Federal Practitioner

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.

In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.

“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.

“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.

“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing bleed rates

Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.

Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.

Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.

In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.

Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.

Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.

Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.

“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.

Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.

“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
 

Considering future research

In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.

“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.

Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.

In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.

“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”

Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.

“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”

The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

The influenza vaccine is linked to a significantly lower risk of ischemic stroke, with the reduced risk apparent at a population level even outside of flu season, in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.

“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.

Jovanmandic/Thinkstock

“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”

The study was published online in Neurology.
 

‘Not a spurious association’

While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.

In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.

Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).

Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).

Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).

The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.

The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.

Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).

“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
 

Anti-inflammatory effect?

Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.

The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.

“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.

In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.

“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.
 

‘More than just flu prevention’

In an accompanying editorial, Dixon Yang, MD, and Mitchell S.V. Elkind, MD, agree that the findings point to intriguing potential unexpected benefits of the vaccine.

“This case-control study ... importantly suggests the influenza vaccine is more than just about preventing the flu,” they wrote.

Dr. Elkind said in an interview that the mechanism could indeed involve an anti-inflammatory effect.

“There is some evidence that antibiotics also have anti-inflammatory properties that might reduce risk of stroke or the brain damage from a stroke,” he noted. “So, it is plausible that some of the effect of the vaccine on reducing risk of stroke may be through a reduction in inflammation.”

Dr. Elkind noted that the magnitude of the reduction observed with the vaccine, though not substantial, is important. “The magnitude of effect for any one individual may be modest, but it is in the ballpark of the effect of other commonly used approaches to stroke prevention, such as taking an aspirin a day, which reduces risk of stroke by about 20%. But because influenza is so common, the impact of even a small effect for an individual can have a large impact at the population level. So, the results are of public health significance.”

The study received support from the Biomedical Research Foundation of the Prince of Asturias University Hospital and the Institute of Health Carlos III in Madrid. Dr. Elkind has reported receiving ancillary funding but no personal compensation from Roche for a federally funded trial of stroke prevention.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

New data suggest that for individuals who do not have an adenoma detected on an index colonoscopy, the risk of developing an advanced neoplasia (AN) and colorectal cancer (CRC) is lower in those who are aged 40-49 years, compared with those who are 50-59 years old.

However, there is no difference between the two age groups in detection rates of nonadvanced adenoma (NAA) or advanced adenoma (AA), the same study found.

“The primary goal of this study was to investigate the risk of metachronous AN associated with conventional adenoma detected on the index colonoscopy,” explain the authors, led by Gene Ma, MD, Kaiser Permanente Northern California, San Jose.

“The lack of good-quality evidence to inform surveillance in the 40-49 year old population has resulted in inconsistent surveillance patterns in clinical practice, leading to variation in the quality of care, including both inadequate and excessive colonoscopic surveillance,” Dr. Ma and colleagues observe.

The findings from this study “expand our understanding of the risk of AN and CRC in younger individuals and suggest that the current multi-society guidelines for surveillance may be applicable for individuals 40-49 years of age,” the authors conclude.

The study was published online in The American Journal of Gastroenterology, and included 2,396 individuals between 40 and 49 years of age and 8,978 individuals between 50 and 59 years of age.

The colonoscopy was carried out for screening in 40.2% in the younger age group versus 34.8% in the older age group and was prompted by a positive fecal immunochemical test in 3.3% of the younger age group versus 32% of the older age group.

The median follow-up for both age groups was roughly 7 years.

“When comparing the 40-49 years group to the 50-59 years group, index colonoscopy detected no adenoma in 62.9% versus 40.1% (P < .0001); NAA in 25.4% versus 39.0% (P <.001), and AA in 11.6% versus 21.0% (P < .0001), respectively,” Dr. Ma and colleagues report.

When the two age groups were compared for surveillance colonoscopy, no adenoma was detected in 67% of the younger age group versus 54.7% of the older age group (P < .0001), whereas NAA was detected in 25.4% of the 40- to 49-year-olds versus 38.4% of the 50- to 59-year-olds (P < .0001). AA was detected in 3.5% versus 6.95 (P < .0001) of persons in each of the two age groups, respectively.

AN was detected on surveillance colonoscopy after index colonoscopy in 2.2% of the younger age group and twice that percentage, at 4.4%, in the older age group (P = .0003). On surveillance colonoscopy, NAA was found in 4.6% of the younger age group, compared with 7% of the older age group (P = .03), whereas AA was found in 7.9% of the 40- to 49-year-olds, compared with 11.7% of the 50- to 59-year-olds (P = .06).

The median time until surveillance colonoscopy was similar in both age groups when either NAA or AA was found on index colonoscopy, the authors note. In addition, the median time until the detection of AN was similar whether NAA or AA was detected on index colonoscopy, they add.

The overall crude cumulative incidence of AN was lower in the younger age group when no adenoma was detected on index colonoscopy (P = .0003) as well as when NAA was detected, which would be consistent with recommendations from current guidelines for surveillance colonoscopy after adenoma detection. However, there was no difference between the two age groups in the overall cumulative incidence of AN when AA was detected on index colonoscopy.

Overall, the risk for metachronous AN in persons aged 40-49 years was lower when no adenoma was detected on index colonoscopy, but there was no difference between the two age groups when NAA or AA was detected again on index colonoscopy. Similarly, those aged 40-49 years of age had a lower risk for AA or CRC when no adenoma was detected on index colonoscopy – but again, there was no difference in the risk for AA or CRC when either NAA or AA was detected on index colonoscopy.

The authors have no conflicts of interest to report.

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

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.

Psychiatrists’ perceptions of the safety, therapeutic value, and abuse potential of psychoactive drugs are inconsistent with current drug policy, results from a new survey show.

“The consensus among experts, including psychiatrists, about specific drugs is not consistent or congruent with the schedule of these drugs” in the United States, lead author Adam Levin, MD, third-year psychiatry resident, Ohio State University, Columbus, and affiliate scholar at the Center for Psychedelic Drug Research and Education, Ohio State College of Social Work, told this news organization.

Dr. Levin stressed the importance of appropriate drug scheduling to improve access to treatments such as psilocybin (psychedelic mushrooms) and 4-methylenedioxy methamphetamine (MDMA), which are now being tested for psychiatric disorders.

“We are in the middle of a mental health crisis so having any new tools would be really important,” he said.

The survey findings were published online  in the International Journal of Drug Policy.
 

Five drug schedules

The Controlled Substances Act of 1970 created five “schedules” that organized drugs from most to least dangerous (schedule I-V). However, Dr. Levin said that the schedules do not accurately reflect the harms or therapeutic benefits of the various drugs.

Some drugs in lower, less restrictive schedules have greater potential for harm than do those in higher schedules, he noted. For example, methamphetamine, which has been recalled in multiple formulations because of concerns about abuse and limited medical use, remains a schedule II drug.

In addition, several schedule I drugs, including psilocybin and MDMA that are deemed dangerous and of no medical value, have shown therapeutic potential and low rates of misuse, addiction, or physical harm, the investigators noted.

In fact, the Food and Drug Administration has granted breakthrough therapy status to psilocybin for treatment-resistant depression and major depressive disorder (MDD) and to MDMA for posttraumatic stress disorder. This has positioned these drugs for possible FDA approval within the next few years.

Access to schedule I drugs for research purposes is tightly controlled. “Once psilocybin was placed in schedule I, there was this massive drop-off in the research funding and amount of research; and we’re just now starting to understand the potential therapeutic value of this drug,” said Dr. Levin.

Even with a recent research resurgence, most studies are funded by charitable donations or for-profit companies because of continued hesitancy on the part of grant-making organizations, he added.
 

Apparent contradictions

Given the pending approval of several schedule I drugs and escalating abuse of drugs in lower schedules, there is a growing need to understand physician attitudes surrounding the apparent contradictions in the drug schedule, the investigators noted.

Their survey included a geographically diverse group of 181 mostly middle-aged psychiatrists (65.2% were men) with an average of 16.2 years of practice after residency.

Participants were randomly assigned to respond to a vignette depicting a clinical scenario where a patient wants one of four drugs to help treat severe depression: psilocybin, a schedule I drug; methamphetamine (Desoxyn), a schedule II drug; ketamine, a Schedule III drug; or alprazolam (Xanax), a schedule IV drug.

Each of these therapies has established antidepressant properties, but none are FDA approved for treatment of MDD. However, an intranasal formulation of the ketamine enantiomer Spravato (esketamine) was recently approved for treatment-resistant depression.

There were significant differences among the groups presented with different vignettes. Participants were more likely to warn against repeated use of and development of a new psychiatric problem with methamphetamine and alprazolam compared with psilocybin or ketamine.

Respondents were most concerned about increased suicide risk after the nonprescribed use of alprazolam compared with psilocybin and ketamine.

Compared with all other drugs, ketamine was more likely to be integrated into treatment plans.
 

Therapeutic value, abuse potential

Participants were asked to rate the safety, therapeutic value, and abuse potential of the four drugs as well as alcohol, a nonscheduled legal drug, if used properly or as directed.

Respondents viewed psilocybin and ketamine as similarly safe – and safer than methamphetamine and alprazolam. They considered ketamine as having the highest therapeutic potential, followed by psilocybin, and then alprazolam and methamphetamine. “Last was alcohol, which we expected because alcohol is not used therapeutically,” said Dr. Levin.

Survey completers viewed methamphetamine, alprazolam, and alcohol as having similarly high abuse potential, and ketamine as having mid-level abuse potential. Psilocybin was rated as having the lowest abuse potential, “which is exactly the opposite of what is implied by its schedule I status,” noted Dr. Levin.

The results provide evidence these drugs “are incorrectly scheduled,” he said.

“This suggests the schedule does not reflect current evidence, which I think is really important to understand because there are consequences to the drug schedule,” including criminal justice and research consequences, he added.

Dr. Levin pointed out that possession of drugs in more harmful schedules is linked to sometimes lengthy prison sentences.

The psychiatrists’ perceptions of the drugs “overlaps pretty significantly” with recent surveys of other mental health professionals, including psychologists and addiction experts, he noted.

The study was funded by the Drug Enforcement and Policy Center, Moritz College of Law, and The Ohio State University. Dr. Levin reported no relevant financial relationships.

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

Psychiatrists’ perceptions of the safety, therapeutic value, and abuse potential of psychoactive drugs are inconsistent with current drug policy, results from a new survey show.

“The consensus among experts, including psychiatrists, about specific drugs is not consistent or congruent with the schedule of these drugs” in the United States, lead author Adam Levin, MD, third-year psychiatry resident, Ohio State University, Columbus, and affiliate scholar at the Center for Psychedelic Drug Research and Education, Ohio State College of Social Work, told this news organization.

Dr. Levin stressed the importance of appropriate drug scheduling to improve access to treatments such as psilocybin (psychedelic mushrooms) and 4-methylenedioxy methamphetamine (MDMA), which are now being tested for psychiatric disorders.

“We are in the middle of a mental health crisis so having any new tools would be really important,” he said.

The survey findings were published online  in the International Journal of Drug Policy.
 

Five drug schedules

The Controlled Substances Act of 1970 created five “schedules” that organized drugs from most to least dangerous (schedule I-V). However, Dr. Levin said that the schedules do not accurately reflect the harms or therapeutic benefits of the various drugs.

Some drugs in lower, less restrictive schedules have greater potential for harm than do those in higher schedules, he noted. For example, methamphetamine, which has been recalled in multiple formulations because of concerns about abuse and limited medical use, remains a schedule II drug.

In addition, several schedule I drugs, including psilocybin and MDMA that are deemed dangerous and of no medical value, have shown therapeutic potential and low rates of misuse, addiction, or physical harm, the investigators noted.

In fact, the Food and Drug Administration has granted breakthrough therapy status to psilocybin for treatment-resistant depression and major depressive disorder (MDD) and to MDMA for posttraumatic stress disorder. This has positioned these drugs for possible FDA approval within the next few years.

Access to schedule I drugs for research purposes is tightly controlled. “Once psilocybin was placed in schedule I, there was this massive drop-off in the research funding and amount of research; and we’re just now starting to understand the potential therapeutic value of this drug,” said Dr. Levin.

Even with a recent research resurgence, most studies are funded by charitable donations or for-profit companies because of continued hesitancy on the part of grant-making organizations, he added.
 

Apparent contradictions

Given the pending approval of several schedule I drugs and escalating abuse of drugs in lower schedules, there is a growing need to understand physician attitudes surrounding the apparent contradictions in the drug schedule, the investigators noted.

Their survey included a geographically diverse group of 181 mostly middle-aged psychiatrists (65.2% were men) with an average of 16.2 years of practice after residency.

Participants were randomly assigned to respond to a vignette depicting a clinical scenario where a patient wants one of four drugs to help treat severe depression: psilocybin, a schedule I drug; methamphetamine (Desoxyn), a schedule II drug; ketamine, a Schedule III drug; or alprazolam (Xanax), a schedule IV drug.

Each of these therapies has established antidepressant properties, but none are FDA approved for treatment of MDD. However, an intranasal formulation of the ketamine enantiomer Spravato (esketamine) was recently approved for treatment-resistant depression.

There were significant differences among the groups presented with different vignettes. Participants were more likely to warn against repeated use of and development of a new psychiatric problem with methamphetamine and alprazolam compared with psilocybin or ketamine.

Respondents were most concerned about increased suicide risk after the nonprescribed use of alprazolam compared with psilocybin and ketamine.

Compared with all other drugs, ketamine was more likely to be integrated into treatment plans.
 

Therapeutic value, abuse potential

Participants were asked to rate the safety, therapeutic value, and abuse potential of the four drugs as well as alcohol, a nonscheduled legal drug, if used properly or as directed.

Respondents viewed psilocybin and ketamine as similarly safe – and safer than methamphetamine and alprazolam. They considered ketamine as having the highest therapeutic potential, followed by psilocybin, and then alprazolam and methamphetamine. “Last was alcohol, which we expected because alcohol is not used therapeutically,” said Dr. Levin.

Survey completers viewed methamphetamine, alprazolam, and alcohol as having similarly high abuse potential, and ketamine as having mid-level abuse potential. Psilocybin was rated as having the lowest abuse potential, “which is exactly the opposite of what is implied by its schedule I status,” noted Dr. Levin.

The results provide evidence these drugs “are incorrectly scheduled,” he said.

“This suggests the schedule does not reflect current evidence, which I think is really important to understand because there are consequences to the drug schedule,” including criminal justice and research consequences, he added.

Dr. Levin pointed out that possession of drugs in more harmful schedules is linked to sometimes lengthy prison sentences.

The psychiatrists’ perceptions of the drugs “overlaps pretty significantly” with recent surveys of other mental health professionals, including psychologists and addiction experts, he noted.

The study was funded by the Drug Enforcement and Policy Center, Moritz College of Law, and The Ohio State University. Dr. Levin reported no relevant financial relationships.

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

Psychiatrists’ perceptions of the safety, therapeutic value, and abuse potential of psychoactive drugs are inconsistent with current drug policy, results from a new survey show.

“The consensus among experts, including psychiatrists, about specific drugs is not consistent or congruent with the schedule of these drugs” in the United States, lead author Adam Levin, MD, third-year psychiatry resident, Ohio State University, Columbus, and affiliate scholar at the Center for Psychedelic Drug Research and Education, Ohio State College of Social Work, told this news organization.

Dr. Levin stressed the importance of appropriate drug scheduling to improve access to treatments such as psilocybin (psychedelic mushrooms) and 4-methylenedioxy methamphetamine (MDMA), which are now being tested for psychiatric disorders.

“We are in the middle of a mental health crisis so having any new tools would be really important,” he said.

The survey findings were published online  in the International Journal of Drug Policy.
 

Five drug schedules

The Controlled Substances Act of 1970 created five “schedules” that organized drugs from most to least dangerous (schedule I-V). However, Dr. Levin said that the schedules do not accurately reflect the harms or therapeutic benefits of the various drugs.

Some drugs in lower, less restrictive schedules have greater potential for harm than do those in higher schedules, he noted. For example, methamphetamine, which has been recalled in multiple formulations because of concerns about abuse and limited medical use, remains a schedule II drug.

In addition, several schedule I drugs, including psilocybin and MDMA that are deemed dangerous and of no medical value, have shown therapeutic potential and low rates of misuse, addiction, or physical harm, the investigators noted.

In fact, the Food and Drug Administration has granted breakthrough therapy status to psilocybin for treatment-resistant depression and major depressive disorder (MDD) and to MDMA for posttraumatic stress disorder. This has positioned these drugs for possible FDA approval within the next few years.

Access to schedule I drugs for research purposes is tightly controlled. “Once psilocybin was placed in schedule I, there was this massive drop-off in the research funding and amount of research; and we’re just now starting to understand the potential therapeutic value of this drug,” said Dr. Levin.

Even with a recent research resurgence, most studies are funded by charitable donations or for-profit companies because of continued hesitancy on the part of grant-making organizations, he added.
 

Apparent contradictions

Given the pending approval of several schedule I drugs and escalating abuse of drugs in lower schedules, there is a growing need to understand physician attitudes surrounding the apparent contradictions in the drug schedule, the investigators noted.

Their survey included a geographically diverse group of 181 mostly middle-aged psychiatrists (65.2% were men) with an average of 16.2 years of practice after residency.

Participants were randomly assigned to respond to a vignette depicting a clinical scenario where a patient wants one of four drugs to help treat severe depression: psilocybin, a schedule I drug; methamphetamine (Desoxyn), a schedule II drug; ketamine, a Schedule III drug; or alprazolam (Xanax), a schedule IV drug.

Each of these therapies has established antidepressant properties, but none are FDA approved for treatment of MDD. However, an intranasal formulation of the ketamine enantiomer Spravato (esketamine) was recently approved for treatment-resistant depression.

There were significant differences among the groups presented with different vignettes. Participants were more likely to warn against repeated use of and development of a new psychiatric problem with methamphetamine and alprazolam compared with psilocybin or ketamine.

Respondents were most concerned about increased suicide risk after the nonprescribed use of alprazolam compared with psilocybin and ketamine.

Compared with all other drugs, ketamine was more likely to be integrated into treatment plans.
 

Therapeutic value, abuse potential

Participants were asked to rate the safety, therapeutic value, and abuse potential of the four drugs as well as alcohol, a nonscheduled legal drug, if used properly or as directed.

Respondents viewed psilocybin and ketamine as similarly safe – and safer than methamphetamine and alprazolam. They considered ketamine as having the highest therapeutic potential, followed by psilocybin, and then alprazolam and methamphetamine. “Last was alcohol, which we expected because alcohol is not used therapeutically,” said Dr. Levin.

Survey completers viewed methamphetamine, alprazolam, and alcohol as having similarly high abuse potential, and ketamine as having mid-level abuse potential. Psilocybin was rated as having the lowest abuse potential, “which is exactly the opposite of what is implied by its schedule I status,” noted Dr. Levin.

The results provide evidence these drugs “are incorrectly scheduled,” he said.

“This suggests the schedule does not reflect current evidence, which I think is really important to understand because there are consequences to the drug schedule,” including criminal justice and research consequences, he added.

Dr. Levin pointed out that possession of drugs in more harmful schedules is linked to sometimes lengthy prison sentences.

The psychiatrists’ perceptions of the drugs “overlaps pretty significantly” with recent surveys of other mental health professionals, including psychologists and addiction experts, he noted.

The study was funded by the Drug Enforcement and Policy Center, Moritz College of Law, and The Ohio State University. Dr. Levin reported no relevant financial relationships.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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