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.
When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”
“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association.
Boosting misinformation?
“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.
Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”
These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.
“That’s unfortunate because it’s a complete fallacy.”
Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”
“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.
More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
‘Gaming the system’
Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.
“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.
To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.
“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”
“Some people are gaming the system to get their booster or second shot of J&J,” he said.
For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”
“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”
Dr. Edje is likewise seeing interest from some ineligible patients, she said.
Crossing a liability line?
Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.
“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”
Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.
But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.
The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.
“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.
“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
Despite confusion, demand is up
Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.
“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”
“There is quite a bit of excitement out there,” he said.
Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”
Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
‘Walk, don’t run’
To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.
“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.
CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.
“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.
“We will come and look at the data for Moderna and J&J in very short order.”
Dr. Edje and Mr. Caswell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.
, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.
The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.
“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.
This kind of mixed messaging is generating more questions than answers.
“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.
When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”
“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association.
Boosting misinformation?
“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.
Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”
These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.
“That’s unfortunate because it’s a complete fallacy.”
Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”
“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.
More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
‘Gaming the system’
Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.
“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.
To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.
“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”
“Some people are gaming the system to get their booster or second shot of J&J,” he said.
For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”
“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”
Dr. Edje is likewise seeing interest from some ineligible patients, she said.
Crossing a liability line?
Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.
“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”
Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.
But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.
The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.
“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.
“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
Despite confusion, demand is up
Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.
“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”
“There is quite a bit of excitement out there,” he said.
Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”
Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
‘Walk, don’t run’
To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.
“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.
CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.
“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.
“We will come and look at the data for Moderna and J&J in very short order.”
Dr. Edje and Mr. Caswell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
USPSTF updates diabetes recs, lowers screening age
REFERENCES
- US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
- American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002
REFERENCES
- US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
- American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002
REFERENCES
- US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
- American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002
SARS-CoV-2 Delta variant may double the risk for hospitalization
Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.
Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.
Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.
Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.
Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.
Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.
Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.
Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.
Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.
Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.
Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.
Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.
Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.
Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.
Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.
Novel trastuzumab duocarmazine significantly improved survival in advanced HER2-positive breast cancer
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
FROM ESMO 2021
Worsening motor function tied to post COVID syndrome in Parkinson’s disease
, new research suggests.
Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.
“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.
The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.
The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Long-term sequelae
Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.
Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.
The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”
Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.
Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.
Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
Symptom worsening
“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.
By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.
Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.
In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.
The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.
Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
Meaningful addition
Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.
“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.
He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.
“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.
Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.
“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.
The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.
“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.
The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.
The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Long-term sequelae
Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.
Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.
The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”
Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.
Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.
Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
Symptom worsening
“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.
By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.
Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.
In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.
The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.
Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
Meaningful addition
Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.
“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.
He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.
“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.
Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.
“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.
The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.
“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.
The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.
The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Long-term sequelae
Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.
Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.
The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”
Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.
Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.
Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
Symptom worsening
“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.
By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.
Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.
In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.
The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.
Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
Meaningful addition
Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.
“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.
He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.
“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.
Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.
“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.
The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM MDS VIRTUAL CONGRESS 2021
Pruritic blistering rash
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
Clinical Edge Journal Scan Commentary: Prostate Cancer October 2021
Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.
Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.
Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.
Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.
The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.
Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.
Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.
Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.
Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.
The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.
Radiation has long been a part of treatment for localized prostate cancer. However, radiation and radiation-delivery modalities continue to evolve to decrease toxicity without sacrificing efficacy, expand the roles of these modalities, and enhance efficacy of other concomitantly delivered treatment modalities. The accompanying studies describe efforts to those effects.
Hypofractionated delivery of radiation is now often considered preferred over conventionally fractionated radiation for localized prostate cancer to maintain efficacy while decreasing toxicity. To determine if the benefit of lower toxicity holds over time, Staffurth et al assessed patient-reported outcomes (PROs) in participants of the CHHiP trial where men were randomized to conventional radiation versus 2 alternative hypofraction schedules. At 5 years post-radiation, there were no significant differences amongst the 3 groups with respect to bowel bother, urinary bother, or sexual bother.
Evidence is emerging that stereotactic body radiation therapy (SBRT) has benefits for oligometastatic disease; however, studies are emerging that support the hypothesis that radiation may enhance immunotherapy in many cancers in the metastatic setting. Kwan et al evaluated the effects of a single fraction of SBRT administered to 1 or 2 disease sites before the first and second doses of avelumab (a PD-L1 antibody) in patients with metastatic castrate-resistant prostate cancer (with prior exposure to at least one second-generation androgen receptor inhibitor). In this single arm phase II study, the disease control rate was 48%, overall response rate was 31%, median radiographic progression-free survival (rPFS) was 8.4 months, and median overall survival (OS) was 14.1 months in this heavily pretreated group of 31 participants. As immunotherapy has been considered efficacious in select groups of prostate cancer (such as tumors with microsatellite instability), this study supports ongoing and new efforts to evaluate how to enhance immunotherapy against prostate cancer.
Radium-223 has been demonstrated to have efficacy in metastatic disease of the bone. Ongoing efforts to determine whether combined modality treatment in this setting may improve outcomes in metastatic disease, Maughn et al evaluated the combination of radium-223 and enzalutamide for safety and efficacy in a small and hypothesis-generating study 47 participants where 35 received enzalutamide plus radium-223 and 12 received enzlutamide alone. Of note, there were no increase in fractures (45 of the 47 participants received bone protective therapy, however), but there were no differences in the secondary endpoints of PSA-PFS, rPFS, or OS (primary endpoints of decline in bone metabolism markers were previously reported). This is a hypothesis generating study that supports the likely safety of this modality if bone protecting agents are utilized.
The 3 studies summarized here represent the ongoing evolution of radiation or radiation-delivery modalities in localized and metastatic prostate cancer. It is encouraging to see the ongoing evaluate of PROs over time, as long-term quality of life in patients potentially cured of disease is of utmost importance. In addition, efforts to evaluate radiation or radium-223 in widely metastatic disease as part of combination therapy may reveal not only situations with modest benefits in efficacy, but more importantly, may reveal molecular insights into newer treatment strategies.
Clinical Edge Journal Scan Commentary: HCC October 2021
Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.
Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.
For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively). The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.
Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.
Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.
Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.
For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively). The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.
Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.
Treatment of patients with hepatocellular carcinoma (HCC) requires a multidisciplinary approach. This month we will review articles that analyze outcomes after liver resection compared to percutaneous ablation, prediction of immunotherapy efficacy based on observed treatment-related side effects, and the risk of subsequent malignancies in patients with HCC.
Xie et al. reported their retrospective review of outcomes of 67 adults with resectable caudate HCC within Milan criteria. Out of these, 46 underwent hepatic resection and 21 underwent percutaneous ablation. Overall survival at 1, 3, and 5 years was 97.6%, 83.6%, and 71.5%, respectively, for the hepatic resection patients, vs 89.4%, 58.5%, and 48.8%, respectively, for the percutaneous ablation patients (P = 0.032). Recurrence-free survival at these time points was 77.6%, 47.9%, and 42.6%, respectively, for the hepatic resection group, and 40.5%, 23.2%, and 15.4%, respectively, for the percutaneous ablation group (P = 0.010). The investigators concluded that HCC patients who underwent hepatic resection had significantly higher rates of recurrence-free and overall survival compared to those who underwent percutaneous ablation.
For those patients with unresectable HCC, systemic immune checkpoint inhibitor therapy is now part of the standard of care. Treatment-associated adverse events occur in over half of patients treated with immunotherapy. Pinato et al. reviewed the outcomes of a cohort of 406 adults with unresectable or advanced HCC who were receiving immune checkpoint inhibitor therapy while enrolled in clinical trials that were submitted to the Food and Drug Administration. the development of adverse events was associated with longer overall survival and progression-free survival rates compared to patients who did not develop treatment-related adverse events (16.7 months vs 11.2 months; 5.5 months vs 2.2 months, respectively). The authors concluded that the development of treatment-related adverse events was significantly correlated with improve overall and progression-free survival in HCC patients treated with ICI monotherapy in clinical trials.
Finally, Kong et al. retrospectively looked at a cohort of 40,314 adult patients diagnosed with HCC between 2000 and 2014 in the SEER database, identifying the incidence of second primary cancers. Overall, the patients were followed for a median of 19 months following their HCC diagnosis. A total of 1,593 HCC patients (3.95%) developed secondary primary malignancies starting at 2 months after their initial HCC diagnosis. The 3-, 5-, and 10-year cumulative incidence of developing second primary malignancies were 2.35%, 3.12%, and 4.51%. The top five sites of the second primary malignancies were lung and bronchus, prostate, non-Hodgkin lymphoma, colon, and breast. The patients with poorer tumor-related characteristics such as larger tumor size, vascular invasion, positive AFP level, poorer tumor grade, and distant extension were associated with a decreased risk of developing second primary cancers, most probably because of their higher risk of dying from HCC. The authors developed a competing-risk nomogram for the purpose of improving guideline surveillance and further management of HCC survivors, concluding that HCC survivors should be monitored for evidence of secondary primary cancers.
COVID-19: Greater mortality among psych patients remains a mystery
Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.
The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.
The study was published online September 22 in JAMA Psychiatry.
Threefold increase in death
Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.
Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.
“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.
The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.
The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.
Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).
Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).
“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
Surprise finding
A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).
“This was a surprising finding,” said Dr. Nemani.
She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.
As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.
However, these factors are unlikely to fully account for the increased risk found in the study, she said.
“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.
Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.
“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.
The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.
“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.
The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.
The study was published online September 22 in JAMA Psychiatry.
Threefold increase in death
Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.
Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.
“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.
The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.
The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.
Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).
Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).
“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
Surprise finding
A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).
“This was a surprising finding,” said Dr. Nemani.
She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.
As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.
However, these factors are unlikely to fully account for the increased risk found in the study, she said.
“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.
Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.
“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.
The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.
“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.
The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.
The study was published online September 22 in JAMA Psychiatry.
Threefold increase in death
Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.
Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.
“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.
The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.
The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.
Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).
Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).
“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
Surprise finding
A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).
“This was a surprising finding,” said Dr. Nemani.
She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.
As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.
However, these factors are unlikely to fully account for the increased risk found in the study, she said.
“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.
Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.
“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.
The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.
“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fatigued absent of medical history
The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.
Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.
MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS.
Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.
Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ
Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme
The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.
Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.
MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS.
Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.
Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ
Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme
The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.
Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.
MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS.
Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.
Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ
Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme
A 51-year-old woman reports that she has been feeling fatigued despite the absence of any significant medical history. Although she usually walks to work, lately she has not had the energy to participate in her daily routine. She notes that over the past 2 weeks, colleagues have asked her if she is feeling well due to unusual ocular symptoms. She explains that several months ago she felt similarly unwell, with fatigue and generalized weakness, but her symptoms seemed to resolve. Upon presentation, she has diplopia on lateral gaze. MRI reveals lesions with high T2 signal intensity.
