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FDA inaction on hair loss drug’s suicide, depression, erectile dysfunction risk sparks lawsuit
Consumer advocacy group 4 years ago.
The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation.
As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.
Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.
The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.
“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.
Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.
“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.
The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online.
This news organization reached out to the FDA for comment but did not receive a response by press time.
A version of this article first appeared on Medscape.com.
Consumer advocacy group 4 years ago.
The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation.
As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.
Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.
The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.
“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.
Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.
“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.
The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online.
This news organization reached out to the FDA for comment but did not receive a response by press time.
A version of this article first appeared on Medscape.com.
Consumer advocacy group 4 years ago.
The September 2017 petition requested that the FDA take the popular hair-loss drug (1 mg finasteride, Propecia) off the market because of evidence of serious risk of patient injury, including depression and suicidal ideation.
As an alternative, PFSF requested that the FDA require the drug’s manufacturers revise the safety information on the labeling and add boxed warnings to disclose the potential for side effects, another of which is erectile dysfunction.
Public Citizen points to a recent analysis of the VigiBase global database, which tracks adverse effects from global pharmacovigilance agencies, lists 356 reports of suicidality and 2,926 reports of psychological adverse events in finasteride users. Yet, 4 years after submitting the petition, the FDA has neither granted nor denied it.
The lawsuit claims that FDA has acted unlawfully in failing to act on PFSF’s petition, and further cites “88 cases of completed suicide associated with finasteride use” per data from the VigiBase database.
“On the same day that PFSF submitted the petition, FDA’s docket management division acknowledged receipt and assigned the petition a docket number,” Michael Kirkpatrick, the Public Citizen attorney serving as lead counsel for PFSF, told this news organization.
Yet, to date, “there has been no substantive response to the petition. The lawsuit filed today seeks to force FDA to issue a decision on PFSF’s petition,” Mr. Kirkpatrick said.
“The FDA needs to act in a timely way to protect the public from the risks associated with use of Propecia. The FDA’s failure to act exposes consumers to potentially life-threatening harm,” he added in a statement.
The complaint filed today by Public Citizen in the U.S. District Court for the District of Columbia is available online.
This news organization reached out to the FDA for comment but did not receive a response by press time.
A version of this article first appeared on Medscape.com.
New European guidelines on CVD prevention
The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.
They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.
“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
Prevention at the individual and population levels
The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.
The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.
The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.
Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.
However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.
The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.
The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.
For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.
Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.
Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.
Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.
They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.
They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.
Potential cost issues that could be considered when implementing the guidelines are also reviewed.
Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
Setting the bar lower?
Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”
Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”
“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.
A version of this article first appeared on Medscape.com.
The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.
They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.
“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
Prevention at the individual and population levels
The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.
The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.
The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.
Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.
However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.
The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.
The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.
For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.
Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.
Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.
Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.
They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.
They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.
Potential cost issues that could be considered when implementing the guidelines are also reviewed.
Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
Setting the bar lower?
Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”
Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”
“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.
A version of this article first appeared on Medscape.com.
The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.
They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.
“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
Prevention at the individual and population levels
The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.
The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.
The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.
Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.
However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.
The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.
The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.
For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.
Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.
Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.
Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.
They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.
They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.
Potential cost issues that could be considered when implementing the guidelines are also reviewed.
Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
Setting the bar lower?
Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”
Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”
“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.
A version of this article first appeared on Medscape.com.
FROM ESC 2021
Teleintegrated versus telereferral care for complex psychiatric disorders
Two models for treating patients with complex psychiatric disorders in primary care are equally effective, new research suggests.
Results from a pragmatic, randomized comparative effectiveness study involving more than 1,000 patients showed that both integrated telepsychiatry collaborative care (TCC) and telepsychiatry/telepsychology enhanced referral (TER) provided “significantly and substantially” improved clinical outcomes, researchers noted.
However, the referral model required substantially more mental health specialist time than does the integrated model.
Therefore, ,” lead author John Fortney, PhD, department of psychiatry and behavioral sciences, University of Washington, Seattle, told this news organization.
The findings were published online Aug. 25 in JAMA Psychiatry.
Clinically meaningful improvement
The Study to Promote Innovation in Rural Integrated Telepsychiatry (SPIRIT) trial included 1,004 adults with untreated posttraumatic stress disorder and/or bipolar disorder. The participants were from 24 primary care clinics in rural and underserved areas in which there were no on-site psychiatrists or psychologists.
In SPIRIT, 508 patients were randomly allocated to TCC, and 496 were assigned to TER.
With TCC, an on-site behavioral health care manager and an off-site telepsychiatrist consultant support the primary care clinician in prescribing medications. With TER, an off-site telepsychiatrist prescribes medication, and an off-site telepsychologist delivers therapy.
The primary outcome was mental health functioning at 12 months, as measured by the Veterans RAND 12-item Health Survey Mental Component Summary (MCS) score. MSC scores range from 0 to 100.
Baseline MCS scores for the study participants were two standard deviations below the national average. The mean MCS scores were 39.7 and 41.2 in the TCC and TER groups, respectively.
There was no significant difference between TCC and TER in 12-month MCS score (beta = 1.0; 95% confidence interval, –0.8 to 2.8; P = .28). In addition, no significant differences in treatment effects were identified.
Patients in both groups experienced “large and clinically meaningful” improvements in MCS scores from baseline to 12 months (Cohen d = 0.81 and 0.90 for TCC and TER, respectively), the researchers report.
‘Bit of a surprise’
The comparative effectiveness of both models in this study was “a bit of a surprise,” Dr. Fortney noted.
“We hypothesized that TCC would have better outcomes than TER because we thought patients would be more likely to engage in treatment,” he said.
In collaborative care, the familiar primary care practitioner is the prescriber. The local care manager’s job is to keep patients engaged in care, said Dr. Fortney.
“However, because the medical school telemental health providers were privileged and credentialed to practice in the primary care clinic, the referral process to the telepsychiatrist and telepsychologist was much more successful than it usually is. So engagement was the same in both groups, and thus outcomes were equally as good,” Dr. Fortney said.
He noted that the referral model is used more than the collaborative care model “because it is similar to the more traditional approach to managing complex psychiatric disorders. I would say this is true both before and after COVID-19, but more so after.”
From a health care system perspective, “clinical leadership should implement whichever approach is most sustainable,” the investigators concluded.
Good news for clinics
Commenting on the study, Adam C. Powell, PhD, president of Payer+Provider Syndicate, said the “similar efficacy” of teleintegrated care and telereferral care for delivering behavioral health services in primary care is “good news for clinics,” because it suggests that clinicians may pick between the two modes of delivery and achieve similar outcomes.
“The resources available within a clinic may determine which of these approaches is most viable. The teleintegrated care approach requires the clinic to have more extensive resources locally,” Dr. Powell noted.
However, he pointed out that the study did not report relative costs of the two approaches, which may also be a factor in determining which one clinics choose to implement.
“Overall, the study shows that advances in telemedicine are making it possible for patients to access telepsychiatry and to achieve improvements in their mental health. Given the lack of access that many patients face, telepsychiatry offers one potential solution,” Dr. Powell concluded.
The SPIRIT study was funded by a grant from the Patient-Centered Outcomes Research Institute. Dr. Fortney and Dr. Powell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Two models for treating patients with complex psychiatric disorders in primary care are equally effective, new research suggests.
Results from a pragmatic, randomized comparative effectiveness study involving more than 1,000 patients showed that both integrated telepsychiatry collaborative care (TCC) and telepsychiatry/telepsychology enhanced referral (TER) provided “significantly and substantially” improved clinical outcomes, researchers noted.
However, the referral model required substantially more mental health specialist time than does the integrated model.
Therefore, ,” lead author John Fortney, PhD, department of psychiatry and behavioral sciences, University of Washington, Seattle, told this news organization.
The findings were published online Aug. 25 in JAMA Psychiatry.
Clinically meaningful improvement
The Study to Promote Innovation in Rural Integrated Telepsychiatry (SPIRIT) trial included 1,004 adults with untreated posttraumatic stress disorder and/or bipolar disorder. The participants were from 24 primary care clinics in rural and underserved areas in which there were no on-site psychiatrists or psychologists.
In SPIRIT, 508 patients were randomly allocated to TCC, and 496 were assigned to TER.
With TCC, an on-site behavioral health care manager and an off-site telepsychiatrist consultant support the primary care clinician in prescribing medications. With TER, an off-site telepsychiatrist prescribes medication, and an off-site telepsychologist delivers therapy.
The primary outcome was mental health functioning at 12 months, as measured by the Veterans RAND 12-item Health Survey Mental Component Summary (MCS) score. MSC scores range from 0 to 100.
Baseline MCS scores for the study participants were two standard deviations below the national average. The mean MCS scores were 39.7 and 41.2 in the TCC and TER groups, respectively.
There was no significant difference between TCC and TER in 12-month MCS score (beta = 1.0; 95% confidence interval, –0.8 to 2.8; P = .28). In addition, no significant differences in treatment effects were identified.
Patients in both groups experienced “large and clinically meaningful” improvements in MCS scores from baseline to 12 months (Cohen d = 0.81 and 0.90 for TCC and TER, respectively), the researchers report.
‘Bit of a surprise’
The comparative effectiveness of both models in this study was “a bit of a surprise,” Dr. Fortney noted.
“We hypothesized that TCC would have better outcomes than TER because we thought patients would be more likely to engage in treatment,” he said.
In collaborative care, the familiar primary care practitioner is the prescriber. The local care manager’s job is to keep patients engaged in care, said Dr. Fortney.
“However, because the medical school telemental health providers were privileged and credentialed to practice in the primary care clinic, the referral process to the telepsychiatrist and telepsychologist was much more successful than it usually is. So engagement was the same in both groups, and thus outcomes were equally as good,” Dr. Fortney said.
He noted that the referral model is used more than the collaborative care model “because it is similar to the more traditional approach to managing complex psychiatric disorders. I would say this is true both before and after COVID-19, but more so after.”
From a health care system perspective, “clinical leadership should implement whichever approach is most sustainable,” the investigators concluded.
Good news for clinics
Commenting on the study, Adam C. Powell, PhD, president of Payer+Provider Syndicate, said the “similar efficacy” of teleintegrated care and telereferral care for delivering behavioral health services in primary care is “good news for clinics,” because it suggests that clinicians may pick between the two modes of delivery and achieve similar outcomes.
“The resources available within a clinic may determine which of these approaches is most viable. The teleintegrated care approach requires the clinic to have more extensive resources locally,” Dr. Powell noted.
However, he pointed out that the study did not report relative costs of the two approaches, which may also be a factor in determining which one clinics choose to implement.
“Overall, the study shows that advances in telemedicine are making it possible for patients to access telepsychiatry and to achieve improvements in their mental health. Given the lack of access that many patients face, telepsychiatry offers one potential solution,” Dr. Powell concluded.
The SPIRIT study was funded by a grant from the Patient-Centered Outcomes Research Institute. Dr. Fortney and Dr. Powell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Two models for treating patients with complex psychiatric disorders in primary care are equally effective, new research suggests.
Results from a pragmatic, randomized comparative effectiveness study involving more than 1,000 patients showed that both integrated telepsychiatry collaborative care (TCC) and telepsychiatry/telepsychology enhanced referral (TER) provided “significantly and substantially” improved clinical outcomes, researchers noted.
However, the referral model required substantially more mental health specialist time than does the integrated model.
Therefore, ,” lead author John Fortney, PhD, department of psychiatry and behavioral sciences, University of Washington, Seattle, told this news organization.
The findings were published online Aug. 25 in JAMA Psychiatry.
Clinically meaningful improvement
The Study to Promote Innovation in Rural Integrated Telepsychiatry (SPIRIT) trial included 1,004 adults with untreated posttraumatic stress disorder and/or bipolar disorder. The participants were from 24 primary care clinics in rural and underserved areas in which there were no on-site psychiatrists or psychologists.
In SPIRIT, 508 patients were randomly allocated to TCC, and 496 were assigned to TER.
With TCC, an on-site behavioral health care manager and an off-site telepsychiatrist consultant support the primary care clinician in prescribing medications. With TER, an off-site telepsychiatrist prescribes medication, and an off-site telepsychologist delivers therapy.
The primary outcome was mental health functioning at 12 months, as measured by the Veterans RAND 12-item Health Survey Mental Component Summary (MCS) score. MSC scores range from 0 to 100.
Baseline MCS scores for the study participants were two standard deviations below the national average. The mean MCS scores were 39.7 and 41.2 in the TCC and TER groups, respectively.
There was no significant difference between TCC and TER in 12-month MCS score (beta = 1.0; 95% confidence interval, –0.8 to 2.8; P = .28). In addition, no significant differences in treatment effects were identified.
Patients in both groups experienced “large and clinically meaningful” improvements in MCS scores from baseline to 12 months (Cohen d = 0.81 and 0.90 for TCC and TER, respectively), the researchers report.
‘Bit of a surprise’
The comparative effectiveness of both models in this study was “a bit of a surprise,” Dr. Fortney noted.
“We hypothesized that TCC would have better outcomes than TER because we thought patients would be more likely to engage in treatment,” he said.
In collaborative care, the familiar primary care practitioner is the prescriber. The local care manager’s job is to keep patients engaged in care, said Dr. Fortney.
“However, because the medical school telemental health providers were privileged and credentialed to practice in the primary care clinic, the referral process to the telepsychiatrist and telepsychologist was much more successful than it usually is. So engagement was the same in both groups, and thus outcomes were equally as good,” Dr. Fortney said.
He noted that the referral model is used more than the collaborative care model “because it is similar to the more traditional approach to managing complex psychiatric disorders. I would say this is true both before and after COVID-19, but more so after.”
From a health care system perspective, “clinical leadership should implement whichever approach is most sustainable,” the investigators concluded.
Good news for clinics
Commenting on the study, Adam C. Powell, PhD, president of Payer+Provider Syndicate, said the “similar efficacy” of teleintegrated care and telereferral care for delivering behavioral health services in primary care is “good news for clinics,” because it suggests that clinicians may pick between the two modes of delivery and achieve similar outcomes.
“The resources available within a clinic may determine which of these approaches is most viable. The teleintegrated care approach requires the clinic to have more extensive resources locally,” Dr. Powell noted.
However, he pointed out that the study did not report relative costs of the two approaches, which may also be a factor in determining which one clinics choose to implement.
“Overall, the study shows that advances in telemedicine are making it possible for patients to access telepsychiatry and to achieve improvements in their mental health. Given the lack of access that many patients face, telepsychiatry offers one potential solution,” Dr. Powell concluded.
The SPIRIT study was funded by a grant from the Patient-Centered Outcomes Research Institute. Dr. Fortney and Dr. Powell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA approves first twice-yearly antipsychotic for schizophrenia
The U.S. Food and Drug Administration has approved a 6-month injection form of the long-acting atypical antipsychotic paliperidone palmitate (Invega Hafyera, Janssen Pharmaceuticals) for the treatment of schizophrenia in adults, the company has announced.
This marks the “first-and-only twice-yearly injectable” approved for treating schizophrenia, the company added in a press release.
Before transitioning to the 6-month form, patients must be adequately treated for a minimum of 4 months with the company’s 1-month formulation of paliperidone (Invega Sustenna), or with the 3-month version (Invega Trinza) for at least one 3-month injection cycle.
The FDA approved the twice-yearly formulation on the basis of results from a 12-month, randomized, double-blind, phase 3 study that enrolled 702 adults with schizophrenia from 20 countries.
“The phase 3 trial results provide compelling evidence that 6-month paliperidone palmitate offers longer-term symptom control with the fewest doses per year, which may support greater patient adherence,” Gustavo Alva, MD, medical director at ATP Clinical Research, Costa Mesa, Calif., and 6-month paliperidone palmitate clinical trial investigator, said in the release.
Noninferiority results
In the phase 3 trial, the twice-yearly version of the drug proved noninferior to the 3-month version on the primary endpoint of time to first relapse at the end of 12 months, with 92.5% and 95% of patients, respectively, relapse-free at 12 months.
Relapse was defined as psychiatric hospitalization, increase in Positive and Negative Syndrome Scale (PANSS) total score, increase in individual PANSS item scores, self-injury, violent behavior, or suicidal/homicidal ideation.
The safety profile observed in the trial was in line with prior studies of the 1-month and 3-month versions, with no new safety signals, the researchers note.
The most common adverse reactions affecting at least 5% of participants in the clinical trial receiving twice-year paliperidone were upper respiratory tract infection (12%), injection site reaction (11%), weight gain (9%), headache (7%), and parkinsonism (5%).
Relapse is common in adults with schizophrenia, often because of missed doses of medication, the company said in the news release.
, while research continues to demonstrate that stronger medication adherence means better patient outcomes,” Dr. Alva said.
Recently updated evidence-based guidelines from the American Psychiatric Association recommend consideration of long-acting injectables for appropriate adults living with schizophrenia.
“Long-acting injectable treatments offer a number of advantages, compared to oral medication for schizophrenia, including relief from needing to remember to take medication daily, lower discontinuation rates, and sustained treatment over longer periods,” Bill Martin, PhD, with Janssen Research & Development, said in the release.
“Today’s approval enables us to rethink how we manage this chronic disease by offering patients and caregivers the potential for a life less defined by schizophrenia medication,” Dr. Martin added.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved a 6-month injection form of the long-acting atypical antipsychotic paliperidone palmitate (Invega Hafyera, Janssen Pharmaceuticals) for the treatment of schizophrenia in adults, the company has announced.
This marks the “first-and-only twice-yearly injectable” approved for treating schizophrenia, the company added in a press release.
Before transitioning to the 6-month form, patients must be adequately treated for a minimum of 4 months with the company’s 1-month formulation of paliperidone (Invega Sustenna), or with the 3-month version (Invega Trinza) for at least one 3-month injection cycle.
The FDA approved the twice-yearly formulation on the basis of results from a 12-month, randomized, double-blind, phase 3 study that enrolled 702 adults with schizophrenia from 20 countries.
“The phase 3 trial results provide compelling evidence that 6-month paliperidone palmitate offers longer-term symptom control with the fewest doses per year, which may support greater patient adherence,” Gustavo Alva, MD, medical director at ATP Clinical Research, Costa Mesa, Calif., and 6-month paliperidone palmitate clinical trial investigator, said in the release.
Noninferiority results
In the phase 3 trial, the twice-yearly version of the drug proved noninferior to the 3-month version on the primary endpoint of time to first relapse at the end of 12 months, with 92.5% and 95% of patients, respectively, relapse-free at 12 months.
Relapse was defined as psychiatric hospitalization, increase in Positive and Negative Syndrome Scale (PANSS) total score, increase in individual PANSS item scores, self-injury, violent behavior, or suicidal/homicidal ideation.
The safety profile observed in the trial was in line with prior studies of the 1-month and 3-month versions, with no new safety signals, the researchers note.
The most common adverse reactions affecting at least 5% of participants in the clinical trial receiving twice-year paliperidone were upper respiratory tract infection (12%), injection site reaction (11%), weight gain (9%), headache (7%), and parkinsonism (5%).
Relapse is common in adults with schizophrenia, often because of missed doses of medication, the company said in the news release.
, while research continues to demonstrate that stronger medication adherence means better patient outcomes,” Dr. Alva said.
Recently updated evidence-based guidelines from the American Psychiatric Association recommend consideration of long-acting injectables for appropriate adults living with schizophrenia.
“Long-acting injectable treatments offer a number of advantages, compared to oral medication for schizophrenia, including relief from needing to remember to take medication daily, lower discontinuation rates, and sustained treatment over longer periods,” Bill Martin, PhD, with Janssen Research & Development, said in the release.
“Today’s approval enables us to rethink how we manage this chronic disease by offering patients and caregivers the potential for a life less defined by schizophrenia medication,” Dr. Martin added.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved a 6-month injection form of the long-acting atypical antipsychotic paliperidone palmitate (Invega Hafyera, Janssen Pharmaceuticals) for the treatment of schizophrenia in adults, the company has announced.
This marks the “first-and-only twice-yearly injectable” approved for treating schizophrenia, the company added in a press release.
Before transitioning to the 6-month form, patients must be adequately treated for a minimum of 4 months with the company’s 1-month formulation of paliperidone (Invega Sustenna), or with the 3-month version (Invega Trinza) for at least one 3-month injection cycle.
The FDA approved the twice-yearly formulation on the basis of results from a 12-month, randomized, double-blind, phase 3 study that enrolled 702 adults with schizophrenia from 20 countries.
“The phase 3 trial results provide compelling evidence that 6-month paliperidone palmitate offers longer-term symptom control with the fewest doses per year, which may support greater patient adherence,” Gustavo Alva, MD, medical director at ATP Clinical Research, Costa Mesa, Calif., and 6-month paliperidone palmitate clinical trial investigator, said in the release.
Noninferiority results
In the phase 3 trial, the twice-yearly version of the drug proved noninferior to the 3-month version on the primary endpoint of time to first relapse at the end of 12 months, with 92.5% and 95% of patients, respectively, relapse-free at 12 months.
Relapse was defined as psychiatric hospitalization, increase in Positive and Negative Syndrome Scale (PANSS) total score, increase in individual PANSS item scores, self-injury, violent behavior, or suicidal/homicidal ideation.
The safety profile observed in the trial was in line with prior studies of the 1-month and 3-month versions, with no new safety signals, the researchers note.
The most common adverse reactions affecting at least 5% of participants in the clinical trial receiving twice-year paliperidone were upper respiratory tract infection (12%), injection site reaction (11%), weight gain (9%), headache (7%), and parkinsonism (5%).
Relapse is common in adults with schizophrenia, often because of missed doses of medication, the company said in the news release.
, while research continues to demonstrate that stronger medication adherence means better patient outcomes,” Dr. Alva said.
Recently updated evidence-based guidelines from the American Psychiatric Association recommend consideration of long-acting injectables for appropriate adults living with schizophrenia.
“Long-acting injectable treatments offer a number of advantages, compared to oral medication for schizophrenia, including relief from needing to remember to take medication daily, lower discontinuation rates, and sustained treatment over longer periods,” Bill Martin, PhD, with Janssen Research & Development, said in the release.
“Today’s approval enables us to rethink how we manage this chronic disease by offering patients and caregivers the potential for a life less defined by schizophrenia medication,” Dr. Martin added.
A version of this article first appeared on Medscape.com.
Long COVID symptoms can persist for more than 1 year, study shows
Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.
The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.
Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report.
The study was published online Aug. 28 in The Lancet.
“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.
“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.
“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.
“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
Study details
Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.
Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.
Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.
Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.
Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).
At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.
Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients.
Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.
Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.
Mental health hit
Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.
Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.
As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).
Compared with men, women were twice as likely to report anxiety or depression.
“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.
“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.
The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).
The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”
“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.
“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.
The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.
The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.
Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report.
The study was published online Aug. 28 in The Lancet.
“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.
“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.
“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.
“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
Study details
Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.
Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.
Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.
Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.
Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).
At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.
Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients.
Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.
Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.
Mental health hit
Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.
Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.
As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).
Compared with men, women were twice as likely to report anxiety or depression.
“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.
“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.
The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).
The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”
“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.
“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.
The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.
The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.
Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report.
The study was published online Aug. 28 in The Lancet.
“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.
“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.
“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.
“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
Study details
Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.
Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.
Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.
Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.
Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).
At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.
Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients.
Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.
Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.
Mental health hit
Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.
Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.
As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).
Compared with men, women were twice as likely to report anxiety or depression.
“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.
“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.
The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).
The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”
“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.
“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.
The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
FDA OKs IV Briviact for seizures in kids as young as 1 month
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
Children’s upper airways primed to combat SARS-CoV-2 infection
Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.
The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.
The study was published online Aug. 18 in Nature Biotechnology.
Primed for action
Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.
A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.
“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release.
Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.
This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.
Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
‘Clear evidence’
The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.
Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.
Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.
Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”
“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.
“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.
“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.
The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.
The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.
The study was published online Aug. 18 in Nature Biotechnology.
Primed for action
Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.
A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.
“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release.
Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.
This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.
Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
‘Clear evidence’
The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.
Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.
Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.
Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”
“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.
“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.
“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.
The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.
The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.
The study was published online Aug. 18 in Nature Biotechnology.
Primed for action
Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.
A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.
“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release.
Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.
This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.
Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
‘Clear evidence’
The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.
Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.
Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.
Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”
“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.
“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.
“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.
The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Human brain patterns may help build a better AI system
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MACHINE INTELLIGENCE
Novel mutation may be unrecognized cause of sudden infant death
A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.
SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.
“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.
“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.
Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
Case details
The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.
When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.
The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.
In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report.
With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.
The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.
Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.
The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.
A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.
The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.
There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.
Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.
Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.
Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.
However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.
This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.
SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.
“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.
“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.
Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
Case details
The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.
When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.
The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.
In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report.
With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.
The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.
Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.
The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.
A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.
The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.
There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.
Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.
Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.
Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.
However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.
This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.
SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.
“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.
“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.
Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
Case details
The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.
When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.
The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.
In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report.
With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.
The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.
Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.
The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.
A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.
The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.
There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.
Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.
Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.
Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.
However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.
This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Two patients with metastatic lung cancer are disease-free for 1.5 years after TILs
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.
The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.
Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”
The study was published online in Nature Medicine.
A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.
The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.
TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.
The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.
“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.
The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.
Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.
One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.
“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.
This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.
“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.
In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment.
The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.
“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
‘Yeoman’s effort’ paving the way forward
Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”
“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.
He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”
“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.
“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.
All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.
The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group. A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.
The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.
Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”
The study was published online in Nature Medicine.
A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.
The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.
TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.
The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.
“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.
The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.
Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.
One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.
“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.
This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.
“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.
In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment.
The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.
“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
‘Yeoman’s effort’ paving the way forward
Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”
“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.
He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”
“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.
“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.
All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.
The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group. A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.
The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.
Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”
The study was published online in Nature Medicine.
A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.
The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.
TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.
The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.
“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.
The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.
Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.
One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.
“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.
This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.
“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.
In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment.
The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.
“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
‘Yeoman’s effort’ paving the way forward
Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”
“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.
He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”
“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.
“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.
All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.
The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group. A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.