From the Journals

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

Forty-five circulating proteins in plasma are linked to the risk for myocardial infarction (MI), showed a new study that confirms some known associations and identifies new ones. Several proteins are associated with MI in women but not men, and some proteins linked with MI in both men and women are more strongly associated with MI in women.

“We hope that our study will shed light on pathways in MI,” said principal author Olga Titova, PhD, an epidemiologist at Uppsala University in Uppsala, Sweden. The work was published in the European Heart Journal.

Martha Gulati, MD, a cardiologist and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles and coauthor of an accompanying editorial, said the novel discovery of different patterns between men and women makes this an exciting study. The findings “highlight that sex differences in disease phenotype begin at the molecular level,” she said.

Titova and her team analyzed thousands of patients in two databases — one in Sweden (11,751 patients), the other in the United Kingdom (51,613 patients) — to discover proteins in the patients who went on to have an MI. Using one database to discover biomarkers and a second to replicate the findings is a common approach, said Titova.

Casting a Wide Net to Catch Proteins

The two databases “make findings more generalizable, allow us to confirm robust associations, and help minimize the risk of false positives.” The two databases mean researchers are more confident that the findings can be applied across populations, Titova added.

A total of 44 proteins were associated with later MI in both databases, adjusted for common MI risk factors as well as such factors as education, diet, physical activity, and alcohol intake, Titova explained. An additional protein was included from the first database that was unavailable in the second. Some of the proteins have been found in other studies, and this study confirms the link. Others were new, and a few appear to protect patients from MI.

“Most of the proteins are related to or involved in inflammation and atherosclerosis,” said Titova.

This is the first study to cast such a wide net, Titova pointed out. While several proteins have previously been linked to MI, most earlier studies have focused on specific proteins in populations that already have coronary artery disease or have involved cohorts of men only.

But she stresses that this study poses more questions than it answers. More research is needed to determine how proteins are involved in pathways leading to MI. The study found that some proteins may be mediators of general cardiovascular disease risk, whereas others are involved in mechanisms specifically linked to MI. Many proteins are involved in atherosclerosis, thrombosis, inflammation, immune system–related pathways, injury and tissue repair, coagulation, bone homeostasis, and iron metabolism.

“At this point, some [proteins] appear to be causal, some seem to be an association,” said Titova. It remains to be determined “which are on the causal path, which are potential biomarkers, which are going to shed light on the mechanisms” of MI.

The study took a step toward determining which proteins might be involved in causing MI through an analysis of some protein levels determined by genetics. This found three proteins linked to a higher risk for MI and three linked to a lower risk.

It’s Different for Women

Thirteen of the proteins were linked with later MI in women, either exclusively or more strongly than in men. Many of these associations were replicated in the second database, showing an alignment across populations.

Titova said the reason for the sex difference remains a mystery. “We have to go to the molecular level. It could be a consequence of risk factors affecting the sexes differently or different biology” between men and women.

Gulati, who specializes in women’s heart health, explained, “We know inflammation is much more prevalent in women and is the pathway to cardiovascular disease.” She points out that noncardiac inflammatory diseases are also more prevalent in women. Other biomarkers for inflammation, such as C-reactive protein, are higher in women than in men. She thinks the underlying mechanisms could involve “how we [women] make our proteins and how we respond to hormones.”

By identifying proteins linked to MI in women, the study helps to fill an important gap in our knowledge. “I can’t tell you how many papers don’t even look at sex differences. If we don’t look, we won’t know there are differences,” Gulati said. “In much of our cardiac research, women are underrepresented.”

The findings of this trial and others like it may lead to new approaches to prevention and treatment, Titova and Gulati agreed. Several proteins found in this study that may have a causal link with MI are already targets of drug development, they added.

Titova said other proteins may be useful in the future as biomarkers that indicate a need for preventive action.

Gulati asked, “If we can show some of the proteins are involved in the inflammatory response — if they are causal and we can prevent them upfront — can we reduce the chance of MI?” She and Titova said the many questions remaining should prove a rewarding avenue for research.

A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

COVID-19 survivors show a more pronounced decline in kidney function than those who recover from pneumonia caused by other infections. This decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), is particularly steep among individuals who require hospitalization for COVID-19.

METHODOLOGY:

• SARS-CoV-2, the virus that causes COVID-19, has been associated with acute kidney injury, but its potential impact on long-term kidney function remains unclear.
• Researchers investigated the decline in kidney function after COVID-19 vs pneumonia by including all hospitalized and nonhospitalized adults from the Stockholm Creatinine Measurements Project who had at least one eGFR measurement in the 2 years before a positive COVID-19 test result or pneumonia diagnosis.
• Overall, 134,565 individuals (median age, 51 years; 55.6% women) who had their first SARS-CoV-2 infection between February 2020 and January 2022 were included, of whom 13.3% required hospitalization within 28 days of their first positive COVID-19 test result.
• They were compared with 35,987 patients (median age, 71 years; 53.8% women) who were diagnosed with pneumonia between February 2018 and January 2020; 46.5% of them required hospitalization.
• The primary outcome measure focused on the mean annual change in eGFR slopes before and after each infection; the secondary outcome assessed was the annual change in postinfection eGFR slopes between COVID-19 and pneumonia cases.

TAKEAWAY:

• Before COVID-19, eGFR changes were minimal, but after the infection, the average decline increased to 4.1 (95% CI, 3.8-4.4) mL/min/1.73 m²; however, in the pneumonia cohort, a decline in eGFR was noted both before and after the infection.
• After COVID-19, the mean annual decline in eGFR was 3.4% (95% CI, 3.2%-3.5%), increasing to 5.4% (95% CI, 5.2%-5.6%) for those who were hospitalized.
• In contrast, the pneumonia group experienced an average annual decline of 2.3% (95% CI, 2.1%-2.5%) after the infection, which remained unchanged when analyzing only patients who were hospitalized.
• The risk for a 25% reduction in eGFR was higher in patients with COVID-19 than in those with pneumonia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.34), with the risk being even higher among those who required hospitalization (HR, 1.42; 95% CI, 1.22-1.64).

IN PRACTICE:

“These findings help inform decisions regarding the need to monitor kidney function in survivors of COVID-19 and could have implications for policymakers regarding future healthcare planning and kidney service provision,” the authors wrote.

SOURCE:

This study was led by Viyaasan Mahalingasivam, MPhil, London School of Hygiene & Tropical Medicine, London, England. It was published online in JAMA Network Open.

LIMITATIONS:

This study lacked information on important confounders such as ethnicity and body mass index. The follow-up period was not long enough to fully evaluate the long-term association of COVID-19 with kidney function. Some individuals may have been misclassified as nonhospitalized if their first infection was mild and a subsequent infection required hospitalization.

DISCLOSURES:

This study was supported by grants from the National Institute for Health and Care Research, Njurfonden, Stig and Gunborg Westman Foundation, and the Swedish Research Council. One author reported receiving a Career Development Award from the National Institute for Health and Care Research, and another author reported receiving grants from Njurfonden, Stig and Gunborg Westman Foundation, Swedish Research Council, Swedish Heart Lung Foundation, and Region Stockholm during the conduct of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Doxycycline discharge kits significantly improve guideline-directed treatment and reduce time to definitive treatment in patients with chlamydia who were discharged from the emergency department (ED). 

METHODOLOGY:

• A single-center retrospective chart review included adults with positive chlamydia tests in the ED between 2021 and 2023.
• In total, 98 received doxycycline discharge kits; 72 patients were enrolled before the implementation of discharge kits for comparison.
• There were no differences in symptoms of infection between patients who received and those who did not receive the kit.
• Main outcome was the number of patients who received treatment.
• Secondary outcomes included 90-day return visits for complaints of sexually transmitted infections and time to treatment initiation.

TAKEAWAY:

• Appropriate treatment rates rose significantly post-implementation of the discharge kit (69.1% vs 45.8%; odds ratio, 2.63; P = .002).
• Implementation of the discharge kit also reduced the time to definitive treatment from 22.7 hours to 1.3 hours (P < .001).
• No significant differences in 90-day ED return visits, time to initial treatment in the ED, and doxycycline prescription via culture callback programs between the two groups.

IN PRACTICE:

“Pharmacy-driven doxycycline discharge kits significantly increased guideline-directed treatment and decreased time to treatment for chlamydia infections in the ED population at an urban academic medical center,” the authors wrote. “Overall, this initiative overcame barriers to treatment for a significant public health issue, supporting the need for expansion to other emergency departments across the country.”

SOURCE:

The study was led by Carly Loudermilk, Department of Pharmacy, Louisville, Kentucky, and was published online on November 14, 2024, in The American Journal of Emergency Medicine.

LIMITATIONS:

Retrospective design is the main limitation and lack of insurance fill history in some patients.

DISCLOSURES:

The study received no external funding. The authors disclosed no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

• The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
• They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
• They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

• L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
• The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
• Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
• Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized mortality rates for hepatocellular carcinoma (HCC) in the United States are expected to rise from 5.03 per 100,000 persons in 2022 to 6.39 per 100,000 persons by 2040. Alcohol-associated liver disease (ALD) will likely become the leading cause of HCC-related mortality by 2026, and metabolic dysfunction–associated steatotic liver disease (MASLD) is projected to become the second leading cause by 2032, a new analysis found. 

METHODOLOGY:

• HCC accounts for 75%-85% of primary liver cancers and most liver cancer deaths. Researchers have observed an upward trend in the incidence of and mortality from HCC in the past 2 decades.
• This cross-sectional study analyzed 188,280 HCC-related deaths among adults aged 25 and older to determine trends in mortality rates and project age-standardized mortality rates through 2040. Data came from the National Vital Statistics System database from 2006 to 2022.
• Researchers stratified mortality data by etiology of liver disease (ALD, hepatitis B virus, hepatitis C virus, and MASLD), age groups (25-64 or 65 and older years), sex, and race/ethnicity.
• Demographic data showed that 77.4% of deaths occurred in men, 55.6% in individuals aged 65 years or older, and 62.3% in White individuals.

TAKEAWAY:

• Overall, the age-standardized mortality rate for HCC-related deaths increased from 3.65 per 100,000 persons in 2006 to 5.03 in 2022 and was projected to increase to 6.39 per 100,000 persons by 2040.
• Sex- and age-related disparities were substantial. Men had much higher rates of HCC-related mortality than women (8.15 vs 2.33 per 100,000 persons), with a projected rate among men of 9.78 per 100,000 persons by 2040. HCC-related mortality rates for people aged 65 years or older were 10 times higher than for those aged 25-64 years (18.37 vs 1.79 per 100,000 persons) in 2022 and was projected to reach 32.81 per 100,000 persons by 2040 in the older group.
• Although hepatitis C virus–related deaths were projected to decline from 0.69 to 0.03 per 100,000 persons by 2034, ALD- and MASLD-related deaths showed increasing trends, with both projected to become the two leading causes of HCC-related mortality in the next few years.
• Racial disparities were also evident. By 2040, the American Indian/Alaska Native population showed the highest increase in projected HCC-related mortality rates, which went from 5.46 per 100,000 persons in 2006 to a project increase to 14.71 per 100,000 persons.

IN PRACTICE:

“HCC mortality was projected to continue increasing in the US, primarily due to rising rates of deaths attributable to ALD and MASLD,” the authors wrote. 

This “study highlights the importance of addressing these conditions to decrease the burden of liver disease and liver disease mortality in the future,” Emad Qayed, MD, MPH, Emory University School of Medicine, Atlanta, wrote in an accompanying editorial.

SOURCE:

The study was led by Sikai Qiu, MM, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and was published online in JAMA Network Open.
 

LIMITATIONS:

The National Vital Statistics System database used in this study captured only mortality data without access to detailed clinical records or individual medical histories. Researchers could not analyze socioeconomic factors or individual-level risk factors owing to data anonymization requirements. Additionally, the inclusion of the COVID-19 pandemic period could have influenced observed trends and reliability of future projections.
 

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China. Several authors reported receiving consulting fees, speaking fees, or research support from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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