An interim analysis of the DAYBREAK open-label extension trial found that the sphingosine-1-phosphate receptor agonist ozanimod achieved sustained control of disease activity in people with relapsing multiple sclerosis (RMS) even during the pandemic. The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.

Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.

The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.

“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.

Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.

“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
 

Stable efficacy and no worsening of COVID-19 outcomes

Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.

The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.

Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.

Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.

Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).

Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
 

Encouraging data

The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.

She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.

The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

An interim analysis of the DAYBREAK open-label extension trial found that the sphingosine-1-phosphate receptor agonist ozanimod achieved sustained control of disease activity in people with relapsing multiple sclerosis (RMS) even during the pandemic. The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.

Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.

The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.

“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.

Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.

“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
 

Stable efficacy and no worsening of COVID-19 outcomes

Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.

The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.

Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.

Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.

Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).

Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
 

Encouraging data

The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.

She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.

The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

An interim analysis of the DAYBREAK open-label extension trial found that the sphingosine-1-phosphate receptor agonist ozanimod achieved sustained control of disease activity in people with relapsing multiple sclerosis (RMS) even during the pandemic. The study began in 2020 and also captured data on COVID-19 infections, and found that most were mild and resembled the profile of COVID-19 infections in the broader MS population.

Ozanimod is approved for the treatment of relapsing MS (RMS) and moderately to severe ulcerative colitis.

The DAYBREAK trial revealed a safety profile that broadly matched what was seen in the pivotal studies, with the exception that one case of progressive multifocal leukoencephalopathy (PML) emerged in the study population.

“So now we do know that ozanimod can cause PML, just as fingolimod can cause PML. I think some of us were hoping that perhaps the extent of immune suppression was going to be somewhat different in ozanimod and that PML might not occur. It’s a rare complication, but one that we now know can occur with this drug,” Bruce Cree, MD, PhD, said in an interview.

Ozanimod is a more selective drug than fingolimod. It affects only cell surface expression of the S1P1 and S1P5 receptors, and not other known S1P receptors. Ozanimod does not require first-dose observation and cardiac monitoring in most patients, and it can be taken at home.

“The two products have not been compared head-to-head. This is all comparison of data from different studies, and one has to take those considerations in mind as important caveats. But generally speaking, the safety profile and tolerability profile of ozanimod seems to be a little bit better, in my opinion, compared to that of fingolimod,” said Dr. Cree, who presented the results of the study at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). He is professor of neurology at the University of California, San Francisco.
 

Stable efficacy and no worsening of COVID-19 outcomes

Among 2,181 participants in DAYBREAK who were at risk of COVID-19, 8.7% had confirmed or suspected cases of COVID-19 during the study period. All were unvaccinated. Fourteen cases were considered serious, and there were two COVID-19–related deaths, and a third death caused by a pulmonary abscess related to an earlier COVID-19 infection. “When you look at this data and compare it to other datasets, this is not too dissimilar from rates of mortality that we would expect or serious infection that we see in other MS cohorts. So there doesn’t seem to be a striking worsening of COVID outcomes with ozanimod,” said Dr. Cree.

The benefit of the drug appeared to remain stable over multiple years. The annualized relapse rate was low and the relapse rate appeared to decline further over time. “It’s not an absolutely flat line, there is some curvature to it. So that that’s good news as well. And then the objective observation of lesion formation also is attenuated over time. We see a therapeutic effect on new radiographic lesions as well, and very low rates of disability worsening in ozanimod patients,” said Dr. Cree.

Overall, the study included 2,494 patients who entered the open-label extension study of the phase 1-3 trials. The study began in November 2019, and the current data extend through May 10, 2021. A total of 736 patients started out with interferon beta-1a and later switched to 0.92 mg ozanimod, 877 patients started at 0.46 mg ozanimod and switched to 0.92 mg ozanimod, and 881 were on a continuous dose of 0.92 mg ozanimod.

Three-quarters of the patients were relapse free at 36 months, 71% at 48 months. Among those who were on 0.92 mg ozanimod continuously, 64% were relapse-free through 60 months of treatment.

Among the cohort, 7.6% experienced severe treatment-emergent adverse events (TEAEs), 11.9% experienced serious TEAEs, and 3.0% discontinued ozanimod because of TEAEs. Common TEAEs included nasopharyngitis (59.3%), headache (46.1%), upper respiratory tract infection (31.5%), lymphopenia (29.4%), decreased absolute lymphocyte count (ALC, 24.5%), back pain (22.7%), and hypertension (20.7%).

Furthermore, 1.4% of patients developed treatment-emergent malignancies, 0.4% developed macular edema, 2.8% had cardiac TEAEs, and 9.8% had ALC levels below 0.2 x 109/L.
 

Encouraging data

The COVID-19 data were encouraging, according to Patricia Coyle, MD, who was asked to comment on the study. “190 individuals out of 2,181 seems quite reasonable, and they had three deaths. It certainly didn’t look like any excessive numbers of COVID, or excessive numbers of deaths,” said Dr. Coyle, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center.

She noted that other database studies have shown an association between increased risk and anti-CD20 agents, but they haven’t really seen that with the other disease-modifying therapies. “I think this is some long-term data that says that ozanimod appears to be well tolerated without having any surprising late toxicity,” said Dr. Coyle.

The study was funded by Celgene International II. Dr. Cree has consulted for Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini, and received grant support from Genentech. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.

The past week has seen heated debate about the complex issue of how to best treat children with gender dysphoria, with further developments in a number of U.S. states and in Sweden. 

In the U.S., more states have moved to prevent the use of any medical treatment, such as puberty blockers or cross-sex hormones, in kids younger than the age of 18, most recently in a state Senate vote in Alabama last week, and in Texas, where Governor Greg Abbott is said to have ordered state agencies to investigate reports of gender-transition procedures on children as “child abuse.”

At least one parent has, because of this, established a crowdfunding page to try to raise money to move away from Texas, fearful of being accused of child abuse if their child with gender dysphoria receives hormone therapy. And a countersuit has been filed there by the ACLU of Texas and Lambda Legal, a civil rights organization, on behalf of one parent said to be under investigation.

But on the flip side, parents living in more liberal states – where children under the age of 18 can often get hormones to transition without parental consent – are considering moving out of them to protect their children. These parents are concerned that their kids do not know enough about the side effects of puberty blockers, or lifetime use of cross-sex hormones and its implications, to be able to make properly informed decisions at such a young age.  

Meanwhile, Sweden has further tightened its restrictions on medical therapy to treat gender-questioning kids, with a recent announcement from its National Board of Health and Welfare (NBHW), on Feb. 22, urging restraint in hormone treatment of minors with gender dysphoria following a review by the agency there that assesses health technologies, the SBU.

Based on the review results, the NBHW’s overall conclusion is that the risks of puberty blocking and cross-sex hormone treatment for those under 18 currently outweigh the possible benefits for the group as a whole. The agency now says hormone treatment should only be offered in exceptional cases outside the framework of research, and principally, only in adolescents with childhood-onset gender dysphoria, as opposed to those who develop it during puberty, or in their teens, as is the case with most teenagers currently presenting. 

At the same time, gender-affirming hormone treatment for adolescents who identify as transgender or nonbinary is associated with changes in depression and suicidality, according to a new U.S. survey published Feb. 25 in JAMA Network Health. 

However, experts who spoke to this news organization were critical of the study, noting it was small, conducted in just 104 youth who were an average age of 15.8 years and of whom only 63% completed the survey at the final timepoint, just 1 year after starting therapy. In addition, there was no control group, among other limitations.

“The most worrying thing is that they haven’t described the pros and cons of the treatment that they are researching. We know that there are risks inherent in using gender-affirming medicine, as with all medications,” Anna Hutchinson, DClinPsych, of the Integrated Psychology Clinic, London, told this news organization.

“For example, when people with gender dysphoria use cross-sex hormones, there is a burden of treatment that can last a lifetime, both for those who benefit from the treatment and those who detransition or regret later on,” said Dr. Hutchinson, who has extensive experience of working with young people with issues related to sexuality or gender.

“This isn’t mentioned at all, which makes the paper appear quite biased towards using one approach for managing gender dysphoria and related distress, whilst not acknowledging any risks of doing so or considering alternatives,” she noted.
 

Why were some treated with hormones while others weren’t? 

The newly published survey is by PhD student Diana M. Tordoff, MPH, of the Department of Epidemiology, University of Washington, Seattle, and colleagues. Published alongside was an invited commentary by Brett Dolotina, BS, of Massachusetts General Hospital, Boston, and Jack L. Turban, MD, MHS, of Stanford (Calif.) University.

The study was conducted at an urban multidisciplinary gender clinic in Seattle among transgender and nonbinary adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 to November 2021.

Participating in the study were 104 youths aged 13-20 years (mean age, 15.8 years), 63 transmasculine (born female) individuals (60.6%), 27 transfeminine (born male) individuals (26.0%), 10 nonbinary or gender-fluid individuals (9.6%), and four youths who responded, “I don’t know,” or did not respond to the gender-identity question (3.8%). 

At baseline, 59 individuals (56.7%) had moderate-to-severe depression, 52 individuals (50.0%) had moderate-to-severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. 

By the end of the study, 69 youths (66.3%) had received puberty blockers, cross-sex hormones (testosterone for girls transitioning to male and estrogen for boys transitioning to female), or both interventions, while 35 youths had not received either intervention (33.7%). 

After adjustment for temporal trends and potential confounders, there were a 60% lower odds of depression (adjusted odds ratio, 0.40; 95% confidence interval, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated puberty blockers or cross-sex hormones. 

There was no association between these treatments and anxiety, however (aOR, 1.01; 95% CI, 0.41-2.51).

Dr. Hutchinson points out that nonbinary and gender fluid “are not diagnostic or clinical terms,” adding, “there is no information about how the groups were chosen or if any of them met the criteria for gender dysphoria. It seems strange to not have measured gender dysphoria, both before and after interventions, in a group of children presenting with gender dysphoria.”

She adds: “I am questioning why ‘gender-affirming’ medicine appears to be being used here as a specific intervention for depression and suicidality? [That] wouldn’t usually be the first reason to commence these particular treatments. Why didn’t they provide therapy or antidepressant medication to this group of young people, as is routine for managing mood and/or suicidality in all other patient cohorts?”  

In their commentary, Mr. Dolotina and Dr. Turban observe: “The rate of suicidality among the Tordoff et al. sample after receiving gender-affirming care was still much higher than national rates of suicidality among youth in the U.S., denoting that ... other mental health determinants must be addressed ... including gender minority stress.”
 

Small study, no control group, large loss to follow-up

Dr. Hutchinson also criticizes the small sample size of just 104 youth and “large loss to follow-up, whereby only 65 of those 104 [youth] completed the final survey in a short time [1 year].” This could indicate “that only the most satisfied kids stayed the course,” she suggests. 

And importantly, the findings on depression and suicidality rely on the experience of only five people in the no-treatment group at 12 months, she points out. 

Also, as the authors themselves acknowledge, they didn’t control for other psychiatric medicines that the participants might have been taking at baseline.

“It’s important to know more about all of this in order to draw accurate conclusions about what works, or does not, for whom,” noted Dr. Hutchinson.

Most patients, too, she notes, were females-to-males taking testosterone. Therefore, the finding that they experienced a reduction in depression might simply reflect the widely reported antidepressant effects of testosterone. 

Also expressing concern about the small sample size and “lack of a control group” is Michelle Mackness, MC, a Canadian counselor in private practice who has experience working with gender-questioning individuals, detransitioners, and those experiencing complications related to their transition. 

“Tordoff et al.’s assertion that there is a ‘robust evidence base’ supporting pediatric transition seems out-of-step with recent global developments in care policies and protocols for gender-questioning youth,” she points out.

“Neither the study authors or commentators acknowledge, let alone address, the fact that Finland, the U.K., and Sweden have recently determined that the evidence allegedly supporting medical interventions for pediatric transition is ‘inconclusive’,” she adds. 

Asked to respond, Ms. Tordoff did not directly address this question. Rather, she reiterated to this news organization: “We found that receipt of puberty blockers and gender-affirming hormones was associated with a 60% lower odds of depression and a 73% lower odds of suicidal thoughts by the end of our study follow-up. We conducted extensive sensitivity analyses, which support the robustness of our study findings.”

She added: “These results are consistent with other recently published prospective cohort studies (please see citations provided within the manuscript).”

Parents may move states

It is this concern about the lifetime burden of treatment involved with transitioning that gives some parents of children with gender dysphoria pause for thought, especially those who live in more liberal U.S. states.

Indeed, two of America’s leading psychologists who work in this field, including one who is transgender herself, told this news organization in November they are now concerned about a lack of adequate psychological evaluations of youth with gender dysphoria before any medical treatment is considered. 

So while one parent, Violet A., last week established a GoFundMe page for her child, entitled, “Help Us Move Isa to Safety,” stating she needed to move from Texas due to Governor Abbott’s pronouncements there “to a state that won’t consider me an abuser when I seek medical care for my trans child and potentially remove her from my custody,” some parents feel the need instead to move from more liberal states.

Some tell their stories anonymously, as they don’t want to risk causing their gender-questioning children further distress, as detailed on the Genspect website.

A version of this article first appeared on Medscape.com.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

A version of this article first appeared on Medscape.com.

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

A version of this article first appeared on Medscape.com.

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

A version of this article first appeared on Medscape.com.

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.