Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Among a sample of younger women with invasive breast cancer and employer-sponsored insurance, outpatient-related out-of-pocket (OOP) costs were greater than drug costs.

For these same patients, prescriptions were largely for nonproprietary anticancer drugs and entailed limited OOP costs. For women with high-deductible health plans (HDHPs) and commercially driven health plans (CDHPs), OOP costs were higher, compared with coverage by more generous plans, according to the Research Letter published in JAMA Network Open.

“You would expect that people undergoing cancer treatment should not have to face very high out-of-pocket costs associated with care regardless of treatment modality because their treatment is largely guideline-indicated, and they have no choices,” stated corresponding author Rena Conti, PhD, associate professor with the school of business, Boston University, in an interview. “If you are diagnosed with cancer and undergoing treatment, you’re following the recommendation of your doctor, and your doctor is following standard protocols for treatment. In that scenario, Economics 101 suggests that people should not have to pay anything or [should pay] very little, especially for things that are cheap and are known to be effective, because there’s no overuse. Where normally we think that out-of-pocket costs are meant to control overuse, people with breast cancer are not opting to get more than indicated chemotherapy or radiation.”

The analysis of 25,224 women with invasive breast cancer diagnosis and claims for 1 or more of 14 oral anticancer drugs revealed that OOP costs for nondrug outpatient claims represented 79.0% of total costs. OOP drug costs were modest, with a 30-day supply ranging from $0.57-$0.60 for tamoxifen to $134.08-$141.07 for palbociclib.

“We were interested in understanding to what extent women who are insured with private insurance are exposed to out-of-pocket costs for standard breast cancer treatment, both in looking at drugs, but also the other aspects of the treatments they undergo.”

High OOP costs for the oral anticancer prescription drugs that are central to breast cancer treatment are associated with treatment nonadherence and discontinuation. Little has been known, however, about OOP costs of treatment associated with invasive breast cancer among employer-insured women younger than 65 years, the paper says.

“This population may face significant financial burdens related to long-term hormonal-based prevention and enrollment in high-deductible health plans and consumer-driven health plans,” the authors state in their paper.

In the cross-sectional study, which used the national 2018 Marative MarketScan database, 23.1% were HDHP- or CDHP-insured. Fifty-one percent had no OOP costs for drugs. The total mean estimated OOP cost, however, was $1,502.23 per patient, with inpatient costs representing only $112.41 (95% confidence interval, $112.40-$112.42); outpatient costs were $1,186.27 (95% CI, $1,185.67-$1,188.16). Pharmaceutical costs were $203.55 (95% CI, $203.34-$203.78).“We were surprised to find that the vast majority were getting breast cancer treatment with older, very effective, very safe, relatively inexpensive drugs and had limited out-of-pocket costs with some variation – higher costs for the few receiving newer, expensive drugs. The backbone of treatment is the older, generic drugs, which are cheap for both the insurers and the patients. But we found also that women are facing high out-of-pocket costs for nondrug-based therapy – specifically for doctor visits, getting check-ups, diagnostic scans, and maybe other types of treatment, as well. ... It’s a very different story than the one typically being told about the preponderance of out-of-pocket costs being drug-related,” Dr. Conti said.

The explanation may be that progress in breast cancer treatment over the last decades has led to effective treatments that are largely now inexpensive. The situation is different with ovarian cancer and many blood cancers such as chronic lymphocytic leukemia and multiple myeloma. For them, the new, innovative, safe, and effective drugs are very expensive, she noted.

“I think that insurers can modulate the out-of-pocket costs associated with drug treatment through formulary design and other tools they have. It’s less easy for them to modulate out-of-pocket costs associated with other modalties of care. Still, for medical care that is obviously necessary, there needs to be a cap on what women should have to pay,” Dr. Conti said.

A further concern raised by Dr. Conti is shrinking Medicaid coverage with the expiration of COVID-specific expanded Medicaid eligibility.

“Policy folks are closely watching the size of uninsured populations and also the growing importance of the high deductible and consumer-driven plans in which patients face high out-of-pocket first dollar coverage for care. With Medicaid rolls shrinking, we’ll see more people in low-premium, not well-insured plans. Americans’ exposure to higher costs for guideline-recommended care might grow, especially as more of them are independent contractors in the gig economy and not working for big corporations.”

“We worry that if and when they get a diagnosis of breast cancer, which is common among younger women, they are going to be faced with costs associated with their care that are going to have to be paid out-of-pocket – and it’s not going to be for the drug, it’s the other types of care. Doctors should know that the younger patient population that they are serving might be facing burdens associated with their care.”

Dr. Conti added, “Among women who are underinsured, there is a clear burden associated with cancer treatment. Reform efforts have largely focused on reducing out-of-pocket costs for seniors and have not focused much on guideline-consistent care for those under 65 who are working. Their burden can be quite onerous and cause financial harm for them and their families, resulting in worse health,” she continued, “Policy attention should go to unburdening people who have a serious diagnosis and who really have to be treated. There’s very good evidence that imposing additional out-of-pocket costs for guideline-consistent care causes people to make really hard decisions about paying rent versus paying for meds, about splitting pills and not doing all the things their physician is recommending, and about staying in jobs they don’t love but are locked into [because of health coverage].”

Dr. Conti concluded, “The good news is that, in breast cancer, the drugs work and are cheap. But the bad news is that there are many people who are underinsured and therefore, their care still has a high out-of-pocket burden. ACA radically changed working age people’s ability to qualify for insurance and be insured, but that didn’t mean that they are really well-covered when they become sick. They are still in peril over high out-of-pocket costs because of the proliferation of plans that are very skimpy. Women think they are insured until they get a diagnosis.”

Noting study limitations, Dr. Conti said that OOP costs cited are an underestimate, because many patients will also be treated for other comorbidities and complications related to treatment.

The authors disclosed no conflicts of interest. The study was funded by the American Cancer Society.

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

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

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

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

Implementing universal ultrasound during the third trimester of pregnancy significantly reduced the number of undiagnosed breech presentations, according to a study published in PLOS Medicine. The effects held if sonographers used a traditional ultrasound machine or if midwives used a handheld ultrasound tool to perform what is known as a point-of-care ultrasound (POCUS) procedure.

“Giving pregnant women a third-trimester scan reduces the rate of undetected breech in labor by over two-thirds, which reduces the chances of harm to the baby,” said Asma Khalil, MBBCh, MD, professor of obstetrics and maternal-fetal medicine at the University of London’s St. George’s Hospital, and a coauthor of the new study.

Routine ultrasounds typically are performed from the 10th to the 13th week of pregnancy, not during the third trimester, when the risk for a breech birth would be most apparent. Breech births occur in 3%-4% of pregnancies, raising the risk that babies will experience broken bones or hemorrhage. Knowing that breech is possible before birth enables physicians to discuss options with the pregnant woman in advance, Dr. Khalil said. These steps include rotating the baby in the uterus or conducting a cesarean delivery. Such counseling is not possible if breech is undetected until spontaneous or induced labor. 

“Breech presentation at term is not very common, but diagnosing it prior to the onset of labor or induction of labor offers patients much more flexibility in terms of options and planning,” said Cecilia B. Leggett, MD, a resident in obstetrics and gynecology at Cedars-Sinai in Los Angeles. Dr. Leggett, who was not involved in the study, has shown that handheld devices are as accurate at assessing fetal weight as are standard ultrasound machines.
 

Two tools, same result

Dr. Khalil and her colleagues compared the rates of undiagnosed breech presentations before and after implementing universal third-semester ultrasound at two hospitals in the United Kingdom. The requirement began in 2020; the study compared the rate of undiagnosed breeches from the period of 2016-2020 with that of 2020-2021.

St. George’s Hospital in London used a traditional ultrasound machine that is read by a sonographer, whereas the Norfolk and Norwich University Hospitals, in Norwich, England, employed midwives to use a handheld ultrasound device.

The rate of undiagnosed breech cases declined from 14.2% at St. George’s before the universal ultrasound requirement (82 missed cases of 578 breech births) to 2.8% after the requirement began (7 missed cases of 251 breech births). The story was similar at Norfolk and Norwich, where 16.2% missed breech cases occurred before the requirement (27 of 167) and 3.5% missed cases were reported after it (5 of 142).

The increased accuracy of breech diagnosis before labor probably led to fewer cases of impaired blood flow to a baby’s brain at birth, Dr. Khalil’s group reported, as well as a probable reduction in the number of stillborn babies or those who die extremely young.

Traditional ultrasound scans read by sonographers are expensive, Dr. Khalil noted, whereas the portable handheld devices are much cheaper and could be used widely to improve detection of breech births. That step would require robust training about how to properly use these devices, Dr. Leggett said.

“As we see more and more studies come out about technology for POCUS, I think it’s important to keep in mind that we need the education about the tools to be as accessible as the tools themselves,” she said.

Dr. Leggett had no relevant financial relationships. Dr. Khalil is a vice president of the Royal College of Obstetricians and Gynaecologists, is a trustee and the treasurer of the International Society of Ultrasound in Obstetrics and Gynecology, and has lectured at and consulted in several ultrasound-based projects, webinars, and educational events.
 

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

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

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

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

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

Three studies provide new insight into the growing problem of gaming disorder (GD), including the condition’s genesis, effective treatments, and the need for a greater focus on recovery.

A team of international researchers led by Orsolya Király, PhD, of the Institute of Psychology, Eötvös Loránd University, Budapest, reviewed the characteristics and etiology of GD. They concluded that its genesis arises from the interaction of environmental factors, game-specific factors and individual factors, including personality traits, comorbid psychopathology, and genetic predisposition.

“The development of GD is a complex process and we identified three major factors involved,” study coauthor Mark Griffiths, PhD, distinguished professor of behavioral addiction and director of the international gaming research unit, psychology department, Nottingham (England) Trent University, said in an interview. Because of this complexity, “prevention and intervention in GD require multiprofessional action.”

The review was published in Comprehensive Psychiatry.

In a second paper, published online in Frontiers in Psychiatry, Chinese investigators reviewing randomized controlled trials (RCTs) presented “compelling evidence” to support four effective interventions for GD: group counseling, acceptance and cognitive restructuring intervention program (ACRIP), short-term cognitive-behavioral therapy (CBT), and craving behavioral intervention (CBI).

A third paper, published online in the Journal of Behavioral Addictions, in which researchers analyzed close to 50 studies of GD, found that the concept of “recovery” is rarely mentioned in GD research. Lead author Belle Gavriel-Fried, PhD, senior professor, Bob Shapell School of Social Work, Tel Aviv University, said in an interview that recovery is a “holistic concept that taps into many aspects of life.”

Understanding the “differences in the impact and availability” of negative and positive human resources and their effect on recovery “can help clinicians to customize treatment,” she said.
 

Complex interplay

GD is garnering increasing attention in the clinical community, especially since 2019, when the World Health Organization included it in the ICD-11.

“Although for most individuals, gaming is a recreational activity or even a passion, a small group of gamers experiences negative symptoms which impact their mental and physical health and cause functional impairment,” wrote Dr. Király and colleagues.

Dr. Griffiths explained that his team wanted to provide an “up-to-date primer – a ‘one-stop shop’ – on all things etiologic concerning gaming disorder for academics and practitioners” as well as others, such as health policy makers, teachers, and individuals in the gaming industry.

The researchers identified three factors that increase the risk of developing GD, the first being gaming-related factors, which make video games “addictive in a way that vulnerable individuals may develop GD.”

For example, GD is more prevalent among online versus offline game players, possibly because online multiplayer games “provide safe environments in which players can fulfill their social needs while remaining invisible and anonymous.”

Game genre also matters, with massively multiplayer online role-playing games, first-person/third-person shooter games, real-time strategy games, and multiplayer online battle arena games most implicated in problematic gaming. Moreover, the “monetization techniques” of certain games also increase their addictive potential.

The researchers point to individual factors that increase the risk of developing GD, including male sex and younger age, personality traits like impulsivity and sensation-seeking, and comorbidities including ADHD, anxiety, and depression.

Poor self-esteem and lack of social competencies make gaming “an easy and efficient way to compensate for these deficiencies, which in turn, heightens the risk for developing GD,” they add. Neurobiological processes and genetic predisposition also play a role.

Lastly, the authors mentioned environmental factors, including family and peer-group issues, problems at work or school, and cultural factors.

“The take-home messages are that problematic gaming has had a long history of empirical research; that the psychiatric community now views GD as a legitimate mental health issue; and that the reasons for GD are complex, with many different factors involved in the acquisition, development, and maintenance of GD,” said Dr. Griffiths.
 

Beneficial behavioral therapies

Yuzhou Chen and colleagues, Southwest University, Chongqing, China, conducted a systematic review of RCTs investigating interventions for treating GD. Despite the “large number of intervention approaches developed over the past decade, as yet, there are no authoritative guidelines for what makes an effective GD intervention,” they wrote.

Few studies have focused specifically on GD but instead have focused on a combination of internet addiction and GD. But the interventions used to treat internet addiction may not apply to GD. And few studies have utilized an RCT design. The researchers therefore set out to review studies that specifically used an RCT design to investigate interventions for GD.

They searched six databases to identify RCTs that tested GD interventions from the inception of each database until the end of 2021. To be included, participants had to be diagnosed with GD and receive either a “complete and systematic intervention” or be in a comparator control group receiving no intervention or placebo.

Seven studies met the inclusion criteria (n = 332 participants). The studies tested five interventions:
 

• Group counseling with three different themes (interpersonal interaction, acceptance and commitment, cognition and behavior)
• CBI, which addresses cravings
• Transcranial direct current stimulation (tDCS)
• ACRIP with the main objectives of reducing GD symptoms and improving psychological well-being
• Short-term CBT, which addresses maladaptive cognitions

The mean duration of the interventions ranged from 3 to 15 weeks.

The primary outcome was GD severity, with secondary outcomes including depression, anxiety, cognition, game time, self-esteem, self-compassion, shyness, impulsivity, and psychological well-being.

Group counseling, CBI, ACRIP, and short-term CBT interventions had “a significant effect on decreasing the severity of GD,” while tDCS had “no significant effect.”

Behavioral therapy “exerts its effect on the behavioral mechanism of GD; for example, by reducing the association between game-related stimuli and the game player’s response to them,” the authors suggested.

Recovery vs. pathology

Recovery “traditionally represents the transition from trauma and illness to health,” Dr. Gavriel-Fried and colleagues noted.

Two paradigms of recovery are “deficit based” and “strength based.” The first assesses recovery in terms of abstinence, sobriety, and symptom reduction; and the second focuses on “growth, rather than a reduction in pathology.”

But although recovery is “embedded within mental health addiction policies and practice,” the concept has received “scant attention” in GD research.

The researchers therefore aimed to “map and summarize the state of the art on recovery from GD,” defining “recovery” as the “ability to handle conflicting feelings and emotions without external mediation.”

They conducted a scoping review of all literature regarding GD or internet GD published before February 2022 (47 studies, 2,924 participants with GD; mean age range, 13-26 years).

Most studies (n = 32) consisted of exclusively male subjects. Only 10 included both sexes, and female participants were in the minority.

Most studies (n = 42) did not address the concept of recovery, although all studies did report significant improvements in gaming-related pathology. Typical terminology used to describe changes in participants’ GD were “reduction” and/or “decrease” in symptom severity.

Although 18 studies mentioned the word “recovery,” only 5 actually discussed issues related to the notion of recovery, and only 5 used the term “abstinence.”

In addition, only 13 studies examined positive components of life in patients with GD, such as increased psychological well-being, life satisfaction, quality of life, improved emotional state, relational skills, and executive control, as well as improved self-care, hygiene, sleep, and interest in school studies.

“As a person and researcher who believes that words shape the way we perceive things, I think we should use the word ‘recovery’ rather than ‘pathology’ much more in research, therapy, and policy,” said Dr. Gavriel-Fried.

She noted that, because GD is a “relatively new behavioral addictive disorder, theories are still being developed and definitions of the symptoms are still being fine-tuned.”

“The field as a whole will benefit from future theoretical work that will lead to practical solutions for treating GD and ways to identify the risk factors,” Dr. Gavriel-Fried said.
 

Filling a research gap

In a comment, David Greenfield, MD, founder and medical director of the Connecticut-based Center for Internet and Technology Addiction, noted that 3 decades ago, there was almost no research into this area.

“The fact that we have these reviews and studies is good because all of the research adds to the science providing more data about an area we still don’t know that much about, where research is still in its infancy,” said Dr. Greenfield, who was not involved with the present study.

“Although we have definitions, there’s no complete agreement about the definitions of GD, and we do not yet have a unified approach,” continued Dr. Greenfield, who wrote the books Overcoming Internet Addiction for Dummies and Virtual Addiction.

He suggested that “recovery” is rarely used as a concept in GD research perhaps because there’s a “bifurcation in the field of addiction medicine in which behavioral addictions are not seen as equivalent to substance addictions,” and, particularly with GD, the principles of “recovery” have not yet matured.

“Recovery means meaningful life away from the screen, not just abstinence from the screen,” said Dr. Greenfield.

The study by Mr. Chen and colleagues was supported by grants from the National Social Science Foundation of China, the Chongqing Research Program of Basic Research and Frontier Technology, and the Fundamental Research Funds for the Central Universities. Dr. Griffiths has reported receiving research funding from Norsk Tipping (the gambling operator owned by the Norwegian government). The study by Dr. Király and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. The study by Dr. Gavriel-Fried and colleagues received support from the Hungarian National Research Development and Innovation Office and the Janos Bolyai Research Scholarship Academy of Sciences to individual investigators. Dr. Gavriel-Fried has reported receiving grants from the Israel National Insurance Institute and the Committee for Independent Studies of the Israel Lottery. Dr. Greenfield reported no relevant financial relationships.

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

The overnight shift in the MCU began as it does for many intensivists, by hearing about ED admissions, transfers from outside hospitals, sick floor patients, and high-risk patients in the MICU. Earlier in the day, the MICU team had admitted a 39-year-old woman with a severe asthma attack that required endotracheal intubation and mechanical ventilation in the ED for hypercarbic respiratory failure. After intubation, she had no audible air movement on chest exam, severe hypercarbic respiratory acidosis determined by an arterial blood gas, a clear chest radiograph, and negative findings on a respiratory viral panel. Her family said that she had run out of her steroid inhaler a month earlier and could not afford a refill. She had been using increasing amounts of albuterol over the past week before developing severe shortness of breath on the day of admission. The ED and MICU teams aggressively treated her with high-dose inhaled albuterol, ipratropium, and IV magnesium sulfate for bronchodilation; methylprednisolone for airway inflammation; and continuous ketamine for sedation, analgesia, and bronchodilation (Rehder KJ, et al. Respir Care. 2017;62[6]:849). Her airway pressures continued to be high despite using lung protective ventilation, so she was shifted to a permissive hypercapnia ventilation strategy using neuromuscular blockade, deep sedation, and low minute-ventilation (Laher AE, et al. J Intensive Care Med. 2018;33[9]:491).

CHEST

Two hours into the shift, the bedside nurse noted that the patient had become hypotensive. Her ventilator pressures remained stable with peak inspiratory pressures of 38-42 cm H₂O, plateau pressures of 28-30 cm H₂O, auto-positive end-expiratory pressure (auto-PEEP) of 10-12 cm H₂O, and fractional inspiratory oxygen (FiO₂) of 40%. A repeat chest radiograph showed no signs of barotrauma, but arterial blood gas values showed severe respiratory acidosis with a pH of 7.05 and a PCO₂ > 100 mm Hg. Her condition stabilized when she received a continuous infusion of bicarbonate to control her acidosis and low-dose IV norepinephrine for blood pressure control. It was at that moment that the bedside nurse astutely asked whether we should consider starting ECMO for the patient, as coauthor Dr. Arun Kannappan had done for a similar patient with asthma a month earlier. Dr. Vandivier notes, “My first response was that ECMO was not needed, because our patient had stabilized, and I had taken care of many patients like this in the past. But as I considered the situation more carefully, it was clear that any further decompensation could put our patient’s life at risk by not leaving enough time to start ECMO in a controlled setting. In short, my ‘traditional’ approach left little room for error in a patient with high ventilator pressures and hemodynamic instability.”

CHEST

ECMO is a technique used to add oxygen or remove CO₂ from the blood of people with different forms of respiratory failure (Fan E, et al. Intensive Care Med. 2016;2:712) that was first used by Hill and colleagues in 1966 for trauma-induced ARDS (Hill JD, et al. N Engl J Med. 1972;286:629). The ECMO circuit pumps blood from the venous system into an oxygenator that adds oxygen and removes CO₂ before blood is returned to either the venous or arterial circulation (Intensive Care Med. 2016;42:712). Venovenous ECMO (vvECMO) is used in clinical scenarios where only oxygenation and/or CO₂ removal is needed, whereas venoarterial ECMO (vaECMO) is reserved for situations where additional hemodynamic support is necessary. ECMO is traditionally thought of as a means to increase blood oxygenation, but it is less widely appreciated that ECMO is particularly effective at removing blood CO₂. In addition to ECMO helping to normalize oxygenation or eliminate CO₂, it can also be used to lower tidal volumes, decrease airway pressures, and allow “lungs to rest” with the goal of avoiding ventilator-induced lung injury (VILI).

CHEST

Standing at the bedside, it seemed to the authors that it was the right time to think about instituting a salvage therapy. But was there evidence that ECMO could improve survival? Were there clear guidelines for when to initiate ECMO, and was ECMO more effective than other salvage therapies such as inhaled volatile anesthetics?

Since McDonnell and colleagues first described the use of ECMO for a severe asthma exacerbation in 1981 (Ann Thoracic Surg. 1981;31[2]:171), about 95 articles have been published. Other than two registry studies and a recent epidemiologic study, all of these publications were case reports, case series, and reviews. Mikkelsen and colleagues (ASAIO J. 2009;55[1]:47) performed a retrospective, cohort study using the International Extracorporeal Life Support (ECLS) Organization Registry to determine whether ECMO use for status asthmaticus was associated with greater survival than the use of ECMO for other causes of respiratory failure. From 1986 through 2006, a total of 2,127 cases of respiratory failure were identified that required ECMO, including 27 for status asthmaticus and 1,233 for other causes. Their analysis showed that 83.3% of asthmatics treated with ECMO survived to hospital discharge, compared with 50.8% of people treated with ECMO for respiratory failure not due to asthma, with an odds ratio (OR) of 4.86 favoring survival of asthmatics (OR = 4.86; 95% CI, 1.65-14.31, P = .004).

Yeo and colleagues (Yeo HJ, et al. Critical Care. 2017;21:297) also used the ECLS Organization Registry to measure survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality for asthmatics treated with ECMO. They included 272 people treated with ECMO for asthma between 1992 and 2016, after excluding people treated with ECMO for cardiopulmonary resuscitation or cardiac dysfunction. ECMO was associated with improvements in ventilator mechanics, including a reduction in respiratory rate, FiO₂, peak inspiratory pressure, mean airway pressure, and driving pressure. Use of ECMO for status asthmaticus was also associated with an 83.5% survival to hospital discharge, similar to the study by Mikkelsen and colleagues. Hemorrhage, the most common complication, occurred in roughly a quarter of people treated with ECMO. In the multivariate analysis, age, bleeding, pre-ECMO PEEP, post-ECMO FiO₂, and driving pressure were all associated with higher in-hospital mortality.

Although there are no formal criteria to guide use of ECMO for asthma exacerbations with respiratory failure, a number of physicians and a physician organization have recommended that ECMO be considered for persistently high ventilator pressures, uncontrolled respiratory acidosis, or hemodynamic instability. Because our patient qualified for ECMO based on all three suggested criteria, we consulted cardiac surgery who quickly started her on vvECMO. She remained on ECMO for 4 days until she was decannulated, extubated, and discharged home.

Despite this positive outcome, the lack of a high-quality, controlled study to help guide our decision was surprising given the ability of ECMO to efficiently remove CO₂ and to decrease ventilator pressures. The lack of guidance prompted us to perform a retrospective, epidemiologic cohort study to determine whether treatment with ECMO for asthma exacerbations with respiratory failure was associated with reduced mortality, compared with people treated without ECMO (Zakrajsek JK, Chest. 2023;163[1]:38). The study included 13,714 people admitted to an ECMO-capable hospital with respiratory failure that required invasive ventilation because of an asthma exacerbation between 2010 and 2020, of which 127 were treated with ECMO and 13,587 were not. During this period, use of ECMO as a salvage therapy for severe asthma exacerbations was a rare event, but it became more common over time. With the limitation that 40% of asthma patients were transferred from an outside hospital, 74% were started on ECMO in the first 2 hospital days, and 94% were started within the first week of hospitalization. Once started, ECMO was continued for a median of 1.0 day and range of 1-49 days. Hospital mortality was 14.6% in the ECMO group versus 26.2% in the no ECMO group, which equated to an 11.6% absolute risk reduction (P = 0.03) and 52% relative risk reduction (P = 0.04) in mortality. ECMO was associated with hospital costs that were $114,000 higher per patient, compared with the no ECMO group, but did not affect intensive care unit length of stay, hospital length of stay, or time on invasive mechanical ventilation.

We were pleased that our patient had a good outcome, and were reassured by our study results. But we were left to wonder whether ECMO really was the best salvage therapy for asthma exacerbations with respiratory failure, and if it was initiated for the right indications at the best time. These are important treatment considerations that take on new urgency given that physicians are increasingly looking to ECMO as a salvage therapy for refractory asthma, and the recent FDA approval of low-flow, extracorporeal CO₂ removal systems that could make CO₂ removal a more available, and perhaps less expensive, strategy. Despite promising epidemiological data, it will be important that these questions are answered with well-designed clinical trials so that physicians can be armed with the knowledge needed to navigate complex clinical scenarios, and ultimately to prevent unfortunate deaths from a reversible disease.

The overnight shift in the MCU began as it does for many intensivists, by hearing about ED admissions, transfers from outside hospitals, sick floor patients, and high-risk patients in the MICU. Earlier in the day, the MICU team had admitted a 39-year-old woman with a severe asthma attack that required endotracheal intubation and mechanical ventilation in the ED for hypercarbic respiratory failure. After intubation, she had no audible air movement on chest exam, severe hypercarbic respiratory acidosis determined by an arterial blood gas, a clear chest radiograph, and negative findings on a respiratory viral panel. Her family said that she had run out of her steroid inhaler a month earlier and could not afford a refill. She had been using increasing amounts of albuterol over the past week before developing severe shortness of breath on the day of admission. The ED and MICU teams aggressively treated her with high-dose inhaled albuterol, ipratropium, and IV magnesium sulfate for bronchodilation; methylprednisolone for airway inflammation; and continuous ketamine for sedation, analgesia, and bronchodilation (Rehder KJ, et al. Respir Care. 2017;62[6]:849). Her airway pressures continued to be high despite using lung protective ventilation, so she was shifted to a permissive hypercapnia ventilation strategy using neuromuscular blockade, deep sedation, and low minute-ventilation (Laher AE, et al. J Intensive Care Med. 2018;33[9]:491).

CHEST

Two hours into the shift, the bedside nurse noted that the patient had become hypotensive. Her ventilator pressures remained stable with peak inspiratory pressures of 38-42 cm H₂O, plateau pressures of 28-30 cm H₂O, auto-positive end-expiratory pressure (auto-PEEP) of 10-12 cm H₂O, and fractional inspiratory oxygen (FiO₂) of 40%. A repeat chest radiograph showed no signs of barotrauma, but arterial blood gas values showed severe respiratory acidosis with a pH of 7.05 and a PCO₂ > 100 mm Hg. Her condition stabilized when she received a continuous infusion of bicarbonate to control her acidosis and low-dose IV norepinephrine for blood pressure control. It was at that moment that the bedside nurse astutely asked whether we should consider starting ECMO for the patient, as coauthor Dr. Arun Kannappan had done for a similar patient with asthma a month earlier. Dr. Vandivier notes, “My first response was that ECMO was not needed, because our patient had stabilized, and I had taken care of many patients like this in the past. But as I considered the situation more carefully, it was clear that any further decompensation could put our patient’s life at risk by not leaving enough time to start ECMO in a controlled setting. In short, my ‘traditional’ approach left little room for error in a patient with high ventilator pressures and hemodynamic instability.”

CHEST

ECMO is a technique used to add oxygen or remove CO₂ from the blood of people with different forms of respiratory failure (Fan E, et al. Intensive Care Med. 2016;2:712) that was first used by Hill and colleagues in 1966 for trauma-induced ARDS (Hill JD, et al. N Engl J Med. 1972;286:629). The ECMO circuit pumps blood from the venous system into an oxygenator that adds oxygen and removes CO₂ before blood is returned to either the venous or arterial circulation (Intensive Care Med. 2016;42:712). Venovenous ECMO (vvECMO) is used in clinical scenarios where only oxygenation and/or CO₂ removal is needed, whereas venoarterial ECMO (vaECMO) is reserved for situations where additional hemodynamic support is necessary. ECMO is traditionally thought of as a means to increase blood oxygenation, but it is less widely appreciated that ECMO is particularly effective at removing blood CO₂. In addition to ECMO helping to normalize oxygenation or eliminate CO₂, it can also be used to lower tidal volumes, decrease airway pressures, and allow “lungs to rest” with the goal of avoiding ventilator-induced lung injury (VILI).

CHEST

Standing at the bedside, it seemed to the authors that it was the right time to think about instituting a salvage therapy. But was there evidence that ECMO could improve survival? Were there clear guidelines for when to initiate ECMO, and was ECMO more effective than other salvage therapies such as inhaled volatile anesthetics?

Since McDonnell and colleagues first described the use of ECMO for a severe asthma exacerbation in 1981 (Ann Thoracic Surg. 1981;31[2]:171), about 95 articles have been published. Other than two registry studies and a recent epidemiologic study, all of these publications were case reports, case series, and reviews. Mikkelsen and colleagues (ASAIO J. 2009;55[1]:47) performed a retrospective, cohort study using the International Extracorporeal Life Support (ECLS) Organization Registry to determine whether ECMO use for status asthmaticus was associated with greater survival than the use of ECMO for other causes of respiratory failure. From 1986 through 2006, a total of 2,127 cases of respiratory failure were identified that required ECMO, including 27 for status asthmaticus and 1,233 for other causes. Their analysis showed that 83.3% of asthmatics treated with ECMO survived to hospital discharge, compared with 50.8% of people treated with ECMO for respiratory failure not due to asthma, with an odds ratio (OR) of 4.86 favoring survival of asthmatics (OR = 4.86; 95% CI, 1.65-14.31, P = .004).

Yeo and colleagues (Yeo HJ, et al. Critical Care. 2017;21:297) also used the ECLS Organization Registry to measure survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality for asthmatics treated with ECMO. They included 272 people treated with ECMO for asthma between 1992 and 2016, after excluding people treated with ECMO for cardiopulmonary resuscitation or cardiac dysfunction. ECMO was associated with improvements in ventilator mechanics, including a reduction in respiratory rate, FiO₂, peak inspiratory pressure, mean airway pressure, and driving pressure. Use of ECMO for status asthmaticus was also associated with an 83.5% survival to hospital discharge, similar to the study by Mikkelsen and colleagues. Hemorrhage, the most common complication, occurred in roughly a quarter of people treated with ECMO. In the multivariate analysis, age, bleeding, pre-ECMO PEEP, post-ECMO FiO₂, and driving pressure were all associated with higher in-hospital mortality.

Although there are no formal criteria to guide use of ECMO for asthma exacerbations with respiratory failure, a number of physicians and a physician organization have recommended that ECMO be considered for persistently high ventilator pressures, uncontrolled respiratory acidosis, or hemodynamic instability. Because our patient qualified for ECMO based on all three suggested criteria, we consulted cardiac surgery who quickly started her on vvECMO. She remained on ECMO for 4 days until she was decannulated, extubated, and discharged home.

Despite this positive outcome, the lack of a high-quality, controlled study to help guide our decision was surprising given the ability of ECMO to efficiently remove CO₂ and to decrease ventilator pressures. The lack of guidance prompted us to perform a retrospective, epidemiologic cohort study to determine whether treatment with ECMO for asthma exacerbations with respiratory failure was associated with reduced mortality, compared with people treated without ECMO (Zakrajsek JK, Chest. 2023;163[1]:38). The study included 13,714 people admitted to an ECMO-capable hospital with respiratory failure that required invasive ventilation because of an asthma exacerbation between 2010 and 2020, of which 127 were treated with ECMO and 13,587 were not. During this period, use of ECMO as a salvage therapy for severe asthma exacerbations was a rare event, but it became more common over time. With the limitation that 40% of asthma patients were transferred from an outside hospital, 74% were started on ECMO in the first 2 hospital days, and 94% were started within the first week of hospitalization. Once started, ECMO was continued for a median of 1.0 day and range of 1-49 days. Hospital mortality was 14.6% in the ECMO group versus 26.2% in the no ECMO group, which equated to an 11.6% absolute risk reduction (P = 0.03) and 52% relative risk reduction (P = 0.04) in mortality. ECMO was associated with hospital costs that were $114,000 higher per patient, compared with the no ECMO group, but did not affect intensive care unit length of stay, hospital length of stay, or time on invasive mechanical ventilation.

We were pleased that our patient had a good outcome, and were reassured by our study results. But we were left to wonder whether ECMO really was the best salvage therapy for asthma exacerbations with respiratory failure, and if it was initiated for the right indications at the best time. These are important treatment considerations that take on new urgency given that physicians are increasingly looking to ECMO as a salvage therapy for refractory asthma, and the recent FDA approval of low-flow, extracorporeal CO₂ removal systems that could make CO₂ removal a more available, and perhaps less expensive, strategy. Despite promising epidemiological data, it will be important that these questions are answered with well-designed clinical trials so that physicians can be armed with the knowledge needed to navigate complex clinical scenarios, and ultimately to prevent unfortunate deaths from a reversible disease.

The overnight shift in the MCU began as it does for many intensivists, by hearing about ED admissions, transfers from outside hospitals, sick floor patients, and high-risk patients in the MICU. Earlier in the day, the MICU team had admitted a 39-year-old woman with a severe asthma attack that required endotracheal intubation and mechanical ventilation in the ED for hypercarbic respiratory failure. After intubation, she had no audible air movement on chest exam, severe hypercarbic respiratory acidosis determined by an arterial blood gas, a clear chest radiograph, and negative findings on a respiratory viral panel. Her family said that she had run out of her steroid inhaler a month earlier and could not afford a refill. She had been using increasing amounts of albuterol over the past week before developing severe shortness of breath on the day of admission. The ED and MICU teams aggressively treated her with high-dose inhaled albuterol, ipratropium, and IV magnesium sulfate for bronchodilation; methylprednisolone for airway inflammation; and continuous ketamine for sedation, analgesia, and bronchodilation (Rehder KJ, et al. Respir Care. 2017;62[6]:849). Her airway pressures continued to be high despite using lung protective ventilation, so she was shifted to a permissive hypercapnia ventilation strategy using neuromuscular blockade, deep sedation, and low minute-ventilation (Laher AE, et al. J Intensive Care Med. 2018;33[9]:491).

CHEST

Two hours into the shift, the bedside nurse noted that the patient had become hypotensive. Her ventilator pressures remained stable with peak inspiratory pressures of 38-42 cm H₂O, plateau pressures of 28-30 cm H₂O, auto-positive end-expiratory pressure (auto-PEEP) of 10-12 cm H₂O, and fractional inspiratory oxygen (FiO₂) of 40%. A repeat chest radiograph showed no signs of barotrauma, but arterial blood gas values showed severe respiratory acidosis with a pH of 7.05 and a PCO₂ > 100 mm Hg. Her condition stabilized when she received a continuous infusion of bicarbonate to control her acidosis and low-dose IV norepinephrine for blood pressure control. It was at that moment that the bedside nurse astutely asked whether we should consider starting ECMO for the patient, as coauthor Dr. Arun Kannappan had done for a similar patient with asthma a month earlier. Dr. Vandivier notes, “My first response was that ECMO was not needed, because our patient had stabilized, and I had taken care of many patients like this in the past. But as I considered the situation more carefully, it was clear that any further decompensation could put our patient’s life at risk by not leaving enough time to start ECMO in a controlled setting. In short, my ‘traditional’ approach left little room for error in a patient with high ventilator pressures and hemodynamic instability.”

CHEST

ECMO is a technique used to add oxygen or remove CO₂ from the blood of people with different forms of respiratory failure (Fan E, et al. Intensive Care Med. 2016;2:712) that was first used by Hill and colleagues in 1966 for trauma-induced ARDS (Hill JD, et al. N Engl J Med. 1972;286:629). The ECMO circuit pumps blood from the venous system into an oxygenator that adds oxygen and removes CO₂ before blood is returned to either the venous or arterial circulation (Intensive Care Med. 2016;42:712). Venovenous ECMO (vvECMO) is used in clinical scenarios where only oxygenation and/or CO₂ removal is needed, whereas venoarterial ECMO (vaECMO) is reserved for situations where additional hemodynamic support is necessary. ECMO is traditionally thought of as a means to increase blood oxygenation, but it is less widely appreciated that ECMO is particularly effective at removing blood CO₂. In addition to ECMO helping to normalize oxygenation or eliminate CO₂, it can also be used to lower tidal volumes, decrease airway pressures, and allow “lungs to rest” with the goal of avoiding ventilator-induced lung injury (VILI).

CHEST

Standing at the bedside, it seemed to the authors that it was the right time to think about instituting a salvage therapy. But was there evidence that ECMO could improve survival? Were there clear guidelines for when to initiate ECMO, and was ECMO more effective than other salvage therapies such as inhaled volatile anesthetics?

Since McDonnell and colleagues first described the use of ECMO for a severe asthma exacerbation in 1981 (Ann Thoracic Surg. 1981;31[2]:171), about 95 articles have been published. Other than two registry studies and a recent epidemiologic study, all of these publications were case reports, case series, and reviews. Mikkelsen and colleagues (ASAIO J. 2009;55[1]:47) performed a retrospective, cohort study using the International Extracorporeal Life Support (ECLS) Organization Registry to determine whether ECMO use for status asthmaticus was associated with greater survival than the use of ECMO for other causes of respiratory failure. From 1986 through 2006, a total of 2,127 cases of respiratory failure were identified that required ECMO, including 27 for status asthmaticus and 1,233 for other causes. Their analysis showed that 83.3% of asthmatics treated with ECMO survived to hospital discharge, compared with 50.8% of people treated with ECMO for respiratory failure not due to asthma, with an odds ratio (OR) of 4.86 favoring survival of asthmatics (OR = 4.86; 95% CI, 1.65-14.31, P = .004).

Yeo and colleagues (Yeo HJ, et al. Critical Care. 2017;21:297) also used the ECLS Organization Registry to measure survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality for asthmatics treated with ECMO. They included 272 people treated with ECMO for asthma between 1992 and 2016, after excluding people treated with ECMO for cardiopulmonary resuscitation or cardiac dysfunction. ECMO was associated with improvements in ventilator mechanics, including a reduction in respiratory rate, FiO₂, peak inspiratory pressure, mean airway pressure, and driving pressure. Use of ECMO for status asthmaticus was also associated with an 83.5% survival to hospital discharge, similar to the study by Mikkelsen and colleagues. Hemorrhage, the most common complication, occurred in roughly a quarter of people treated with ECMO. In the multivariate analysis, age, bleeding, pre-ECMO PEEP, post-ECMO FiO₂, and driving pressure were all associated with higher in-hospital mortality.

Although there are no formal criteria to guide use of ECMO for asthma exacerbations with respiratory failure, a number of physicians and a physician organization have recommended that ECMO be considered for persistently high ventilator pressures, uncontrolled respiratory acidosis, or hemodynamic instability. Because our patient qualified for ECMO based on all three suggested criteria, we consulted cardiac surgery who quickly started her on vvECMO. She remained on ECMO for 4 days until she was decannulated, extubated, and discharged home.

Despite this positive outcome, the lack of a high-quality, controlled study to help guide our decision was surprising given the ability of ECMO to efficiently remove CO₂ and to decrease ventilator pressures. The lack of guidance prompted us to perform a retrospective, epidemiologic cohort study to determine whether treatment with ECMO for asthma exacerbations with respiratory failure was associated with reduced mortality, compared with people treated without ECMO (Zakrajsek JK, Chest. 2023;163[1]:38). The study included 13,714 people admitted to an ECMO-capable hospital with respiratory failure that required invasive ventilation because of an asthma exacerbation between 2010 and 2020, of which 127 were treated with ECMO and 13,587 were not. During this period, use of ECMO as a salvage therapy for severe asthma exacerbations was a rare event, but it became more common over time. With the limitation that 40% of asthma patients were transferred from an outside hospital, 74% were started on ECMO in the first 2 hospital days, and 94% were started within the first week of hospitalization. Once started, ECMO was continued for a median of 1.0 day and range of 1-49 days. Hospital mortality was 14.6% in the ECMO group versus 26.2% in the no ECMO group, which equated to an 11.6% absolute risk reduction (P = 0.03) and 52% relative risk reduction (P = 0.04) in mortality. ECMO was associated with hospital costs that were $114,000 higher per patient, compared with the no ECMO group, but did not affect intensive care unit length of stay, hospital length of stay, or time on invasive mechanical ventilation.

We were pleased that our patient had a good outcome, and were reassured by our study results. But we were left to wonder whether ECMO really was the best salvage therapy for asthma exacerbations with respiratory failure, and if it was initiated for the right indications at the best time. These are important treatment considerations that take on new urgency given that physicians are increasingly looking to ECMO as a salvage therapy for refractory asthma, and the recent FDA approval of low-flow, extracorporeal CO₂ removal systems that could make CO₂ removal a more available, and perhaps less expensive, strategy. Despite promising epidemiological data, it will be important that these questions are answered with well-designed clinical trials so that physicians can be armed with the knowledge needed to navigate complex clinical scenarios, and ultimately to prevent unfortunate deaths from a reversible disease.

Airways Disorders Network

Asthma & COPD Section

The 2023 GOLD committee proposed changes in nomenclature and therapy for various subgroups of patients with COPD. The 2023 GOLD committee changed the ABCD group classification to ABE (for exacerbations), which highlights the importance of the number and severity of exacerbations irrespective of daily symptoms.

The mainstay of initial treatment for symptomatic COPD should include combination LABA/LAMA bronchodilators in a single inhaler. For patients with features of concomitant asthma or eosinophils greater than or equal to 300 cells/microliter, an ICS/LABA/LAMA combination inhaler is recommended.

People with “young COPD” develop respiratory symptoms and meet spirometric criteria for COPD between the ages of 25 and 50 years old. Other terminology changes center around those with functional and/or structural changes suggesting COPD, but who do not meet the postbronchodilator spirometric criteria to confirm the COPD diagnosis.

Those with “pre-COPD” have normal spirometry, including the FEV₁ and FEV₁/FVC ratio, but have functional and/or structural changes concerning for COPD. Functional changes include air trapping and/or hyperinflation on PFTs, low diffusion capacity, and/or decline in FEV₁ of > 40 mL per year.

Structural changes include emphysematous changes and/or bronchial wall changes on CT scans. “PRISm” stands for preserved ratio with impaired spirometry, where the postbronchodilator FEV₁/FVC is greater than or equal to 0.70, but FEV₁ is < 80% predicted with similar functional and/or structural changes to those with “pre-COPD.” People with PRISm have increased all-cause mortality. Not all people with pre-COPD or PRISm progress clinically and spirometrically to COPD; however, they should be treated because they have symptoms as well as functional and/or structural abnormalities. Despite increasing data regarding pre-COPD and PRISm, many gaps remain regarding optimal management.

Maria Ashar, MD, MBBS
Section Fellow-in-Training

Max J. Martin, MD
Section Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Section Member-at-Large

Airways Disorders Network

Asthma & COPD Section

The 2023 GOLD committee proposed changes in nomenclature and therapy for various subgroups of patients with COPD. The 2023 GOLD committee changed the ABCD group classification to ABE (for exacerbations), which highlights the importance of the number and severity of exacerbations irrespective of daily symptoms.

The mainstay of initial treatment for symptomatic COPD should include combination LABA/LAMA bronchodilators in a single inhaler. For patients with features of concomitant asthma or eosinophils greater than or equal to 300 cells/microliter, an ICS/LABA/LAMA combination inhaler is recommended.

People with “young COPD” develop respiratory symptoms and meet spirometric criteria for COPD between the ages of 25 and 50 years old. Other terminology changes center around those with functional and/or structural changes suggesting COPD, but who do not meet the postbronchodilator spirometric criteria to confirm the COPD diagnosis.

Those with “pre-COPD” have normal spirometry, including the FEV₁ and FEV₁/FVC ratio, but have functional and/or structural changes concerning for COPD. Functional changes include air trapping and/or hyperinflation on PFTs, low diffusion capacity, and/or decline in FEV₁ of > 40 mL per year.

Structural changes include emphysematous changes and/or bronchial wall changes on CT scans. “PRISm” stands for preserved ratio with impaired spirometry, where the postbronchodilator FEV₁/FVC is greater than or equal to 0.70, but FEV₁ is < 80% predicted with similar functional and/or structural changes to those with “pre-COPD.” People with PRISm have increased all-cause mortality. Not all people with pre-COPD or PRISm progress clinically and spirometrically to COPD; however, they should be treated because they have symptoms as well as functional and/or structural abnormalities. Despite increasing data regarding pre-COPD and PRISm, many gaps remain regarding optimal management.

Maria Ashar, MD, MBBS
Section Fellow-in-Training

Max J. Martin, MD
Section Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Section Member-at-Large

Airways Disorders Network

Asthma & COPD Section

The 2023 GOLD committee proposed changes in nomenclature and therapy for various subgroups of patients with COPD. The 2023 GOLD committee changed the ABCD group classification to ABE (for exacerbations), which highlights the importance of the number and severity of exacerbations irrespective of daily symptoms.

The mainstay of initial treatment for symptomatic COPD should include combination LABA/LAMA bronchodilators in a single inhaler. For patients with features of concomitant asthma or eosinophils greater than or equal to 300 cells/microliter, an ICS/LABA/LAMA combination inhaler is recommended.

People with “young COPD” develop respiratory symptoms and meet spirometric criteria for COPD between the ages of 25 and 50 years old. Other terminology changes center around those with functional and/or structural changes suggesting COPD, but who do not meet the postbronchodilator spirometric criteria to confirm the COPD diagnosis.

Those with “pre-COPD” have normal spirometry, including the FEV₁ and FEV₁/FVC ratio, but have functional and/or structural changes concerning for COPD. Functional changes include air trapping and/or hyperinflation on PFTs, low diffusion capacity, and/or decline in FEV₁ of > 40 mL per year.

Structural changes include emphysematous changes and/or bronchial wall changes on CT scans. “PRISm” stands for preserved ratio with impaired spirometry, where the postbronchodilator FEV₁/FVC is greater than or equal to 0.70, but FEV₁ is < 80% predicted with similar functional and/or structural changes to those with “pre-COPD.” People with PRISm have increased all-cause mortality. Not all people with pre-COPD or PRISm progress clinically and spirometrically to COPD; however, they should be treated because they have symptoms as well as functional and/or structural abnormalities. Despite increasing data regarding pre-COPD and PRISm, many gaps remain regarding optimal management.

Maria Ashar, MD, MBBS
Section Fellow-in-Training

Max J. Martin, MD
Section Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Section Member-at-Large