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Latest steps toward reducing U.S. insulin cost begin in 2023
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
Gene associated with vision loss also linked to COVID: Study
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
FROM THE JOURNAL OF CLINICAL MEDICINE
Earlier colorectal cancer screening appears cost-effective in overweight, obese patients
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
‘Affect discrepancies’ may underlie negative symptoms in schizophrenia
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
IV ketamine a promising option for resistant depression in older adults
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
Treatment-resistant depression ups risk for comorbidities, death
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
FROM PSYCHIATRY
Physical activity eases depressive symptoms in young people
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
FROM JAMA PEDIATRICS
Five thoughts on the Damar Hamlin collapse
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
Exacerbation history found flawed as COPD risk predictor
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL CHEST
Small study finds high dose vitamin D relieved toxic erythema of chemotherapy
seen on an inpatient dermatology consultative service.
Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.
Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.
All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.
Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.
“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”
Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.
Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.
Dr. Nguyen and his coauthors reported no conflict of interest disclosures.
seen on an inpatient dermatology consultative service.
Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.
Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.
All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.
Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.
“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”
Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.
Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.
Dr. Nguyen and his coauthors reported no conflict of interest disclosures.
seen on an inpatient dermatology consultative service.
Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.
Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.
All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.
Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.
“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”
Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.
Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.
Dr. Nguyen and his coauthors reported no conflict of interest disclosures.
FROM JAMA DERMATOLOGY