Carolyn Crist

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A multicomponent exercise program that includes strength, aerobic, agility, and balance training exercises is cost-effective and results in improved cognition among stroke survivors, compared with a balance and tone control group, according to a new analysis.

On the other hand, a program consisting of cognitive and social enrichment activities that includes memory, brain training, and group social games entailed higher costs, compared with the balance and tone group, which included stretches, deep breathing and relaxation techniques, posture education, and core control exercises.

“Cognitive impairment is experienced in approximately one-third of stroke survivors,” study author Jennifer Davis, PhD, a Canada research chair in applied health economics and assistant professor of management at the University of British Columbia in Kelowna, said in an interview.

“The economic evaluation of the exercise intervention demonstrated that the multicomponent exercise program provided good value for the money when comparing costs and cognitive outcomes,” she said. However, “impacts on health-related quality of life were not observed.”

The study was published online November 30 in JAMA Network Open. 
 

Comparing Three Approaches

Despite improved care, patients with stroke often face challenges with physical function, cognitive abilities, and quality of life, the authors wrote. Among older adults, in particular, cognitive deficits remain prevalent and are associated with increased risks for dementia, mortality, and increased burdens for patients, caregivers, and health systems.

Numerous interventions have shown promise for post-stroke cognitive rehabilitation, including exercise and cognitive training, the authors wrote. Research hasn’t indicated which programs offer the most efficient or cost-effective options, however.

Dr. Davis and colleagues conducted an economic evaluation alongside the Vitality study, a three-group randomized clinical trial that examined the efficacy of improving cognitive function among patients with chronic stroke through a multicomponent exercise program, cognitive and social enrichment activities, or a control group with balance and tone activities. 

The economic evaluation team included a cost-effectiveness analysis (based on incremental cost per cognitive function change) and a cost-utility analysis (incremental cost per quality-adjusted life-year [QALY] gained). The researchers used a cost-effectiveness threshold of CAD $50,000 (Canadian dollars) per QALY for the cost-utility analysis, which was based on precedent treatment in Canada.

The clinical trial included 120 community-dwelling adults aged 55 years and older who had a stroke at least 12 months before the study. Based in the Vancouver metropolitan area, participants were randomly assigned to twice-weekly, 60-minute classes led by trained instructors for 26 weeks. The mean age was 71 years, and 62% of participants were men.

Exercise Effective

Overall, the balance and tone control group had the lowest delivery cost at CAD $777 per person, followed by CAD $1090 per person for the exercise group and CAD $1492 per person for the cognitive and social enrichment group.

After the 6-month intervention, the mean cognitive scores were –0.192 for the exercise group, –0.184 for the cognitive and social enrichment group, and –0.171 for the balance and tone group, indicating better cognitive function across all three groups.

In the cost-effectiveness analysis, the exercise intervention was costlier but more effective than the control group, with an incremental cost-effectiveness ratio (ICER) of CAD –$8823.

In the cost-utility analysis, the exercise intervention was cost saving (less costly and more effective), compared with the control group, with an ICER of CAD –$3381 per QALY gained at the end of the intervention and an ICER of CAD –$154,198 per QALY gained at the end of the 12-month follow-up period. The cognitive and social enrichment program was more costly and more effective than the control group, with an ICER of CAD $101,687 per QALY gained at the end of the intervention and an ICER of CAD $331,306 per QALY gained at the end of the follow-up period.

In additional analyses, the exercise group had the lowest healthcare resource utilization due to lower healthcare costs for physician visits and lab tests.

“This study provides initial data that suggests multicomponent exercise may be a cost-effective solution for combating cognitive decline among stroke survivors,” said Dr. Davis.

Overall, exercise was cost-effective for improving cognitive function but not quality of life among participants. The clinical trial was powered to detect changes in cognitive function rather than quality of life, so it lacked statistical power to detect differences in quality of life, said Dr. Davis.

Exercise programs and cognitive and social enrichment programs show promise for improving cognitive function after stroke, the authors wrote, though future research should focus on optimizing cost-effectiveness and enhancing health-related quality of life.

Considering Additional Benefits

Commenting on the study, Alan Tam, MD, a physiatrist at the Toronto Rehabilitation Institute’s Brain Rehabilitation Program, said, “The authors show that within the timeframe of their analysis, there is a trend to cost-effectiveness for the cognitive intervention being offered.” Dr. Tam did not participate in the research.

“However, the finding is not robust, as less than 50% of their simulations would meet their acceptability level they have defined,” he said. “Given that most of the cost of the intervention is up front, but the benefits are likely lifelong, potentially taking the 12-month analysis to a lifetime analysis would show more significant findings.”

Dr. Tam researches factors associated with brain injury rehabilitation and has explored the cost-effectiveness of a high-intensity outpatient stroke rehabilitation program.

“Presenting this type of work is important,” he said. “While there are interventions that do not meet our definition of statistical significance, especially in the rehabilitation world, there can still be a benefit for patients and health systems.”

The primary study was funded by the Canadian Institutes of Health Research (CIHR) and the Jack Brown and Family Alzheimer Research Foundation Society. Dr. Davis reported receiving grants from the CIHR and Michael Smith Health Research BC during the conduct of the study. Dr. Tam reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Using small-volume rather than standard-volume collection tubes to draw blood for laboratory testing may reduce the incidence of anemia and the need for red blood cell (RBC) transfusion in intensive care units (ICUs), according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.

In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.

“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.

“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”

The study was published online in JAMA.
 

Reducing Blood Loss

Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.

Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.

Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.

Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.

In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.

In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.

Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.

About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.

“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”

The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
 

Implementing Change

Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.

“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”

Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.

“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”

The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Using small-volume rather than standard-volume collection tubes to draw blood for laboratory testing may reduce the incidence of anemia and the need for red blood cell (RBC) transfusion in intensive care units (ICUs), according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.

In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.

“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.

“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”

The study was published online in JAMA.
 

Reducing Blood Loss

Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.

Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.

Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.

Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.

In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.

In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.

Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.

About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.

“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”

The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
 

Implementing Change

Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.

“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”

Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.

“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”

The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Using small-volume rather than standard-volume collection tubes to draw blood for laboratory testing may reduce the incidence of anemia and the need for red blood cell (RBC) transfusion in intensive care units (ICUs), according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.

In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.

“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.

“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”

The study was published online in JAMA.
 

Reducing Blood Loss

Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.

Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.

Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.

Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.

In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.

In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.

Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.

About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.

“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”

The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
 

Implementing Change

Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.

“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”

Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.

“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”

The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Pharmacogenomic testing for antidepressants could help reduce the time and cost it takes to find the most effective medication for a patient, according to a new study.

Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.

“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.

“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.

The study was published online on in the Canadian Medical Association Journal.
 

Developing a model

The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.

Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.

Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.

According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.

Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.

These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.

In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.

Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.

From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.

“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
 

Implementing the model

Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.

“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.

Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.

“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.

The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Pharmacogenomic testing for antidepressants could help reduce the time and cost it takes to find the most effective medication for a patient, according to a new study.

Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.

“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.

“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.

The study was published online on in the Canadian Medical Association Journal.
 

Developing a model

The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.

Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.

Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.

According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.

Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.

These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.

In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.

Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.

From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.

“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
 

Implementing the model

Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.

“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.

Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.

“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.

The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Pharmacogenomic testing for antidepressants could help reduce the time and cost it takes to find the most effective medication for a patient, according to a new study.

Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.

“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.

“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.

The study was published online on in the Canadian Medical Association Journal.
 

Developing a model

The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.

Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.

Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.

According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.

Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.

These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.

In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.

Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.

From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.

“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
 

Implementing the model

Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.

“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.

Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.

“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.

The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

Antibiotic pretreatment may protect against liver ischemia/reperfusion (I/R) injury through altered gut microbiota, glutamine levels, and glutamine downstream products in circulation, according to a recent study in Cellular and Molecular Gastroenterology and Hepatology.

The findings show that gut microbiota and their metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming, wrote Tianfei Lu, with the Abdominal Transplant Surgery Center at Ruijin Hospital and Shanghai Jiao Tong University, China, and colleagues.

“Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury,” the authors wrote.

Liver I/R injury is a common complication of liver resection, transplantation, trauma, and hemorrhagic shock. Previous studies have noted the important role of gut microbiota in liver disease progression, yet the mechanisms in liver I/R injury remain unknown.

The researchers pretreated mice with an antibiotic cocktail to modify the gut microbiome. They found that the pretreatment showed protective effects against hepatic I/R injury, with reductions in serum alanine aminotransferase (ALT), interleukin-1 beta, tumor necrosis factor–alpha, IL-6, IL-12b, and CXCL10.

Through histologic analysis of liver tissues, they also found that the area of necrosis, the degree of congestion and edema, and the presence of vacuole-like lesions were alleviated in the preconditioned mice. Inflammation and necrosis of the liver were also lower, according to both qualitative and quantitative data.

Then, through fecal microbiota transplantation into germ-free mice, they found that the protection from I/R injury was transferable. This finding indicated that the altered gut microbiome, rather than the antibiotic treatment itself, exerted the protective effect.

Because altered gut microbiota can cause changes in metabolites, the researchers used ultra-performance liquid chromatography coupled to tandem mass spectrometry to explore the changes of gut microbiota and metabolites in both feces and portal blood, as well as analyze the mechanisms underlying their protective effects in liver I/R injury.

The researchers found that glutamine and its downstream product called alpha-ketoglutarate (AKG) were present in higher concentrations in feces and blood in the mice with antibiotic pretreatment. Glutamate levels were significantly lower, indicating that glutamine is converted into AKG through glutamate after entering the blood.

In addition, there were increased levels of intermediate products of the tricarboxylic acid (TCA) cycle, as well as pyruvate produced by glycolysis. That led to an increase in M2 macrophages, which are responsible for anti-inflammatory processes and tissue repair.

The authors concluded that elevated glutamine levels in the intestine cause an increase in AKG levels in the blood, and AKG can promote M2 macrophage polarization by fueling the TCA cycle. In turn, the increased number of M2 macrophages can repair hepatic I/R injury.

Finally, the researchers tested oligomycin A, which can block the OXPHOS metabolic pathway and inhibit the mitochondrial ATP synthase. As expected, they wrote, the protective effect of antibiotic pretreatment reversed, M2 macrophages decreased, and serum ALT levels increased.

“The immunometabolism and polarization of macrophages play an important role in host homeostasis and the development of various diseases,” the authors wrote. “The relationship between antibiotics treatment, altered gut microbiota, and liver I/R injury are complex and worthy of further study.”

The study was supported by the China National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation exploration project of Zhejiang Province. The authors disclosed no conflicts.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

Vedolizumab appears to be effective at reducing intestinal inflammation and inducing remission in patients who developed chronic pouchitis after undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, according to a phase 4 trial.

The incidence of modified Pouchitis Disease Activity Index (mPDAI)–defined remission after 14 weeks was 31% for vedolizumab, compared with 10% for placebo.

“Vedolizumab works in both ulcerative colitis and Crohn’s disease, so it appeared rational to test its efficacy in chronic, antibiotic-resistant pouchitis,” lead author Simon Travis, DPhil, professor of clinical gastroenterology at the University of Oxford’s Kennedy Institute of Rheumatology and Translational Gastroenterology Unit in the United Kingdom, said in an interview.

“Vedolizumab works for antibiotic-resistant pouchitis,” he said. “It is the first advanced therapy licensed for chronic pouchitis in Europe and can be a game changer for patients who develop pouchitis after experiencing ulcerative colitis severe enough to need colectomy who might have thought that surgery would be the ultimate solution.”

The study was published online in The New England Journal of Medicine.


 

Treating chronic pouchitis

About half of patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA will develop pouchitis within 5 years, the authors write. Among those, about one-fifth will have chronic pouchitis, with symptoms that last longer than 4 weeks. Symptoms include increased stool frequency, abdominal pain, fecal urgency, and impaired quality of life.

Typically, antibiotics are recommended as first-line treatment for acute pouchitis, but antibiotic resistance is common. Previous studies have suggested that tumor necrosis factor antagonists and the monoclonal antibodies vedolizumab and ustekinumab may be effective in pouchitis that is refractory to antibiotics.

The U.S. Food and Drug Administration has approved vedolizumab as a treatment for moderate to severe ulcerative colitis and Crohn’s disease. In early 2022, the European Commission approved vedolizumab for adult patients with moderate to severe active chronic pouchitis who had undergone proctocolectomy with IPAA and had an inadequate response to antibiotic therapy. The approval was based on results from the EARNEST trial.

As part of the EARNEST trial, Dr. Travis and colleagues at 31 sites in North America and Europe conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab for chronic pouchitis after IPAA for ulcerative colitis.

Between October 2016 and March 2020, researchers identified 102 adult patients who met the study criteria. They were eligible if they had undergone proctocolectomy at least 1 year before screening and had active chronic pouchitis, which was defined by an mPDAI score of 5 or more and a minimum subscore of 2 on the endoscopic domain.

After a 28-day screening period, patients were randomly assigned in a 1:1 ratio to receive 300 mg of intravenous vedolizumab or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All patients also received 500 mg of oral ciprofloxacin twice daily from weeks 1 to 4. Additional courses of antibiotics were allowed, as needed, for pouchitis flares that occurred after week 14.

The primary endpoint was mPDAI-defined remission, or an mPDAI score of 4 or less and a reduction of 2 or more points on the 12-point scale at week 14.

Other endpoints included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction of 2 or more points) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of 6 or less and a reduction of 3 or more points on the 18-point scale) at weeks 14 and 34. The mPDAI is based on clinical symptoms and endoscopic findings, whereas the PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.

Overall, 36 patients (71%) in the vedolizumab group and 32 patients (63%) in the placebo group completed treatment and received all infusions through week 30. Eight patients in each group discontinued vedolizumab or placebo owing to a lack of efficacy. Demographic and clinical characteristics were similar in the two groups – about 84% of the patients were White, and the majority were men.

At the 14-week mark, 16 of 51 patients (31%) in the vedolizumab group and 5 of 51 patients (10%) in the placebo group achieved mPDAI-defined remission (a 21–percentage point difference; 95% CI, 5-38; P = .01). At week 34, 35% of the vedolizumab group and 18% of the placebo group reached remission. A post hoc analysis found that a high percentage of patients in the vedolizumab group reached remission regardless of whether concomitant antibiotics were used before week 14 or 34.

“Concomitant antibiotic use after week 4 was reported in a higher percentage of patients in the vedolizumab group than in the placebo group, a finding that was unexpected,” the authors write. “However, the use of additional antibiotics was not considered to be a treatment failure because antibiotics are the current standard of care for chronic pouchitis.”
 

Additional findings

Vedolizumab showed major differences in the other endpoints as well. The percentage of patients with PDAI-defined remission was 35% in the vedolizumab group versus 10% in the placebo group at week 14, and 37% versus 18% at week 34.

The percentage of patients with mPDAI-defined response at week 14 was 63% among the vedolizumab group and 33% among the placebo group. By week 34, the between-group difference was 51% versus 29%.

Vedolizumab also showed greater changes in total PDAI scores, including endoscopic and histologic subscores, as well as remission and response defined by the Inflammatory Bowel Disease Questionnaire (IBDQ). However, there were no significant differences in changes from baseline for the IBDQ or the Cleveland Global Quality of Life (CGQL) score.

The vedolizumab group had a higher percentage of patients with sustained mPDAI-defined remission (difference, 22 percentage points; 95% CI, 6-37) and sustained PDAI-defined remission (difference, 23 percentage points; 95% CI, 8-39).

Adverse events were reported in 47 patients (92%) in the vedolizumab group and 44 patients (86%) in the placebo group. Pouchitis was reported as an adverse event in 24 patients (47%) in the vedolizumab group and 20 patients (39%) in the placebo group. More patients in the vedolizumab group also reported upper respiratory tract infections and headaches.

Serious adverse events occurred in three patients (6%) in the vedolizumab group and four patients (8%) in the placebo group. One adverse event led to discontinuation of vedolizumab, and no serious adverse events were related to vedolizumab or led to discontinuation of vedolizumab.
 

‘Landmark study’

“This is a landmark study that shows us that a biologic that we have used for Crohn’s disease and ulcerative colitis may also be used to treat chronic pouchitis. This is a large unmet need for our patients and an important advancement for the field,” Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, told this news organization.

The Cleveland Clinic has one of the highest referral rates in the country for IPAA, noted Dr. Regueiro, who wasn’t involved with this study. Colleagues are currently conducting studies to determine who may develop pouchitis and understand why certain patients develop pouchitis after the procedure, he said.

One question the EARNEST trial leaves unanswered is whether vedolizumab will be required as a sustained medicine to control pouchitis or could be stopped at some point, he said. “My sense is that, as is the case with any IBD, chronic treatment will be required,” he added.

The higher rate of ciprofloxacin use among patients who received vedolizumab is interesting, Dr. Regueiro said.

“[The researchers] note that ciprofloxacin was used for symptoms and do not know if there was active inflammation. It’s possible that bacterial overgrowth caused symptoms and the antibiotic treated that, and in a study this small, it is difficult to say anything more,” he said.

The study was sponsored by Takeda, the manufacturer of vedolizumab. Several authors reported speaking fees and consultant roles for numerous pharmaceutical companies, including Takeda. Three of the authors are employees of Takeda. Dr. Regueiro reported no relevant disclosures.

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

Vedolizumab appears to be effective at reducing intestinal inflammation and inducing remission in patients who developed chronic pouchitis after undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, according to a phase 4 trial.

The incidence of modified Pouchitis Disease Activity Index (mPDAI)–defined remission after 14 weeks was 31% for vedolizumab, compared with 10% for placebo.

“Vedolizumab works in both ulcerative colitis and Crohn’s disease, so it appeared rational to test its efficacy in chronic, antibiotic-resistant pouchitis,” lead author Simon Travis, DPhil, professor of clinical gastroenterology at the University of Oxford’s Kennedy Institute of Rheumatology and Translational Gastroenterology Unit in the United Kingdom, said in an interview.

“Vedolizumab works for antibiotic-resistant pouchitis,” he said. “It is the first advanced therapy licensed for chronic pouchitis in Europe and can be a game changer for patients who develop pouchitis after experiencing ulcerative colitis severe enough to need colectomy who might have thought that surgery would be the ultimate solution.”

The study was published online in The New England Journal of Medicine.


 

Treating chronic pouchitis

About half of patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA will develop pouchitis within 5 years, the authors write. Among those, about one-fifth will have chronic pouchitis, with symptoms that last longer than 4 weeks. Symptoms include increased stool frequency, abdominal pain, fecal urgency, and impaired quality of life.

Typically, antibiotics are recommended as first-line treatment for acute pouchitis, but antibiotic resistance is common. Previous studies have suggested that tumor necrosis factor antagonists and the monoclonal antibodies vedolizumab and ustekinumab may be effective in pouchitis that is refractory to antibiotics.

The U.S. Food and Drug Administration has approved vedolizumab as a treatment for moderate to severe ulcerative colitis and Crohn’s disease. In early 2022, the European Commission approved vedolizumab for adult patients with moderate to severe active chronic pouchitis who had undergone proctocolectomy with IPAA and had an inadequate response to antibiotic therapy. The approval was based on results from the EARNEST trial.

As part of the EARNEST trial, Dr. Travis and colleagues at 31 sites in North America and Europe conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab for chronic pouchitis after IPAA for ulcerative colitis.

Between October 2016 and March 2020, researchers identified 102 adult patients who met the study criteria. They were eligible if they had undergone proctocolectomy at least 1 year before screening and had active chronic pouchitis, which was defined by an mPDAI score of 5 or more and a minimum subscore of 2 on the endoscopic domain.

After a 28-day screening period, patients were randomly assigned in a 1:1 ratio to receive 300 mg of intravenous vedolizumab or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All patients also received 500 mg of oral ciprofloxacin twice daily from weeks 1 to 4. Additional courses of antibiotics were allowed, as needed, for pouchitis flares that occurred after week 14.

The primary endpoint was mPDAI-defined remission, or an mPDAI score of 4 or less and a reduction of 2 or more points on the 12-point scale at week 14.

Other endpoints included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction of 2 or more points) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of 6 or less and a reduction of 3 or more points on the 18-point scale) at weeks 14 and 34. The mPDAI is based on clinical symptoms and endoscopic findings, whereas the PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.

Overall, 36 patients (71%) in the vedolizumab group and 32 patients (63%) in the placebo group completed treatment and received all infusions through week 30. Eight patients in each group discontinued vedolizumab or placebo owing to a lack of efficacy. Demographic and clinical characteristics were similar in the two groups – about 84% of the patients were White, and the majority were men.

At the 14-week mark, 16 of 51 patients (31%) in the vedolizumab group and 5 of 51 patients (10%) in the placebo group achieved mPDAI-defined remission (a 21–percentage point difference; 95% CI, 5-38; P = .01). At week 34, 35% of the vedolizumab group and 18% of the placebo group reached remission. A post hoc analysis found that a high percentage of patients in the vedolizumab group reached remission regardless of whether concomitant antibiotics were used before week 14 or 34.

“Concomitant antibiotic use after week 4 was reported in a higher percentage of patients in the vedolizumab group than in the placebo group, a finding that was unexpected,” the authors write. “However, the use of additional antibiotics was not considered to be a treatment failure because antibiotics are the current standard of care for chronic pouchitis.”
 

Additional findings

Vedolizumab showed major differences in the other endpoints as well. The percentage of patients with PDAI-defined remission was 35% in the vedolizumab group versus 10% in the placebo group at week 14, and 37% versus 18% at week 34.

The percentage of patients with mPDAI-defined response at week 14 was 63% among the vedolizumab group and 33% among the placebo group. By week 34, the between-group difference was 51% versus 29%.

Vedolizumab also showed greater changes in total PDAI scores, including endoscopic and histologic subscores, as well as remission and response defined by the Inflammatory Bowel Disease Questionnaire (IBDQ). However, there were no significant differences in changes from baseline for the IBDQ or the Cleveland Global Quality of Life (CGQL) score.

The vedolizumab group had a higher percentage of patients with sustained mPDAI-defined remission (difference, 22 percentage points; 95% CI, 6-37) and sustained PDAI-defined remission (difference, 23 percentage points; 95% CI, 8-39).

Adverse events were reported in 47 patients (92%) in the vedolizumab group and 44 patients (86%) in the placebo group. Pouchitis was reported as an adverse event in 24 patients (47%) in the vedolizumab group and 20 patients (39%) in the placebo group. More patients in the vedolizumab group also reported upper respiratory tract infections and headaches.

Serious adverse events occurred in three patients (6%) in the vedolizumab group and four patients (8%) in the placebo group. One adverse event led to discontinuation of vedolizumab, and no serious adverse events were related to vedolizumab or led to discontinuation of vedolizumab.
 

‘Landmark study’

“This is a landmark study that shows us that a biologic that we have used for Crohn’s disease and ulcerative colitis may also be used to treat chronic pouchitis. This is a large unmet need for our patients and an important advancement for the field,” Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, told this news organization.

The Cleveland Clinic has one of the highest referral rates in the country for IPAA, noted Dr. Regueiro, who wasn’t involved with this study. Colleagues are currently conducting studies to determine who may develop pouchitis and understand why certain patients develop pouchitis after the procedure, he said.

One question the EARNEST trial leaves unanswered is whether vedolizumab will be required as a sustained medicine to control pouchitis or could be stopped at some point, he said. “My sense is that, as is the case with any IBD, chronic treatment will be required,” he added.

The higher rate of ciprofloxacin use among patients who received vedolizumab is interesting, Dr. Regueiro said.

“[The researchers] note that ciprofloxacin was used for symptoms and do not know if there was active inflammation. It’s possible that bacterial overgrowth caused symptoms and the antibiotic treated that, and in a study this small, it is difficult to say anything more,” he said.

The study was sponsored by Takeda, the manufacturer of vedolizumab. Several authors reported speaking fees and consultant roles for numerous pharmaceutical companies, including Takeda. Three of the authors are employees of Takeda. Dr. Regueiro reported no relevant disclosures.

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

Vedolizumab appears to be effective at reducing intestinal inflammation and inducing remission in patients who developed chronic pouchitis after undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, according to a phase 4 trial.

The incidence of modified Pouchitis Disease Activity Index (mPDAI)–defined remission after 14 weeks was 31% for vedolizumab, compared with 10% for placebo.

“Vedolizumab works in both ulcerative colitis and Crohn’s disease, so it appeared rational to test its efficacy in chronic, antibiotic-resistant pouchitis,” lead author Simon Travis, DPhil, professor of clinical gastroenterology at the University of Oxford’s Kennedy Institute of Rheumatology and Translational Gastroenterology Unit in the United Kingdom, said in an interview.

“Vedolizumab works for antibiotic-resistant pouchitis,” he said. “It is the first advanced therapy licensed for chronic pouchitis in Europe and can be a game changer for patients who develop pouchitis after experiencing ulcerative colitis severe enough to need colectomy who might have thought that surgery would be the ultimate solution.”

The study was published online in The New England Journal of Medicine.


 

Treating chronic pouchitis

About half of patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA will develop pouchitis within 5 years, the authors write. Among those, about one-fifth will have chronic pouchitis, with symptoms that last longer than 4 weeks. Symptoms include increased stool frequency, abdominal pain, fecal urgency, and impaired quality of life.

Typically, antibiotics are recommended as first-line treatment for acute pouchitis, but antibiotic resistance is common. Previous studies have suggested that tumor necrosis factor antagonists and the monoclonal antibodies vedolizumab and ustekinumab may be effective in pouchitis that is refractory to antibiotics.

The U.S. Food and Drug Administration has approved vedolizumab as a treatment for moderate to severe ulcerative colitis and Crohn’s disease. In early 2022, the European Commission approved vedolizumab for adult patients with moderate to severe active chronic pouchitis who had undergone proctocolectomy with IPAA and had an inadequate response to antibiotic therapy. The approval was based on results from the EARNEST trial.

As part of the EARNEST trial, Dr. Travis and colleagues at 31 sites in North America and Europe conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab for chronic pouchitis after IPAA for ulcerative colitis.

Between October 2016 and March 2020, researchers identified 102 adult patients who met the study criteria. They were eligible if they had undergone proctocolectomy at least 1 year before screening and had active chronic pouchitis, which was defined by an mPDAI score of 5 or more and a minimum subscore of 2 on the endoscopic domain.

After a 28-day screening period, patients were randomly assigned in a 1:1 ratio to receive 300 mg of intravenous vedolizumab or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All patients also received 500 mg of oral ciprofloxacin twice daily from weeks 1 to 4. Additional courses of antibiotics were allowed, as needed, for pouchitis flares that occurred after week 14.

The primary endpoint was mPDAI-defined remission, or an mPDAI score of 4 or less and a reduction of 2 or more points on the 12-point scale at week 14.

Other endpoints included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction of 2 or more points) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of 6 or less and a reduction of 3 or more points on the 18-point scale) at weeks 14 and 34. The mPDAI is based on clinical symptoms and endoscopic findings, whereas the PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.

Overall, 36 patients (71%) in the vedolizumab group and 32 patients (63%) in the placebo group completed treatment and received all infusions through week 30. Eight patients in each group discontinued vedolizumab or placebo owing to a lack of efficacy. Demographic and clinical characteristics were similar in the two groups – about 84% of the patients were White, and the majority were men.

At the 14-week mark, 16 of 51 patients (31%) in the vedolizumab group and 5 of 51 patients (10%) in the placebo group achieved mPDAI-defined remission (a 21–percentage point difference; 95% CI, 5-38; P = .01). At week 34, 35% of the vedolizumab group and 18% of the placebo group reached remission. A post hoc analysis found that a high percentage of patients in the vedolizumab group reached remission regardless of whether concomitant antibiotics were used before week 14 or 34.

“Concomitant antibiotic use after week 4 was reported in a higher percentage of patients in the vedolizumab group than in the placebo group, a finding that was unexpected,” the authors write. “However, the use of additional antibiotics was not considered to be a treatment failure because antibiotics are the current standard of care for chronic pouchitis.”
 

Additional findings

Vedolizumab showed major differences in the other endpoints as well. The percentage of patients with PDAI-defined remission was 35% in the vedolizumab group versus 10% in the placebo group at week 14, and 37% versus 18% at week 34.

The percentage of patients with mPDAI-defined response at week 14 was 63% among the vedolizumab group and 33% among the placebo group. By week 34, the between-group difference was 51% versus 29%.

Vedolizumab also showed greater changes in total PDAI scores, including endoscopic and histologic subscores, as well as remission and response defined by the Inflammatory Bowel Disease Questionnaire (IBDQ). However, there were no significant differences in changes from baseline for the IBDQ or the Cleveland Global Quality of Life (CGQL) score.

The vedolizumab group had a higher percentage of patients with sustained mPDAI-defined remission (difference, 22 percentage points; 95% CI, 6-37) and sustained PDAI-defined remission (difference, 23 percentage points; 95% CI, 8-39).

Adverse events were reported in 47 patients (92%) in the vedolizumab group and 44 patients (86%) in the placebo group. Pouchitis was reported as an adverse event in 24 patients (47%) in the vedolizumab group and 20 patients (39%) in the placebo group. More patients in the vedolizumab group also reported upper respiratory tract infections and headaches.

Serious adverse events occurred in three patients (6%) in the vedolizumab group and four patients (8%) in the placebo group. One adverse event led to discontinuation of vedolizumab, and no serious adverse events were related to vedolizumab or led to discontinuation of vedolizumab.
 

‘Landmark study’

“This is a landmark study that shows us that a biologic that we have used for Crohn’s disease and ulcerative colitis may also be used to treat chronic pouchitis. This is a large unmet need for our patients and an important advancement for the field,” Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, told this news organization.

The Cleveland Clinic has one of the highest referral rates in the country for IPAA, noted Dr. Regueiro, who wasn’t involved with this study. Colleagues are currently conducting studies to determine who may develop pouchitis and understand why certain patients develop pouchitis after the procedure, he said.

One question the EARNEST trial leaves unanswered is whether vedolizumab will be required as a sustained medicine to control pouchitis or could be stopped at some point, he said. “My sense is that, as is the case with any IBD, chronic treatment will be required,” he added.

The higher rate of ciprofloxacin use among patients who received vedolizumab is interesting, Dr. Regueiro said.

“[The researchers] note that ciprofloxacin was used for symptoms and do not know if there was active inflammation. It’s possible that bacterial overgrowth caused symptoms and the antibiotic treated that, and in a study this small, it is difficult to say anything more,” he said.

The study was sponsored by Takeda, the manufacturer of vedolizumab. Several authors reported speaking fees and consultant roles for numerous pharmaceutical companies, including Takeda. Three of the authors are employees of Takeda. Dr. Regueiro reported no relevant disclosures.

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

Semaglutide didn’t significantly improve liver fibrosis or achieve resolution of nonalcoholic steatohepatitis (NASH)–related compensated cirrhosis, compared with placebo, according to a phase 2 trial.

However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.

“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.

“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.

The study was published online  in The Lancet Gastroenterology & Hepatology.
 

Analyzing safety and efficacy

Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m² were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.

Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.

The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.

Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.

Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.

After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).

There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).

In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
 

Some improvements seen

However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.

Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.

Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.

The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.

“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
 

Considering next steps

Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.

Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.

“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.

Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.

Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.

“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.

“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”

In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.

“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”

At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.

“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”

The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.

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

Semaglutide didn’t significantly improve liver fibrosis or achieve resolution of nonalcoholic steatohepatitis (NASH)–related compensated cirrhosis, compared with placebo, according to a phase 2 trial.

However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.

“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.

“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.

The study was published online  in The Lancet Gastroenterology & Hepatology.
 

Analyzing safety and efficacy

Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m² were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.

Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.

The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.

Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.

Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.

After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).

There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).

In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
 

Some improvements seen

However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.

Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.

Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.

The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.

“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
 

Considering next steps

Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.

Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.

“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.

Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.

Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.

“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.

“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”

In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.

“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”

At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.

“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”

The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.

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

Semaglutide didn’t significantly improve liver fibrosis or achieve resolution of nonalcoholic steatohepatitis (NASH)–related compensated cirrhosis, compared with placebo, according to a phase 2 trial.

However, the glucagonlike peptide–1 (GLP-1) receptor agonist led to improvements in liver enzymes, liver steatosis, weight, triglycerides, and very low-density lipoprotein (VLDL) cholesterol. Similar proportions of patients in each group reported adverse events, such as nausea, diarrhea, and vomiting.

“Previous studies in patients with NASH and stage 2 or 3 fibrosis have shown that semaglutide can improve NASH resolution over 72 weeks. However, there are limited data on whether any therapy is effective in patients with NASH cirrhosis,” lead author Rohit Loomba, MD, founding director of the NAFLD Research Center at the University of California, San Diego, said in an interview.

“Although semaglutide did not succeed in improving histological fibrosis, it had success in improving other clinically important parameters, such as cardiometabolic risk factors, liver enzymes, liver fat, and noninvasive biomarkers of fibrosis,” he said.

The study was published online  in The Lancet Gastroenterology & Hepatology.
 

Analyzing safety and efficacy

Dr. Loomba and colleagues conducted a double-blind, placebo-controlled phase 2 trial that enrolled 71 patients at 38 centers in the United States and Europe between June 2019 and April 2021. Adults with biopsy-confirmed NASH-related cirrhosis and a body mass index (BMI) of at least 27 kg/m² were randomly assigned 2:1 to receive either once-weekly subcutaneous semaglutide at 2.4 mg or a visually matching placebo.

Patients were randomly allocated through an interactive web system, which stratified participants on the basis of the presence or absence of type 2 diabetes. Patients, investigators, and outcomes analysts were masked to the treatment assignment.

The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without a worsening of NASH after 48 weeks, which was measured through biopsy in the intention-to-treat population. Safety was also assessed in all patients who received at least one dose of semaglutide.

Among the 71 patients, 47 were randomly assigned to the semaglutide group and 24 to the placebo group. About 90% completed treatment, and 63 had evaluable paired biopsies for primary endpoint assessment.

Between the groups, 49 participants (69%) were women and 22 were men. The average age was 59.5 years, and the average BMI was 34.9. About 75% of patients had diabetes at baseline, with an average hemoglobin A1c of 7.1%.

After 48 weeks, researchers found no statistically significant difference between the groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH. In the semaglutide group, five patients (11%) had an improvement, compared with seven patients (29%) in the placebo group (odds ratio, 0.28; 95% confidence interval, 0.06-1.24, P = .087).

There also wasn’t a significant difference between groups in the proportion of patients who achieved NASH resolution. In the semaglutide group, 16 patients (34%) had resolution, compared with 5 patients (21%) in the placebo group (OR, 1.97; 95% CI, 0.56-7.91; P = .29).

In addition, a lower proportion of patients achieved both NASH resolution and improvement in liver fibrosis with semaglutide versus placebo, although the difference wasn’t significant. In the semaglutide group, three patients (6%) achieved both, compared with three patients (13%) in the placebo group (OR, 0.48; 95% CI, 0.06-3.91; P = .4). A lower proportion of patients had an improvement in liver fibrosis stage with semaglutide versus placebo.
 

Some improvements seen

However, the semaglutide group had significantly greater improvements in liver steatosis (but not stiffness), liver fat volume, procollagen 3 peptide, and liver enzymes such as ALT, AST, and gamma-glutamyltransferase.

Body weight decreased by 8.83% in the semaglutide group, compared with 0.09% in the placebo group, which was a significant difference. BMI, waist circumference, triglycerides, and VLDL cholesterol were also significantly lower in the semaglutide group, but total cholesterol and blood pressure measurements weren’t significantly different. Among those with type 2 diabetes, A1c also decreased in the semaglutide group but did not in the placebo group.

Similar proportions of patients in each group reported adverse events. In the semaglutide group, 42 patients (89%) had an adverse event, compared with 19 patients (79%) in the placebo group. In addition, six patients (13%) in the semaglutide group and two patients (8%) in the placebo group reported serious adverse events.

The most common adverse events in the semaglutide and placebo groups were nausea (45% and 17%), diarrhea (19% and 8%), and vomiting (17% and none), which mainly occurred during treatment initiation or dose escalation. No patients withdrew from the trial because of adverse events, although five had a dose reduction. Hepatic and renal function remained stable after semaglutide treatment, and there were no decompensating events or deaths.

“GLP-1 analogue exposure – among patients with compensated cirrhosis who suffer from morbid obesity and type 2 diabetes – for the treatment of diabetes appears to be well-tolerated and may be safe,” Dr. Loomba said. “Further studies are needed in this study population.”
 

Considering next steps

Dr. Loomba and colleagues are continuing research around risk factors linked to advanced fibrosis, such as type 2 diabetes, a family history of cirrhosis, and the presence of key genetic risk alleles. Gut dysbiosis also appears to increase the risk for advanced fatty liver disease, he said.

Future clinical trials could focus on therapeutic options for patients with advanced fibrosis, particularly those with cirrhosis who face increased risks for liver-related complications and mortality.

“As these patients are oftentimes excluded from initial randomized controlled trials, we have significantly less information on how to address obesity, type 2 diabetes, and NASH in these patients,” Fernando Bril, MD, a physician-scientist focused on NASH-related research at the University of Alabama at Birmingham, said in an interview.

Dr. Bril, who wasn’t involved with this study, wrote an accompanying editorial in The Lancet Gastroenterology & Hepatology.

Patients with NASH-related cirrhosis may have progressed to a point of the disease where fibrosis regression may be more difficult to achieve, he said.

“This emphasizes that early diagnosis of patients with NASH is crucial,” he said.

“Therefore, primary care providers, endocrinologists, and diabetologists need to have a low threshold to suspect liver disease in patients with overweight, obesity, and/or type 2 diabetes. Only this will allow for early initiation of therapy, which may delay the progression of liver disease.”

In further research, investigators may want to consider the lack of NASH resolution, a result that could be caused by this study being underpowered, Dr. Bril noted. The trend in resolution in this study appeared similar to improvements seen in NASH patients without cirrhosis in other studies, he said. The weight reduction and improved diabetes control in this group also shows promise.

“While a purist may be adamant that this was a negative study for histological outcomes, it is essential to take note of the positive results in many secondary outcomes,” he said. “Improving cardiometabolic risk in these patients is essential because many still die of cardiovascular disease and not liver-related complications.”

At the same time, it’s important to note that NASH can’t be oversimplified as “a matter of weight,” Dr. Bril said. Significant weight loss in the study didn’t result in histologic improvement, which means other strategies are needed to treat the disease.

“Negative results from this study emphasize that monotherapy may not be enough to improve NASH and liver fibrosis,” he said. “In a similar way we treat type 2 diabetes and hypertension with combination therapy, we need to consider a similar approach for patients with NASH.”

The study was sponsored by Novo Nordisk, which manufactures semaglutide. The authors declared grant funding, speaker fees, and consultant roles with numerous pharmaceutical companies. Dr. Bril had no relevant disclosures.

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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