Conference Coverage

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

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

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

NEW ORLEANS – People with bipolar disorder – particularly men – show a significantly increased risk of osteoporosis, compared with the general population, but treatment with lithium appears to offer a significant protective effect against the bone disease, according to results from the largest study of its kind.

“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.

courtesy Aarhus University

For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.

Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.

With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).

The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).

Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.

Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
 

Results confirm prior research

The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.

The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.

“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”

While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.

In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.

“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.

The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.

“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”
 

Findings important for orthopedists

The unique properties observed with lithium have caught the attention of some in orthopedics, and researchers with the University of Toronto – having found intriguing bone healing with lithium in preclinical rodent studies – are currently conducting a first-of-its-kind multicenter, randomized, controlled clinical trial evaluating the potential effects of lithium in the healing of bone fractures.

courtesy Sunnybrook Health Sciences Centre

Diane Nam, MD, of the division of orthopedic surgery, Sunnybrook Health Sciences Centre, Toronto, and lead investigator on the study, said in an interview that “I’m not surprised by [Dr. Ostergaard’s] paper because it’s consistent with what we have observed about the positive effects on bone healing.”

Dr. Nam and associates have already established administration parameters for their clinical study, determining that optimal effects in fracture healing appear to require that lithium treatment not begin at the time of fracture, but 2 weeks afterward, when new bone is ready to be laid down at the fracture site. In their trial, low daily doses of lithium (at 300 mg) are given only for a duration of 2 weeks.

“While our current trial is intended for a healthy, nonosteoporotic adult population, we have also demonstrated in our preclinical studies that lithium is just as effective in improving fracture healing in an osteoporotic model when the timing of administration is slightly delayed,” she said. “How this is relevant and translatable in patients with bipolar disorder requires further study.”

Dr. Nam said her research team thinks that “not only will the fracture heal faster, but it will heal reliably as delayed or impaired fracture healing remains a significant orthopedic problem.”

While details are not yet available, a preliminary analysis has shown results “going in a positive direction,” enough for the team to be granted funding for the multicenter trial.

Dr. Ostergaard and Dr. Nam reported no disclosures or conflicts.

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

The use of adjunctive topical tranexamic acid (TXA) showed benefits in significantly reducing postoperative bleeding with second intention healing, or allowing wounds to heal naturally without sutures, following Mohs micrographic surgery, in a double-blind, randomized, controlled trial.

The findings suggest that “topical TXA application is an inexpensive and easy topical preventative measure to consider adding to the wound care of granulating defects in the setting of Mohs micrographic surgery,” first author Brianna Castillo, MD, chief dermatology resident at the University of Missouri, Columbia, told this news organization.

The study results were presented at the annual meeting of the American College of Mohs Surgery.

In wound healing by second intent after Mohs micrographic surgery, postoperative bleeding is common and can lead to patient distress, as well as return visits or emergency care, resulting in additional health care costs, Dr. Castillo said.

Topical TXA, an antifibrinolytic, synthetic lysine analogue that prevents blood clots from breaking down, is commonly used in surgical settings including cardiothoracic, orthopedic, gynecologic, oral, and trauma surgery, showing no increased risk of thrombotic events. However, its use is relatively new in dermatology.

TXA is approved by the Food and Drug Administration only as an oral formulation for menorrhagia in women and as a short-term preventative measure for hemophilia; however, other formulations are available for topical and subcutaneous uses, Dr. Castillo noted.

To evaluate the potential benefits of the treatment in postsurgical Mohs microsurgery bleeding, Dr. Castillo and colleagues enrolled 124 patients undergoing the surgery between October 2020 and December 2021 who had surgical defects deemed appropriate for second intention healing.

The patients were randomized to groups of 62 patients each to receive normal saline-soaked Telfa pads applied to the wound bed upon completion of surgery or TXA 25 mg/mL at a volume of 1 mL/cm²-soaked Telfa pads to the wound bed upon completion of the surgery.

In both groups, a standard pressure dressing was placed on top of the Telfa pads.

Most participants were men (90 vs. 34 patients), 45 were taking antiplatelet therapy, and 20 were taking anticoagulants, and in all cases, patients were similarly randomized in the two groups. Most of the surgical defects were on the head and neck or an extremity, and most (74) were under 2 cm.

All patients were provided with instructions to apply pressure to their wounds and to report bleeding complications. They were interviewed by phone 3 days following their surgeries regarding postoperative bleeding and any potential issues relating to the TXA treatment.

In follow-up interviews, six patients in the placebo group (9.7%) reported active bleeding from their wounds within 48 hours of surgery, with one patient requiring an intervention, while there were no reports of bleeding in the TXA group (P = .028). No side effects were reported in either group.

In the setting of Mohs micrographic surgery, subcutaneous TXA has previously been studied as an intraoperative hemostatic agent, with bleeding measured prior to the second layer or closure, Dr. Castillo explained. However, “no studies have evaluated topical TXA with the aim to reduce postoperative bleeding in the setting of Mohs micrographic surgery,” she said. 

Dr. Castillo noted that topical TXA is relatively inexpensive and typically available in hospital pharmacies. “It’s only about $7 per vial of 10 ccs and we do dilute it,” she noted during the session. “It has a pretty good shelf-life and does not have to be refrigerated.”

“We have implemented this into our practice at the University of Missouri,” she added.

Commenting on the study, M. Laurin Council, MD, associate professor of dermatology in the division of dermatology, department of internal medicine, Washington University, St. Louis, noted that second intention healing is “an excellent option for certain patients after skin cancer removal.

“One problem with this method, however, is that postsurgical wounds may bleed in the hours after a procedure, [and] this can be incredibly distressing to patients and their families,” she told this news organization.

“The study presented here shows great promise for the drug TXA for preventing postsurgical bleeding in this subset of patients,” said Dr. Council, director of dermatologic surgery and director of micrographic surgery and the dermatologic oncology fellowship at Washington University.

Commenting that “the results are impressive,” she noted the study had some limitations. “This is a small pilot study, and we don’t know about confounding factors in each group, such as the proportion of patients who are on blood thinners or who have low platelets, and therefore trouble clotting, for example.”

The authors have reported no relevant financial relationships. Dr. Council has consulted for AbbVie, Castle Biosciences, and Sanofi-Genzyme/Regeneron; however, the consulting was not relevant to the current study.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.