Every spring, I look forward to attending the American Psychiatric Association’s annual meeting. It has become a ritual that starts many months before the actual conference.

Submissions for presentations are due in September, so the planning often starts in the late summer. Hotel and plane reservations are made in January, and the meeting itself begins in May.

The city that hosts the event changes each year but, for me, many things do not. The Clinical Psychiatry News editorial board meeting takes place on Monday morning at 7 a.m., and I scour the program for what sessions to attend. In recent years, I have made a point of writing an article for about one of the sessions while still at the meeting – in 2019 I wrote about the improv-acting workshops I attended – something that just doesn’t translate to a Zoom experience.

I go with the same friend every year, I always attend the Hopkins alumni reception, and I organize dinner at a nice restaurant for friends. I have collected so many funny stories and memories over the years that it would be hard to catalog them all. There was the time in Toronto that I set up a meal at a restaurant named Susur – a meal like no other I’ve ever had – and the check arrived with a jaw-dropping sum that I had not anticipated. In San Diego, we watched a gorgeous sunset over the Pacific Ocean from the veranda of the Hotel Coronado. There was the time I sunbathed on the beach in Waikiki with my book editor, and the notable distress when my colleague’s husband called from the airport to say he was not permitted to board his plane in Baltimore to join us in California! There are funny stories, but there is the sadness that one friend who joined us for so many of these events has died.

I always find the program options to be overwhelming: There is so much going on at once that it can be hard to decide what to go to. I try to attend a mix of sessions, some that are inspiring or entertaining, and others that will be informative for clinical issues.

The speakers have been incredible and over the years I’ve heard then-Vice President Joseph Biden, retired quarterback Terry Bradshaw, Oliver Sacks, Alan Alda, Archbishop Desmond Tutu, and perhaps my favorite – Lorraine Bracco, the actress who played Dr. Melfi on “The Sopranos” – to name just a few. And, of course, the opportunity to get the continuing medical education credits I need for licensing is just one more reason to attend.

Last year in May I was still adjusting to my “new” career from home with a computer screen. I had been scheduled to participate in several panels for the meeting in Philadelphia, but extra computer hours had no appeal. And while the fatigue of doing telemental health has eased, I still avoid extra hours interacting with my computer screen and I did not attend this year’s meeting. Without the lure of friends, fun, and the novelty of being somewhere new, my APA experience would have to wait for real life.

Virtual APA has had a drop in participation. In 2019, the last real-life convention in San Francisco, there were 700 scientific sessions and 11,000 professionals in attendance. This year’s virtual conference hosted 135 sessions with more than 7,000 attendees. Attendance was down, but so were costs associated with live conventions and the APA is considering the addition of a virtual component when the annual meeting returns to the in-person venue.

Tom Abdallah is a medical student at Weill Cornell Medicine–Qatar in Education City. He has never attended an in-person APA annual meeting, but he joined for this year’s virtual sessions. “The scientific sessions were fantastic and diverse. Networking was limited in comparison to in-person conferences. The meeting was very well organized, and it gave me the opportunity to attend without worrying about travel.”

Steven Daviss, MD, a psychiatrist in Maryland, also commented on the ease and financial benefit of attending the meeting from his home office. He calculated that the cost was much less: $350 for virtual APA, compared with approximately $3,500 for the real thing, allowing for transportation, hotels, meals out, and lost income. “But,” said Dr. Daviss, “engagement with colleagues was minimal.”

APA Assembly member Annette Hanson, MD, has continued to go into work throughout the pandemic. Still, she noted that meetings and committee work have made sure she does not miss out on the “Zoom fatigue” that everyone else is feeling. The virtual APA was tiring for her.

“It was brutal. There was the APA Assembly 1 weekend, right after evening Zoom reference committee meetings the week before. Then virtual APA the next weekend. By the end of the week, I had worked every day for 3 weeks straight, including my more-than-full-time job!”

It has been a challenging time, to say the least, and it has certainly helped that videoconferencing has allowed us to be there for our patients and for each other in so many different circumstances. Former APA President Paul Summergrad, MD, talked about how virtual meetings can be very good as educational tools, but he conveyed what I have been feeling in a sentence: “I miss the social aspect of meetings.”

Please get your vaccine, and I hope to see you in New Orleans next May!

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Every spring, I look forward to attending the American Psychiatric Association’s annual meeting. It has become a ritual that starts many months before the actual conference.

Submissions for presentations are due in September, so the planning often starts in the late summer. Hotel and plane reservations are made in January, and the meeting itself begins in May.

The city that hosts the event changes each year but, for me, many things do not. The Clinical Psychiatry News editorial board meeting takes place on Monday morning at 7 a.m., and I scour the program for what sessions to attend. In recent years, I have made a point of writing an article for about one of the sessions while still at the meeting – in 2019 I wrote about the improv-acting workshops I attended – something that just doesn’t translate to a Zoom experience.

I go with the same friend every year, I always attend the Hopkins alumni reception, and I organize dinner at a nice restaurant for friends. I have collected so many funny stories and memories over the years that it would be hard to catalog them all. There was the time in Toronto that I set up a meal at a restaurant named Susur – a meal like no other I’ve ever had – and the check arrived with a jaw-dropping sum that I had not anticipated. In San Diego, we watched a gorgeous sunset over the Pacific Ocean from the veranda of the Hotel Coronado. There was the time I sunbathed on the beach in Waikiki with my book editor, and the notable distress when my colleague’s husband called from the airport to say he was not permitted to board his plane in Baltimore to join us in California! There are funny stories, but there is the sadness that one friend who joined us for so many of these events has died.

I always find the program options to be overwhelming: There is so much going on at once that it can be hard to decide what to go to. I try to attend a mix of sessions, some that are inspiring or entertaining, and others that will be informative for clinical issues.

The speakers have been incredible and over the years I’ve heard then-Vice President Joseph Biden, retired quarterback Terry Bradshaw, Oliver Sacks, Alan Alda, Archbishop Desmond Tutu, and perhaps my favorite – Lorraine Bracco, the actress who played Dr. Melfi on “The Sopranos” – to name just a few. And, of course, the opportunity to get the continuing medical education credits I need for licensing is just one more reason to attend.

Last year in May I was still adjusting to my “new” career from home with a computer screen. I had been scheduled to participate in several panels for the meeting in Philadelphia, but extra computer hours had no appeal. And while the fatigue of doing telemental health has eased, I still avoid extra hours interacting with my computer screen and I did not attend this year’s meeting. Without the lure of friends, fun, and the novelty of being somewhere new, my APA experience would have to wait for real life.

Virtual APA has had a drop in participation. In 2019, the last real-life convention in San Francisco, there were 700 scientific sessions and 11,000 professionals in attendance. This year’s virtual conference hosted 135 sessions with more than 7,000 attendees. Attendance was down, but so were costs associated with live conventions and the APA is considering the addition of a virtual component when the annual meeting returns to the in-person venue.

Tom Abdallah is a medical student at Weill Cornell Medicine–Qatar in Education City. He has never attended an in-person APA annual meeting, but he joined for this year’s virtual sessions. “The scientific sessions were fantastic and diverse. Networking was limited in comparison to in-person conferences. The meeting was very well organized, and it gave me the opportunity to attend without worrying about travel.”

Steven Daviss, MD, a psychiatrist in Maryland, also commented on the ease and financial benefit of attending the meeting from his home office. He calculated that the cost was much less: $350 for virtual APA, compared with approximately $3,500 for the real thing, allowing for transportation, hotels, meals out, and lost income. “But,” said Dr. Daviss, “engagement with colleagues was minimal.”

APA Assembly member Annette Hanson, MD, has continued to go into work throughout the pandemic. Still, she noted that meetings and committee work have made sure she does not miss out on the “Zoom fatigue” that everyone else is feeling. The virtual APA was tiring for her.

“It was brutal. There was the APA Assembly 1 weekend, right after evening Zoom reference committee meetings the week before. Then virtual APA the next weekend. By the end of the week, I had worked every day for 3 weeks straight, including my more-than-full-time job!”

It has been a challenging time, to say the least, and it has certainly helped that videoconferencing has allowed us to be there for our patients and for each other in so many different circumstances. Former APA President Paul Summergrad, MD, talked about how virtual meetings can be very good as educational tools, but he conveyed what I have been feeling in a sentence: “I miss the social aspect of meetings.”

Please get your vaccine, and I hope to see you in New Orleans next May!

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Every spring, I look forward to attending the American Psychiatric Association’s annual meeting. It has become a ritual that starts many months before the actual conference.

Submissions for presentations are due in September, so the planning often starts in the late summer. Hotel and plane reservations are made in January, and the meeting itself begins in May.

The city that hosts the event changes each year but, for me, many things do not. The Clinical Psychiatry News editorial board meeting takes place on Monday morning at 7 a.m., and I scour the program for what sessions to attend. In recent years, I have made a point of writing an article for about one of the sessions while still at the meeting – in 2019 I wrote about the improv-acting workshops I attended – something that just doesn’t translate to a Zoom experience.

I go with the same friend every year, I always attend the Hopkins alumni reception, and I organize dinner at a nice restaurant for friends. I have collected so many funny stories and memories over the years that it would be hard to catalog them all. There was the time in Toronto that I set up a meal at a restaurant named Susur – a meal like no other I’ve ever had – and the check arrived with a jaw-dropping sum that I had not anticipated. In San Diego, we watched a gorgeous sunset over the Pacific Ocean from the veranda of the Hotel Coronado. There was the time I sunbathed on the beach in Waikiki with my book editor, and the notable distress when my colleague’s husband called from the airport to say he was not permitted to board his plane in Baltimore to join us in California! There are funny stories, but there is the sadness that one friend who joined us for so many of these events has died.

I always find the program options to be overwhelming: There is so much going on at once that it can be hard to decide what to go to. I try to attend a mix of sessions, some that are inspiring or entertaining, and others that will be informative for clinical issues.

The speakers have been incredible and over the years I’ve heard then-Vice President Joseph Biden, retired quarterback Terry Bradshaw, Oliver Sacks, Alan Alda, Archbishop Desmond Tutu, and perhaps my favorite – Lorraine Bracco, the actress who played Dr. Melfi on “The Sopranos” – to name just a few. And, of course, the opportunity to get the continuing medical education credits I need for licensing is just one more reason to attend.

Last year in May I was still adjusting to my “new” career from home with a computer screen. I had been scheduled to participate in several panels for the meeting in Philadelphia, but extra computer hours had no appeal. And while the fatigue of doing telemental health has eased, I still avoid extra hours interacting with my computer screen and I did not attend this year’s meeting. Without the lure of friends, fun, and the novelty of being somewhere new, my APA experience would have to wait for real life.

Virtual APA has had a drop in participation. In 2019, the last real-life convention in San Francisco, there were 700 scientific sessions and 11,000 professionals in attendance. This year’s virtual conference hosted 135 sessions with more than 7,000 attendees. Attendance was down, but so were costs associated with live conventions and the APA is considering the addition of a virtual component when the annual meeting returns to the in-person venue.

Tom Abdallah is a medical student at Weill Cornell Medicine–Qatar in Education City. He has never attended an in-person APA annual meeting, but he joined for this year’s virtual sessions. “The scientific sessions were fantastic and diverse. Networking was limited in comparison to in-person conferences. The meeting was very well organized, and it gave me the opportunity to attend without worrying about travel.”

Steven Daviss, MD, a psychiatrist in Maryland, also commented on the ease and financial benefit of attending the meeting from his home office. He calculated that the cost was much less: $350 for virtual APA, compared with approximately $3,500 for the real thing, allowing for transportation, hotels, meals out, and lost income. “But,” said Dr. Daviss, “engagement with colleagues was minimal.”

APA Assembly member Annette Hanson, MD, has continued to go into work throughout the pandemic. Still, she noted that meetings and committee work have made sure she does not miss out on the “Zoom fatigue” that everyone else is feeling. The virtual APA was tiring for her.

“It was brutal. There was the APA Assembly 1 weekend, right after evening Zoom reference committee meetings the week before. Then virtual APA the next weekend. By the end of the week, I had worked every day for 3 weeks straight, including my more-than-full-time job!”

It has been a challenging time, to say the least, and it has certainly helped that videoconferencing has allowed us to be there for our patients and for each other in so many different circumstances. Former APA President Paul Summergrad, MD, talked about how virtual meetings can be very good as educational tools, but he conveyed what I have been feeling in a sentence: “I miss the social aspect of meetings.”

Please get your vaccine, and I hope to see you in New Orleans next May!

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

A plant-based fusion protein is safe and effective for inducing favorable immune modulation in patients with mild to moderate ulcerative colitis with no immune suppression–side effects reported.

OPRX-106, an orally administered BY2 plant cell–expressing recombinant TNF fusion protein, has demonstrated effectiveness as an anti–TNF-alpha therapy, according to Einat Almon, PhD, of Protalix Biotherapeutics, and colleagues.

“Oral immune therapy is based on the concept of oral administration of nonabsorbable compounds which target the gut immune system to redirect the systemic immune system toward an anti-inflammatory direction, without immunosuppression,” the researchers said.

A phase 1 study of OPRX-106 in healthy human volunteers showed safety and immune modulatory effects at doses of 2, 8, or 16 mg/day.

In this phase 2a clinical trial published in the Journal of Clinical Gastroenterology, the researchers enrolled 24 patients with ulcerative colitis (11 male and 13 female) aged 23-73 years, with an average age of 42.6 years. Patients received either 2 mg or 8 mg of OPRX-106 at least once daily for 8 weeks. All patients were monitored for 6 hours after receiving medication on day 1 and week 8 for pharmacokinetic sampling, and a lower endoscopy was performed at week 8.

After 8 weeks, 67% of the patients demonstrated clinical response and 28% showed clinical remission.

Clinical response and clinical remission were defined by a specific set of criteria including improvement in the Mayo score. Clinical response was a “decrease in the Mayo score of at least 3 points, decrease in the subscore for rectal bleeding of at least 1 point, [and] a rectal bleeding subscore of 0 or 1.” Clinical remission at week 8 was defined as “clinically symptom-free, Mayo score of ≤2 with no individual subscore exceeding 1 point after treatment, histopathological improvement in Geboes histologic grading from baseline to week 8, improvement in high sensitivity C-reactive protein levels from baseline to week 8, improvement in fecal calprotectin levels from baseline to week 8, and changes in systemic immune modulation parameters from baseline to week 8.”

In addition, 89% of the patients experienced some degree of improvement in their Mayo scores, 61% had mucosal improvement, and 33% achieved mucosal healing.

No side effects associated with general immune suppression were reported. No patients discontinued the study because of adverse events, the researchers said. However, overall, 40 adverse events were reported in 15 patients; 95% of these were mild to moderate and 40% were reported as treatment related. No differences appeared in adverse events related to the two doses.

Evidence of a systemic anti-inflammatory effect was seen with a decrease in serum levels of the pro-inflammatory cytokines interleukin-6 and interferon-gamma that correlated with the clinical response, the researchers noted. Similarly, an increase in the CD3+CD4+CD25+Foxp3+ subset of suppressor lymphocytes correlated with clinical response.

The study findings were limited by the small sample size, open-label design, and lack of control subjects. However, by targeting the gut immune system, the drug “may provide an answer to the long-term immune suppression encountered in patients with chronic disorders who use these agents for prolonged periods of time, in addition to loss of response due to neutralizing antibodies,” they concluded.
 

Findings provide foundation for further research

“Conducting a study of a novel treatment for ulcerative colitis is valuable and timely because the available options are limited,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview. “The currently available TNF antagonists are administered intravenously or subcutaneously and bear the risk of infectious complications, so the development of an agent that can be administered orally with fewer side effects is of importance.”

Although the data are preliminary, Dr. Sakuraba emphasized that the take-home message for clinicians is that “the present open-label study consisting of a small number of subjects demonstrated that OPRX-106 was effective and safe in active ulcerative colitis, so further investigation is warranted. Larger-powered, randomized, placebo-controlled studies are needed to confirm these findings.”

The study was supported by Protalix Biotherapeutics; Dr. Almon and several coauthors are employed by Protalix Biotherapeutics. Dr. Sakuraba had no financial conflicts to disclose.

A plant-based fusion protein is safe and effective for inducing favorable immune modulation in patients with mild to moderate ulcerative colitis with no immune suppression–side effects reported.

OPRX-106, an orally administered BY2 plant cell–expressing recombinant TNF fusion protein, has demonstrated effectiveness as an anti–TNF-alpha therapy, according to Einat Almon, PhD, of Protalix Biotherapeutics, and colleagues.

“Oral immune therapy is based on the concept of oral administration of nonabsorbable compounds which target the gut immune system to redirect the systemic immune system toward an anti-inflammatory direction, without immunosuppression,” the researchers said.

A phase 1 study of OPRX-106 in healthy human volunteers showed safety and immune modulatory effects at doses of 2, 8, or 16 mg/day.

In this phase 2a clinical trial published in the Journal of Clinical Gastroenterology, the researchers enrolled 24 patients with ulcerative colitis (11 male and 13 female) aged 23-73 years, with an average age of 42.6 years. Patients received either 2 mg or 8 mg of OPRX-106 at least once daily for 8 weeks. All patients were monitored for 6 hours after receiving medication on day 1 and week 8 for pharmacokinetic sampling, and a lower endoscopy was performed at week 8.

After 8 weeks, 67% of the patients demonstrated clinical response and 28% showed clinical remission.

Clinical response and clinical remission were defined by a specific set of criteria including improvement in the Mayo score. Clinical response was a “decrease in the Mayo score of at least 3 points, decrease in the subscore for rectal bleeding of at least 1 point, [and] a rectal bleeding subscore of 0 or 1.” Clinical remission at week 8 was defined as “clinically symptom-free, Mayo score of ≤2 with no individual subscore exceeding 1 point after treatment, histopathological improvement in Geboes histologic grading from baseline to week 8, improvement in high sensitivity C-reactive protein levels from baseline to week 8, improvement in fecal calprotectin levels from baseline to week 8, and changes in systemic immune modulation parameters from baseline to week 8.”

In addition, 89% of the patients experienced some degree of improvement in their Mayo scores, 61% had mucosal improvement, and 33% achieved mucosal healing.

No side effects associated with general immune suppression were reported. No patients discontinued the study because of adverse events, the researchers said. However, overall, 40 adverse events were reported in 15 patients; 95% of these were mild to moderate and 40% were reported as treatment related. No differences appeared in adverse events related to the two doses.

Evidence of a systemic anti-inflammatory effect was seen with a decrease in serum levels of the pro-inflammatory cytokines interleukin-6 and interferon-gamma that correlated with the clinical response, the researchers noted. Similarly, an increase in the CD3+CD4+CD25+Foxp3+ subset of suppressor lymphocytes correlated with clinical response.

The study findings were limited by the small sample size, open-label design, and lack of control subjects. However, by targeting the gut immune system, the drug “may provide an answer to the long-term immune suppression encountered in patients with chronic disorders who use these agents for prolonged periods of time, in addition to loss of response due to neutralizing antibodies,” they concluded.
 

Findings provide foundation for further research

“Conducting a study of a novel treatment for ulcerative colitis is valuable and timely because the available options are limited,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview. “The currently available TNF antagonists are administered intravenously or subcutaneously and bear the risk of infectious complications, so the development of an agent that can be administered orally with fewer side effects is of importance.”

Although the data are preliminary, Dr. Sakuraba emphasized that the take-home message for clinicians is that “the present open-label study consisting of a small number of subjects demonstrated that OPRX-106 was effective and safe in active ulcerative colitis, so further investigation is warranted. Larger-powered, randomized, placebo-controlled studies are needed to confirm these findings.”

The study was supported by Protalix Biotherapeutics; Dr. Almon and several coauthors are employed by Protalix Biotherapeutics. Dr. Sakuraba had no financial conflicts to disclose.

A plant-based fusion protein is safe and effective for inducing favorable immune modulation in patients with mild to moderate ulcerative colitis with no immune suppression–side effects reported.

OPRX-106, an orally administered BY2 plant cell–expressing recombinant TNF fusion protein, has demonstrated effectiveness as an anti–TNF-alpha therapy, according to Einat Almon, PhD, of Protalix Biotherapeutics, and colleagues.

“Oral immune therapy is based on the concept of oral administration of nonabsorbable compounds which target the gut immune system to redirect the systemic immune system toward an anti-inflammatory direction, without immunosuppression,” the researchers said.

A phase 1 study of OPRX-106 in healthy human volunteers showed safety and immune modulatory effects at doses of 2, 8, or 16 mg/day.

In this phase 2a clinical trial published in the Journal of Clinical Gastroenterology, the researchers enrolled 24 patients with ulcerative colitis (11 male and 13 female) aged 23-73 years, with an average age of 42.6 years. Patients received either 2 mg or 8 mg of OPRX-106 at least once daily for 8 weeks. All patients were monitored for 6 hours after receiving medication on day 1 and week 8 for pharmacokinetic sampling, and a lower endoscopy was performed at week 8.

After 8 weeks, 67% of the patients demonstrated clinical response and 28% showed clinical remission.

Clinical response and clinical remission were defined by a specific set of criteria including improvement in the Mayo score. Clinical response was a “decrease in the Mayo score of at least 3 points, decrease in the subscore for rectal bleeding of at least 1 point, [and] a rectal bleeding subscore of 0 or 1.” Clinical remission at week 8 was defined as “clinically symptom-free, Mayo score of ≤2 with no individual subscore exceeding 1 point after treatment, histopathological improvement in Geboes histologic grading from baseline to week 8, improvement in high sensitivity C-reactive protein levels from baseline to week 8, improvement in fecal calprotectin levels from baseline to week 8, and changes in systemic immune modulation parameters from baseline to week 8.”

In addition, 89% of the patients experienced some degree of improvement in their Mayo scores, 61% had mucosal improvement, and 33% achieved mucosal healing.

No side effects associated with general immune suppression were reported. No patients discontinued the study because of adverse events, the researchers said. However, overall, 40 adverse events were reported in 15 patients; 95% of these were mild to moderate and 40% were reported as treatment related. No differences appeared in adverse events related to the two doses.

Evidence of a systemic anti-inflammatory effect was seen with a decrease in serum levels of the pro-inflammatory cytokines interleukin-6 and interferon-gamma that correlated with the clinical response, the researchers noted. Similarly, an increase in the CD3+CD4+CD25+Foxp3+ subset of suppressor lymphocytes correlated with clinical response.

The study findings were limited by the small sample size, open-label design, and lack of control subjects. However, by targeting the gut immune system, the drug “may provide an answer to the long-term immune suppression encountered in patients with chronic disorders who use these agents for prolonged periods of time, in addition to loss of response due to neutralizing antibodies,” they concluded.
 

Findings provide foundation for further research

“Conducting a study of a novel treatment for ulcerative colitis is valuable and timely because the available options are limited,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview. “The currently available TNF antagonists are administered intravenously or subcutaneously and bear the risk of infectious complications, so the development of an agent that can be administered orally with fewer side effects is of importance.”

Although the data are preliminary, Dr. Sakuraba emphasized that the take-home message for clinicians is that “the present open-label study consisting of a small number of subjects demonstrated that OPRX-106 was effective and safe in active ulcerative colitis, so further investigation is warranted. Larger-powered, randomized, placebo-controlled studies are needed to confirm these findings.”

The study was supported by Protalix Biotherapeutics; Dr. Almon and several coauthors are employed by Protalix Biotherapeutics. Dr. Sakuraba had no financial conflicts to disclose.

Click here for the Friday issue of the SHM Converge Daily News newsletter.

Click here for the Friday issue of the SHM Converge Daily News newsletter.

Click here for the Friday issue of the SHM Converge Daily News newsletter.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

While the COVID-19 pandemic has generated anxiety and confusion in medicine, one thing should bring a sense of clarity to hospitalists: They’re needed now more than ever.

Larry Wellikson, MD, MHM, the former, longtime CEO of the Society of Hospital Medicine, in a May 6 keynote speech at SHM Converge, the annual conference of the Society of Hospital Medicine, said the COVID-19 era has underscored the singular importance of the specialty.

“I think one thing that this recent pandemic has emphasized is just how important and vital hospitalists are to the United States’ health care system,” Dr. Wellikson said. “The response to the acute care needs in this pandemic would have been impossible in the health care system that existed before hospitalists. And so this is something that we should understand and appreciate.”

The “upheaval” experienced in hospital medicine continues a trend of change that will go on, both in the corporate health care landscape and in the role that hospitalists play in providing care, he said. Insurers have been merging and looking to consolidate. Hospital medicine companies have been merging, and “newfangled bedfellows” have been a trend, such as CVS stepping beyond its pharmacy role into an expanded health care role, Cigna buying Express Scripts, and an Amazon-Berkshire Hathaway-J.P. Morgan health care partnership that ultimately did not pan out, although that hasn’t ended Amazon’s presence in health care.

“You may not realize it, but Amazon is currently one of the largest hospital supply-chain companies,” Dr. Wellikson said. “They’re attempting to become a major pharmacy benefits manager and will only further enter into health care and into our personal and professional lives.”

New models of care point to the way of the future, he said. Mount Sinai’s continuing success with its Hospital at Home program – which involves an acute care nurse and team assigned to a patient in the home – introduces a concept that will be adopted more broadly, because of its cost savings and good outcomes, he said. Mergers of hospital systems, leading to excess hospital capacity, has given rise to what he calls “ED-plus,” or using formerly full-service hospitals as more focused centers – providing emergency, obstetrician, cardiology, x-ray, or orthopedics care, or whatever is needed in a given community.

An increasing focus on population health rather than procedures plays into the strengths of hospitalists, Dr. Wellikson said, and the need for their skills will continue to deepen.

When changes in reimbursement began about 4 years ago, specialties such as cardiology entered into new contracts with hospitals, but the facilities began to notice that many of the services – such as initial heart failure and chest pain management – can be provided by hospitalists.

“They’re signing fewer cardiologists and needing therefore to hire more hospitalists,” he said.

To keep readmissions low and subsequent costs down, hospitalists will continue to handle the first few postdischarge visits with patients, he said. This is crucial in bundled payment systems.

“Most of the savings in those systems comes from being very efficient in the initial postdischarge portion of people’s care,” Dr. Wellikson said.

At the same time, hospitalists are not in “unlimited supply.”

“I think every hospital medicine group should be assessing and working on improving their clinicians’ well-being,” he said. “We need to ration somewhat, so we’re deploying hospitalists for the things that only we can do.” He predicted that hospitalists will be required to work in the electronic medical record less frequently, with this task handled by others.

Dr. Wellikson also called on the specialty to continue to expand its racial and ethnic diversity so that it reflects the patient population it serves.

“We’re looking to create pathways to leadership for everyone and not just a tokenism moving forward,” he said.

The basic strengths of hospital medicine – its flexibility, professional culture, and youth – leave it well prepared for all of these changes, he said.

“There is a bright future and hospitalists are right in the middle of this – we’re not going to be marginalized or on the periphery,” Dr. Wellikson said. “If I had one message for all of you, I would say be relevant and add value and you will not only survive, but thrive.”
 

RIV winners announced

The winners of the 2021 RIV competition were also announced at the May 6 general session of Converge. There were two winners in each of the three categories, as follows:

RESEARCH
Overall: “Suboptimal Communication During Inter-Hospital Transfer,” Stephanie Mueller, MD, MPH, SFHM

Trainee: “Mentorship in Pediatric Hospital Medicine: A Survey of Division Directors,” Brandon Palmer, MD

INNOVATIONS
Overall: “Leveraging Artificial Intelligence for a Team-Based Approach to Advance Care Planning,” Ron Li, MD

Trainee: “A Trainee-Designed Initiative Reshapes Communication for Hospital Medicine Patients During COVID-19,” Smitha Ganeshan, MD, MBA

CLINICAL VIGNETTES
Adults: “Holy Spontaneous Heparin-Induced Thrombocytopenia,” Min Hwang

Pediatrics: “The Great Pretender: A Tale of Two Systems,” Shivani Desai, MD

While the COVID-19 pandemic has generated anxiety and confusion in medicine, one thing should bring a sense of clarity to hospitalists: They’re needed now more than ever.

Larry Wellikson, MD, MHM, the former, longtime CEO of the Society of Hospital Medicine, in a May 6 keynote speech at SHM Converge, the annual conference of the Society of Hospital Medicine, said the COVID-19 era has underscored the singular importance of the specialty.

“I think one thing that this recent pandemic has emphasized is just how important and vital hospitalists are to the United States’ health care system,” Dr. Wellikson said. “The response to the acute care needs in this pandemic would have been impossible in the health care system that existed before hospitalists. And so this is something that we should understand and appreciate.”

The “upheaval” experienced in hospital medicine continues a trend of change that will go on, both in the corporate health care landscape and in the role that hospitalists play in providing care, he said. Insurers have been merging and looking to consolidate. Hospital medicine companies have been merging, and “newfangled bedfellows” have been a trend, such as CVS stepping beyond its pharmacy role into an expanded health care role, Cigna buying Express Scripts, and an Amazon-Berkshire Hathaway-J.P. Morgan health care partnership that ultimately did not pan out, although that hasn’t ended Amazon’s presence in health care.

“You may not realize it, but Amazon is currently one of the largest hospital supply-chain companies,” Dr. Wellikson said. “They’re attempting to become a major pharmacy benefits manager and will only further enter into health care and into our personal and professional lives.”

New models of care point to the way of the future, he said. Mount Sinai’s continuing success with its Hospital at Home program – which involves an acute care nurse and team assigned to a patient in the home – introduces a concept that will be adopted more broadly, because of its cost savings and good outcomes, he said. Mergers of hospital systems, leading to excess hospital capacity, has given rise to what he calls “ED-plus,” or using formerly full-service hospitals as more focused centers – providing emergency, obstetrician, cardiology, x-ray, or orthopedics care, or whatever is needed in a given community.

An increasing focus on population health rather than procedures plays into the strengths of hospitalists, Dr. Wellikson said, and the need for their skills will continue to deepen.

When changes in reimbursement began about 4 years ago, specialties such as cardiology entered into new contracts with hospitals, but the facilities began to notice that many of the services – such as initial heart failure and chest pain management – can be provided by hospitalists.

“They’re signing fewer cardiologists and needing therefore to hire more hospitalists,” he said.

To keep readmissions low and subsequent costs down, hospitalists will continue to handle the first few postdischarge visits with patients, he said. This is crucial in bundled payment systems.

“Most of the savings in those systems comes from being very efficient in the initial postdischarge portion of people’s care,” Dr. Wellikson said.

At the same time, hospitalists are not in “unlimited supply.”

“I think every hospital medicine group should be assessing and working on improving their clinicians’ well-being,” he said. “We need to ration somewhat, so we’re deploying hospitalists for the things that only we can do.” He predicted that hospitalists will be required to work in the electronic medical record less frequently, with this task handled by others.

Dr. Wellikson also called on the specialty to continue to expand its racial and ethnic diversity so that it reflects the patient population it serves.

“We’re looking to create pathways to leadership for everyone and not just a tokenism moving forward,” he said.

The basic strengths of hospital medicine – its flexibility, professional culture, and youth – leave it well prepared for all of these changes, he said.

“There is a bright future and hospitalists are right in the middle of this – we’re not going to be marginalized or on the periphery,” Dr. Wellikson said. “If I had one message for all of you, I would say be relevant and add value and you will not only survive, but thrive.”
 

RIV winners announced

The winners of the 2021 RIV competition were also announced at the May 6 general session of Converge. There were two winners in each of the three categories, as follows:

RESEARCH
Overall: “Suboptimal Communication During Inter-Hospital Transfer,” Stephanie Mueller, MD, MPH, SFHM

Trainee: “Mentorship in Pediatric Hospital Medicine: A Survey of Division Directors,” Brandon Palmer, MD

INNOVATIONS
Overall: “Leveraging Artificial Intelligence for a Team-Based Approach to Advance Care Planning,” Ron Li, MD

Trainee: “A Trainee-Designed Initiative Reshapes Communication for Hospital Medicine Patients During COVID-19,” Smitha Ganeshan, MD, MBA

CLINICAL VIGNETTES
Adults: “Holy Spontaneous Heparin-Induced Thrombocytopenia,” Min Hwang

Pediatrics: “The Great Pretender: A Tale of Two Systems,” Shivani Desai, MD

While the COVID-19 pandemic has generated anxiety and confusion in medicine, one thing should bring a sense of clarity to hospitalists: They’re needed now more than ever.

Larry Wellikson, MD, MHM, the former, longtime CEO of the Society of Hospital Medicine, in a May 6 keynote speech at SHM Converge, the annual conference of the Society of Hospital Medicine, said the COVID-19 era has underscored the singular importance of the specialty.

“I think one thing that this recent pandemic has emphasized is just how important and vital hospitalists are to the United States’ health care system,” Dr. Wellikson said. “The response to the acute care needs in this pandemic would have been impossible in the health care system that existed before hospitalists. And so this is something that we should understand and appreciate.”

The “upheaval” experienced in hospital medicine continues a trend of change that will go on, both in the corporate health care landscape and in the role that hospitalists play in providing care, he said. Insurers have been merging and looking to consolidate. Hospital medicine companies have been merging, and “newfangled bedfellows” have been a trend, such as CVS stepping beyond its pharmacy role into an expanded health care role, Cigna buying Express Scripts, and an Amazon-Berkshire Hathaway-J.P. Morgan health care partnership that ultimately did not pan out, although that hasn’t ended Amazon’s presence in health care.

“You may not realize it, but Amazon is currently one of the largest hospital supply-chain companies,” Dr. Wellikson said. “They’re attempting to become a major pharmacy benefits manager and will only further enter into health care and into our personal and professional lives.”

New models of care point to the way of the future, he said. Mount Sinai’s continuing success with its Hospital at Home program – which involves an acute care nurse and team assigned to a patient in the home – introduces a concept that will be adopted more broadly, because of its cost savings and good outcomes, he said. Mergers of hospital systems, leading to excess hospital capacity, has given rise to what he calls “ED-plus,” or using formerly full-service hospitals as more focused centers – providing emergency, obstetrician, cardiology, x-ray, or orthopedics care, or whatever is needed in a given community.

An increasing focus on population health rather than procedures plays into the strengths of hospitalists, Dr. Wellikson said, and the need for their skills will continue to deepen.

When changes in reimbursement began about 4 years ago, specialties such as cardiology entered into new contracts with hospitals, but the facilities began to notice that many of the services – such as initial heart failure and chest pain management – can be provided by hospitalists.

“They’re signing fewer cardiologists and needing therefore to hire more hospitalists,” he said.

To keep readmissions low and subsequent costs down, hospitalists will continue to handle the first few postdischarge visits with patients, he said. This is crucial in bundled payment systems.

“Most of the savings in those systems comes from being very efficient in the initial postdischarge portion of people’s care,” Dr. Wellikson said.

At the same time, hospitalists are not in “unlimited supply.”

“I think every hospital medicine group should be assessing and working on improving their clinicians’ well-being,” he said. “We need to ration somewhat, so we’re deploying hospitalists for the things that only we can do.” He predicted that hospitalists will be required to work in the electronic medical record less frequently, with this task handled by others.

Dr. Wellikson also called on the specialty to continue to expand its racial and ethnic diversity so that it reflects the patient population it serves.

“We’re looking to create pathways to leadership for everyone and not just a tokenism moving forward,” he said.

The basic strengths of hospital medicine – its flexibility, professional culture, and youth – leave it well prepared for all of these changes, he said.

“There is a bright future and hospitalists are right in the middle of this – we’re not going to be marginalized or on the periphery,” Dr. Wellikson said. “If I had one message for all of you, I would say be relevant and add value and you will not only survive, but thrive.”
 

RIV winners announced

The winners of the 2021 RIV competition were also announced at the May 6 general session of Converge. There were two winners in each of the three categories, as follows:

RESEARCH
Overall: “Suboptimal Communication During Inter-Hospital Transfer,” Stephanie Mueller, MD, MPH, SFHM

Trainee: “Mentorship in Pediatric Hospital Medicine: A Survey of Division Directors,” Brandon Palmer, MD

INNOVATIONS
Overall: “Leveraging Artificial Intelligence for a Team-Based Approach to Advance Care Planning,” Ron Li, MD

Trainee: “A Trainee-Designed Initiative Reshapes Communication for Hospital Medicine Patients During COVID-19,” Smitha Ganeshan, MD, MBA

CLINICAL VIGNETTES
Adults: “Holy Spontaneous Heparin-Induced Thrombocytopenia,” Min Hwang

Pediatrics: “The Great Pretender: A Tale of Two Systems,” Shivani Desai, MD

Asking a patient who has concerns about memory loss–particular questions can guide referral decisions, according to new research.

Initial questions should zero in on what the patient is forgetting, said Megan Richie, MD, a neurohospitalist at the University of California, San Francisco, who spoke to a virtual audience at the American College of Physicians (ACP) annual Internal Medicine meeting.

Is the patient forgetting to buy things in a store, having trouble recalling events, forgetting important dates? How often do these incidents occur?

These questions “will help get at how pervasive and how likely the memory loss is affecting their lives, versus a subjective complaint that doesn’t have much impact on the day-to-day function,” she said.

It’s also important to ask whether other neurocognitive symptoms accompany the memory loss, Dr. Richie noted.

Does the patient search for words, struggle with attention, or have problems with executive function? Does the patient have psychiatric symptoms, such as hallucinations or delusions, or other neurologic complaints, including weakness, numbness, vision change, or movement disorders?

“When you know how many neurocognitive symptoms they have, think about how [those symptoms] are affecting their safety and functional status. How are they on their activities of daily living?” Dr. Richie suggests.

Also ask whether the patient is taking medications and whether they drive a vehicle. If they do drive, do they get lost?

“These are all going to help you determine the acuity of the workup,” she said.

After a thorough history, cognitive screening is the next consideration.
 

Cognitive screening can be performed in minutes

One of the tests Dr. Richie recommends is the Mini-Cog. It takes 3 minutes to administer and has been formally recommended by the Alzheimer’s Association because it can be completed in the time frame of a Medicare wellness visit, she said.

It entails a three-word recall and clock-drawing test.

Dr. Richie said it’s important to eliminate some key causes first: “Certainly if the patient has signs and symptoms of depression, pseudodementia is a very real and treatable disease you do not want to miss and should consider in these patients,” she pointed out.

Systemic medical conditions can also lead to memory loss.

If there’s an acute component to the complaint, a new infection or medication withdrawal or a side effect could be driving it, so that’s key in questioning.

Dr. Richie explained that the American Academy of Neurology recommends a very limited workup.

“It’s really just to check their thyroid, their vitamin B12 levels, and then a one-time picture of their brain, which can be either MRI or a CT, to look for structural problems or vascular dementia or hydrocephalus, etc.”

“You do not routinely need spinal fluid testing or an EEG,” she emphasized.

Signs that a neurologist should be involved include a rapid decline, signs of potential seizures, or that the patient doesn’t seem safe in their condition.

Neuropsychological testing is helpful, but it takes nearly 3 hours and may not be a good choice for restless or aggressive patients, Dr. Richie said.

Such testing is often not available, and if it is, insurance coverage is often a barrier because many plans don’t cover it.

Patients often ask about drugs and supplements they see advertised to help with memory loss. Medications are not helpful for mild cognitive impairment, although there is evidence that some are beneficial for patients with dementia, Dr. Richie said.

Celine Goetz, MD, assistant professor of internal medicine at Rush University Medical Center, Chicago, Illinois, told this news organization that it’s easy to relate to the fear that patients and families feel when cognitive impairment begins to emerge.

“[Dr.] Richie’s talk was right on point for internists like myself who see many patients with memory complaints, cognitive impairment, and dementia. I think we’re all terrified of losing our memory and the social and functional impairment that comes with that,” she said.

Although cognitive impairment and dementia aren’t curable or reversible, Dr. Goetz noted, internists can help patients optimize management of conditions such as diabetes and heart disease, which can affect cognitive function.

Dr. Richie pointed out that some interventions lack evidence for the treatment of mild cognitive impairment, but Dr. Goetz emphasized that resources are plentiful and can be effective in combination.

“Engaging social workers, pharmacists, nutritionists, physical and occupational therapists, and, on the inpatient side, delirium protocols, chaplains, and music therapists make a huge difference in patient care,” she said.

Dr. Richie and Dr. Goetz report no relevant financial relationships.

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

Asking a patient who has concerns about memory loss–particular questions can guide referral decisions, according to new research.

Initial questions should zero in on what the patient is forgetting, said Megan Richie, MD, a neurohospitalist at the University of California, San Francisco, who spoke to a virtual audience at the American College of Physicians (ACP) annual Internal Medicine meeting.

Is the patient forgetting to buy things in a store, having trouble recalling events, forgetting important dates? How often do these incidents occur?

These questions “will help get at how pervasive and how likely the memory loss is affecting their lives, versus a subjective complaint that doesn’t have much impact on the day-to-day function,” she said.

It’s also important to ask whether other neurocognitive symptoms accompany the memory loss, Dr. Richie noted.

Does the patient search for words, struggle with attention, or have problems with executive function? Does the patient have psychiatric symptoms, such as hallucinations or delusions, or other neurologic complaints, including weakness, numbness, vision change, or movement disorders?

“When you know how many neurocognitive symptoms they have, think about how [those symptoms] are affecting their safety and functional status. How are they on their activities of daily living?” Dr. Richie suggests.

Also ask whether the patient is taking medications and whether they drive a vehicle. If they do drive, do they get lost?

“These are all going to help you determine the acuity of the workup,” she said.

After a thorough history, cognitive screening is the next consideration.
 

Cognitive screening can be performed in minutes

One of the tests Dr. Richie recommends is the Mini-Cog. It takes 3 minutes to administer and has been formally recommended by the Alzheimer’s Association because it can be completed in the time frame of a Medicare wellness visit, she said.

It entails a three-word recall and clock-drawing test.

Dr. Richie said it’s important to eliminate some key causes first: “Certainly if the patient has signs and symptoms of depression, pseudodementia is a very real and treatable disease you do not want to miss and should consider in these patients,” she pointed out.

Systemic medical conditions can also lead to memory loss.

If there’s an acute component to the complaint, a new infection or medication withdrawal or a side effect could be driving it, so that’s key in questioning.

Dr. Richie explained that the American Academy of Neurology recommends a very limited workup.

“It’s really just to check their thyroid, their vitamin B12 levels, and then a one-time picture of their brain, which can be either MRI or a CT, to look for structural problems or vascular dementia or hydrocephalus, etc.”

“You do not routinely need spinal fluid testing or an EEG,” she emphasized.

Signs that a neurologist should be involved include a rapid decline, signs of potential seizures, or that the patient doesn’t seem safe in their condition.

Neuropsychological testing is helpful, but it takes nearly 3 hours and may not be a good choice for restless or aggressive patients, Dr. Richie said.

Such testing is often not available, and if it is, insurance coverage is often a barrier because many plans don’t cover it.

Patients often ask about drugs and supplements they see advertised to help with memory loss. Medications are not helpful for mild cognitive impairment, although there is evidence that some are beneficial for patients with dementia, Dr. Richie said.

Celine Goetz, MD, assistant professor of internal medicine at Rush University Medical Center, Chicago, Illinois, told this news organization that it’s easy to relate to the fear that patients and families feel when cognitive impairment begins to emerge.

“[Dr.] Richie’s talk was right on point for internists like myself who see many patients with memory complaints, cognitive impairment, and dementia. I think we’re all terrified of losing our memory and the social and functional impairment that comes with that,” she said.

Although cognitive impairment and dementia aren’t curable or reversible, Dr. Goetz noted, internists can help patients optimize management of conditions such as diabetes and heart disease, which can affect cognitive function.

Dr. Richie pointed out that some interventions lack evidence for the treatment of mild cognitive impairment, but Dr. Goetz emphasized that resources are plentiful and can be effective in combination.

“Engaging social workers, pharmacists, nutritionists, physical and occupational therapists, and, on the inpatient side, delirium protocols, chaplains, and music therapists make a huge difference in patient care,” she said.

Dr. Richie and Dr. Goetz report no relevant financial relationships.

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

Asking a patient who has concerns about memory loss–particular questions can guide referral decisions, according to new research.

Initial questions should zero in on what the patient is forgetting, said Megan Richie, MD, a neurohospitalist at the University of California, San Francisco, who spoke to a virtual audience at the American College of Physicians (ACP) annual Internal Medicine meeting.

Is the patient forgetting to buy things in a store, having trouble recalling events, forgetting important dates? How often do these incidents occur?

These questions “will help get at how pervasive and how likely the memory loss is affecting their lives, versus a subjective complaint that doesn’t have much impact on the day-to-day function,” she said.

It’s also important to ask whether other neurocognitive symptoms accompany the memory loss, Dr. Richie noted.

Does the patient search for words, struggle with attention, or have problems with executive function? Does the patient have psychiatric symptoms, such as hallucinations or delusions, or other neurologic complaints, including weakness, numbness, vision change, or movement disorders?

“When you know how many neurocognitive symptoms they have, think about how [those symptoms] are affecting their safety and functional status. How are they on their activities of daily living?” Dr. Richie suggests.

Also ask whether the patient is taking medications and whether they drive a vehicle. If they do drive, do they get lost?

“These are all going to help you determine the acuity of the workup,” she said.

After a thorough history, cognitive screening is the next consideration.
 

Cognitive screening can be performed in minutes

One of the tests Dr. Richie recommends is the Mini-Cog. It takes 3 minutes to administer and has been formally recommended by the Alzheimer’s Association because it can be completed in the time frame of a Medicare wellness visit, she said.

It entails a three-word recall and clock-drawing test.

Dr. Richie said it’s important to eliminate some key causes first: “Certainly if the patient has signs and symptoms of depression, pseudodementia is a very real and treatable disease you do not want to miss and should consider in these patients,” she pointed out.

Systemic medical conditions can also lead to memory loss.

If there’s an acute component to the complaint, a new infection or medication withdrawal or a side effect could be driving it, so that’s key in questioning.

Dr. Richie explained that the American Academy of Neurology recommends a very limited workup.

“It’s really just to check their thyroid, their vitamin B12 levels, and then a one-time picture of their brain, which can be either MRI or a CT, to look for structural problems or vascular dementia or hydrocephalus, etc.”

“You do not routinely need spinal fluid testing or an EEG,” she emphasized.

Signs that a neurologist should be involved include a rapid decline, signs of potential seizures, or that the patient doesn’t seem safe in their condition.

Neuropsychological testing is helpful, but it takes nearly 3 hours and may not be a good choice for restless or aggressive patients, Dr. Richie said.

Such testing is often not available, and if it is, insurance coverage is often a barrier because many plans don’t cover it.

Patients often ask about drugs and supplements they see advertised to help with memory loss. Medications are not helpful for mild cognitive impairment, although there is evidence that some are beneficial for patients with dementia, Dr. Richie said.

Celine Goetz, MD, assistant professor of internal medicine at Rush University Medical Center, Chicago, Illinois, told this news organization that it’s easy to relate to the fear that patients and families feel when cognitive impairment begins to emerge.

“[Dr.] Richie’s talk was right on point for internists like myself who see many patients with memory complaints, cognitive impairment, and dementia. I think we’re all terrified of losing our memory and the social and functional impairment that comes with that,” she said.

Although cognitive impairment and dementia aren’t curable or reversible, Dr. Goetz noted, internists can help patients optimize management of conditions such as diabetes and heart disease, which can affect cognitive function.

Dr. Richie pointed out that some interventions lack evidence for the treatment of mild cognitive impairment, but Dr. Goetz emphasized that resources are plentiful and can be effective in combination.

“Engaging social workers, pharmacists, nutritionists, physical and occupational therapists, and, on the inpatient side, delirium protocols, chaplains, and music therapists make a huge difference in patient care,” she said.

Dr. Richie and Dr. Goetz report no relevant financial relationships.

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

Although the COVID-19 pandemic put telehealth on fast forward, more than one third of patients in the United States engaged with telehealth services before February 2020, according to Ameet Doshi, MD, and Chrisanne Timpe, MD, of HealthPartners in Bloomington, Minn.

Broadly speaking, telehealth is “using virtual tools to evaluate, manage, and care for our patients, regardless of where they are located,” Dr. Doshi said during a May 6 session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The entirety of telehealth includes remote ways to meet almost any patient demand, he said. Some common health terms are used interchangeably, but some use telehealth as a broad term for electronic health care services, while telemedicine may refer specifically to remote patient care, he said.

Telemedicine allows flexibility of delivering patient care in inpatient, outpatient, or at-home settings, said Dr. Doshi. To illustrate the current application of telemedicine, he used an example of a 25-bed critical access hospital serving a growing regional population in which outpatient volume is expanding and ambulatory care services are being added. In this example, inpatient volume is growing, but not enough to support an inpatient consult service, but telehealth access to specialists such as cardiology would be useful in this case, he said.

Hospitalist telehealth means “being able to provide services to changing patient populations regardless of location; we can bring services to where patients are,” said Dr. Doshi.

Benefits of telehealth to patients include less travel and easier access to care, benefits to clinicians include expanding services at lower financial costs, he said.
 

COVID-19 challenges and opportunities

The COVID-19 pandemic presented both challenges and opportunities for telehealth, Dr. Doshi said. One opportunity was the sudden broad acceptance of virtual care out of necessity and concern for patient and staff safety, and to preserve the use of personal protective equipment, he said. In addition, a loosening of regulatory and financial pressures allowed more institutions to expand and initiate telehealth services.

Challenges included technological limitations and, in some cases, the need to develop a telehealth infrastructure from scratch, Dr. Doshi explained. Concerns also remain regarding how telehealth will evolve in the post-pandemic future, he said.

In the meantime, Medicare data show the impact of the pandemic on telehealth services, said Dr. Doshi. A telehealth waiver issued in March 2020 led to an increase in virtual encounters, and Medicare data show approximately 25 million virtual Medicare encounters between March 2020 and October 2020, representing a 3,000% increase from the same period in 2019, he said.

“Telehealth is here to stay, so the questions are how to craft a hospitalist telehealth program and provide essential patient care,” he said.

Dr. Timpe shared some examples of the evolution of telehealth care during the pandemic, including a case of an asymptomatic but frail patient with diabetes, dementia, and coronary artery disease undergoing outpatient care for a foot infection. The patient presented to an emergency department but refused to be hospitalized because of family concerns about patient isolation (no visitors were allowed at the time) and the concerns about COVID-19 infection.

The need to help treat acutely ill patients such as this patient while avoiding hospital admission during and after the pandemic continues to lead to the development of telehealth programs, Dr. Timpe said. She shared details of the Hospital@Home program developed by her organization, Health Partners. The program is designed to treat acutely ill people in the home, if possible, and avoid the need for hospital admission. Patients receive daily medical management from a hospitalist and care from staff, including registered nurses and community paramedics. Services include provision of IV medications and fluids, but the staff also conduct labs and imaging services, Dr. Timpe said.

Conditions that the program has managed at patients’ homes include pneumonia, COPD, asthma, bronchitis, flu, COVID-19, congestive heart failure, cellulitis, and urinary tract infections, said Dr. Timpe.

“We do not accept people into the program who have treatment needs that can only be met in a hospital,” such as the need for blood products, vasopressor support, telemetry, or positive pressure support, she noted.

Between November 2019 and February 15, 2021, the Hospital@Home program has provided services to 132 patients for a total of 287 visits. The program has averted 50 emergency department visits and 40 hospitalizations, and shorted hospital stays in 57 cases, she noted.

Hospitalists are suited for telehealth for several reasons, including the ability to triage acutely ill patients, familiarity with resource utilization, and expertise in management of complex medical care, said Dr. Timpe.
 

Looking ahead

Dr. Doshi emphasized several ongoing issues regarding the future of telemedicine, primarily the need for standardized regulation and reimbursement; reduction of health equity disparity and attention to technological barriers (including access and technology literacy); and identification of the next frontiers in telehealth.

Research on the impact and effectiveness of telehealth is limited, but growing, and next frontiers might include making patients more active participants in telehealth via patient-operated kits, or the option of an open telemedicine marketplace, in which patients can select providers from across the country, he said. No matter where telehealth leads in the future, “we need to make sure we have a positive patient outcome,” he concluded.

Dr. Doshi and Dr. Timpe had no financial conflicts to disclose.

Although the COVID-19 pandemic put telehealth on fast forward, more than one third of patients in the United States engaged with telehealth services before February 2020, according to Ameet Doshi, MD, and Chrisanne Timpe, MD, of HealthPartners in Bloomington, Minn.

Broadly speaking, telehealth is “using virtual tools to evaluate, manage, and care for our patients, regardless of where they are located,” Dr. Doshi said during a May 6 session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The entirety of telehealth includes remote ways to meet almost any patient demand, he said. Some common health terms are used interchangeably, but some use telehealth as a broad term for electronic health care services, while telemedicine may refer specifically to remote patient care, he said.

Telemedicine allows flexibility of delivering patient care in inpatient, outpatient, or at-home settings, said Dr. Doshi. To illustrate the current application of telemedicine, he used an example of a 25-bed critical access hospital serving a growing regional population in which outpatient volume is expanding and ambulatory care services are being added. In this example, inpatient volume is growing, but not enough to support an inpatient consult service, but telehealth access to specialists such as cardiology would be useful in this case, he said.

Hospitalist telehealth means “being able to provide services to changing patient populations regardless of location; we can bring services to where patients are,” said Dr. Doshi.

Benefits of telehealth to patients include less travel and easier access to care, benefits to clinicians include expanding services at lower financial costs, he said.
 

COVID-19 challenges and opportunities

The COVID-19 pandemic presented both challenges and opportunities for telehealth, Dr. Doshi said. One opportunity was the sudden broad acceptance of virtual care out of necessity and concern for patient and staff safety, and to preserve the use of personal protective equipment, he said. In addition, a loosening of regulatory and financial pressures allowed more institutions to expand and initiate telehealth services.

Challenges included technological limitations and, in some cases, the need to develop a telehealth infrastructure from scratch, Dr. Doshi explained. Concerns also remain regarding how telehealth will evolve in the post-pandemic future, he said.

In the meantime, Medicare data show the impact of the pandemic on telehealth services, said Dr. Doshi. A telehealth waiver issued in March 2020 led to an increase in virtual encounters, and Medicare data show approximately 25 million virtual Medicare encounters between March 2020 and October 2020, representing a 3,000% increase from the same period in 2019, he said.

“Telehealth is here to stay, so the questions are how to craft a hospitalist telehealth program and provide essential patient care,” he said.

Dr. Timpe shared some examples of the evolution of telehealth care during the pandemic, including a case of an asymptomatic but frail patient with diabetes, dementia, and coronary artery disease undergoing outpatient care for a foot infection. The patient presented to an emergency department but refused to be hospitalized because of family concerns about patient isolation (no visitors were allowed at the time) and the concerns about COVID-19 infection.

The need to help treat acutely ill patients such as this patient while avoiding hospital admission during and after the pandemic continues to lead to the development of telehealth programs, Dr. Timpe said. She shared details of the Hospital@Home program developed by her organization, Health Partners. The program is designed to treat acutely ill people in the home, if possible, and avoid the need for hospital admission. Patients receive daily medical management from a hospitalist and care from staff, including registered nurses and community paramedics. Services include provision of IV medications and fluids, but the staff also conduct labs and imaging services, Dr. Timpe said.

Conditions that the program has managed at patients’ homes include pneumonia, COPD, asthma, bronchitis, flu, COVID-19, congestive heart failure, cellulitis, and urinary tract infections, said Dr. Timpe.

“We do not accept people into the program who have treatment needs that can only be met in a hospital,” such as the need for blood products, vasopressor support, telemetry, or positive pressure support, she noted.

Between November 2019 and February 15, 2021, the Hospital@Home program has provided services to 132 patients for a total of 287 visits. The program has averted 50 emergency department visits and 40 hospitalizations, and shorted hospital stays in 57 cases, she noted.

Hospitalists are suited for telehealth for several reasons, including the ability to triage acutely ill patients, familiarity with resource utilization, and expertise in management of complex medical care, said Dr. Timpe.
 

Looking ahead

Dr. Doshi emphasized several ongoing issues regarding the future of telemedicine, primarily the need for standardized regulation and reimbursement; reduction of health equity disparity and attention to technological barriers (including access and technology literacy); and identification of the next frontiers in telehealth.

Research on the impact and effectiveness of telehealth is limited, but growing, and next frontiers might include making patients more active participants in telehealth via patient-operated kits, or the option of an open telemedicine marketplace, in which patients can select providers from across the country, he said. No matter where telehealth leads in the future, “we need to make sure we have a positive patient outcome,” he concluded.

Dr. Doshi and Dr. Timpe had no financial conflicts to disclose.

Although the COVID-19 pandemic put telehealth on fast forward, more than one third of patients in the United States engaged with telehealth services before February 2020, according to Ameet Doshi, MD, and Chrisanne Timpe, MD, of HealthPartners in Bloomington, Minn.

Broadly speaking, telehealth is “using virtual tools to evaluate, manage, and care for our patients, regardless of where they are located,” Dr. Doshi said during a May 6 session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The entirety of telehealth includes remote ways to meet almost any patient demand, he said. Some common health terms are used interchangeably, but some use telehealth as a broad term for electronic health care services, while telemedicine may refer specifically to remote patient care, he said.

Telemedicine allows flexibility of delivering patient care in inpatient, outpatient, or at-home settings, said Dr. Doshi. To illustrate the current application of telemedicine, he used an example of a 25-bed critical access hospital serving a growing regional population in which outpatient volume is expanding and ambulatory care services are being added. In this example, inpatient volume is growing, but not enough to support an inpatient consult service, but telehealth access to specialists such as cardiology would be useful in this case, he said.

Hospitalist telehealth means “being able to provide services to changing patient populations regardless of location; we can bring services to where patients are,” said Dr. Doshi.

Benefits of telehealth to patients include less travel and easier access to care, benefits to clinicians include expanding services at lower financial costs, he said.
 

COVID-19 challenges and opportunities

The COVID-19 pandemic presented both challenges and opportunities for telehealth, Dr. Doshi said. One opportunity was the sudden broad acceptance of virtual care out of necessity and concern for patient and staff safety, and to preserve the use of personal protective equipment, he said. In addition, a loosening of regulatory and financial pressures allowed more institutions to expand and initiate telehealth services.

Challenges included technological limitations and, in some cases, the need to develop a telehealth infrastructure from scratch, Dr. Doshi explained. Concerns also remain regarding how telehealth will evolve in the post-pandemic future, he said.

In the meantime, Medicare data show the impact of the pandemic on telehealth services, said Dr. Doshi. A telehealth waiver issued in March 2020 led to an increase in virtual encounters, and Medicare data show approximately 25 million virtual Medicare encounters between March 2020 and October 2020, representing a 3,000% increase from the same period in 2019, he said.

“Telehealth is here to stay, so the questions are how to craft a hospitalist telehealth program and provide essential patient care,” he said.

Dr. Timpe shared some examples of the evolution of telehealth care during the pandemic, including a case of an asymptomatic but frail patient with diabetes, dementia, and coronary artery disease undergoing outpatient care for a foot infection. The patient presented to an emergency department but refused to be hospitalized because of family concerns about patient isolation (no visitors were allowed at the time) and the concerns about COVID-19 infection.

The need to help treat acutely ill patients such as this patient while avoiding hospital admission during and after the pandemic continues to lead to the development of telehealth programs, Dr. Timpe said. She shared details of the Hospital@Home program developed by her organization, Health Partners. The program is designed to treat acutely ill people in the home, if possible, and avoid the need for hospital admission. Patients receive daily medical management from a hospitalist and care from staff, including registered nurses and community paramedics. Services include provision of IV medications and fluids, but the staff also conduct labs and imaging services, Dr. Timpe said.

Conditions that the program has managed at patients’ homes include pneumonia, COPD, asthma, bronchitis, flu, COVID-19, congestive heart failure, cellulitis, and urinary tract infections, said Dr. Timpe.

“We do not accept people into the program who have treatment needs that can only be met in a hospital,” such as the need for blood products, vasopressor support, telemetry, or positive pressure support, she noted.

Between November 2019 and February 15, 2021, the Hospital@Home program has provided services to 132 patients for a total of 287 visits. The program has averted 50 emergency department visits and 40 hospitalizations, and shorted hospital stays in 57 cases, she noted.

Hospitalists are suited for telehealth for several reasons, including the ability to triage acutely ill patients, familiarity with resource utilization, and expertise in management of complex medical care, said Dr. Timpe.
 

Looking ahead

Dr. Doshi emphasized several ongoing issues regarding the future of telemedicine, primarily the need for standardized regulation and reimbursement; reduction of health equity disparity and attention to technological barriers (including access and technology literacy); and identification of the next frontiers in telehealth.

Research on the impact and effectiveness of telehealth is limited, but growing, and next frontiers might include making patients more active participants in telehealth via patient-operated kits, or the option of an open telemedicine marketplace, in which patients can select providers from across the country, he said. No matter where telehealth leads in the future, “we need to make sure we have a positive patient outcome,” he concluded.

Dr. Doshi and Dr. Timpe had no financial conflicts to disclose.

If you don’t have a standardized process for obstructive sleep apnea screening of all patients heading into the operating room at your hospital you should, because perioperative pulmonary complications can occur, according to Efren C. Manjarrez MD, SFHM, FACP.

If OSA is not documented in the patient’s chart, you may find yourself making a bedside assessment. “I usually don’t ask the patients this because they can’t necessarily answer the questions,” Dr. Manjarrez, associate professor in the division of hospital medicine at the University of Miami, said at SHM Converge, the annual conference of the Society of Hospital Medicine. “So, I ask their partner: ‘Does your partner snore loudly? Are they sleepy during the daytime, or are they gasping or choking in the middle of the night?’”

The following factors have a relatively high specificity for OSA: a STOP-Bang score of 5 or greater, a STOP-Bang score of 2 or greater plus male gender, and a STOP-Bang score of 2 or greater plus a body mass index greater than 35 kg/m². Clinicians can also check the Mallampati score on their patients by having them tilt their heads back and stick out their tongues.

“If the uvula is not touching the tongue, that’s a Mallampati score of 1; that’s a pretty wide-open airway,” Dr. Manjarrez said. “However, when you do not have any form of an airway and the palate is touching the tongue, that is a Mallampati score of 4, which indicates OSA.”

Other objective data suggestive of OSA include high blood pressure, a BMI over 35 kg/m², a neck circumference of greater than 40 cm, and male gender. In a study of patients who presented for surgery who did not have a diagnosis of sleep apnea, a high STOP-Bang score indicated a high probability of moderate to severe sleep apnea (Br J. Anaesth 2012;108[5]:768-75).

“If the STOP-Bang score is 0-2, your workup stops,” Dr. Manjarrez said. “If your STOP-Bang score is 5 or above, there’s a high likelihood they have moderate or severe sleep apnea. Patients who have a STOP-Bang of 3-4, calculate their STOP score. If the STOP score is 2 or more and they’re male, obese, and have a neck circumference of greater than 40 cm, there’s a pretty good chance they’ve got OSA.”

Screening for OSA prior to surgery matters, because the potential pulmonary complications are fairly high, “anywhere from postoperative respiratory failure to COPD exacerbation and hypoxia to pneumonia,” he continued. “These patients very commonly desaturate and are difficult for the anesthesiologists to intubate. Fortunately, we have not found significant cardiac complications in the medical literature, but we do know that patients with OSA commonly get postoperative atrial fibrillation. There are also combined complications like desaturation and AFib and difficult intubations. Patients with sleep apnea do have a higher resource utilization perioperatively. Fortunately, at this point in time the data does not show that patients with OSA going in for surgery have an increased mortality.”

To optimize the care of these patients prior to surgery, Dr. Manjarrez recommends that hospitalists document that a patient either has known OSA or suspected OSA. “If possible, obtain their sleep study results and recommended PAP settings,” he said. “Ask patients to bring their PAP device to the hospital or to assure the hospital has appropriate surrogate devices available. You also want to advise the patient and the perioperative care team of the increased risk of complications in patients at high risk for OSA and optimize other conditions that may impair cardiorespiratory function.”

Perioperative risk reduction strategies include planning for difficult intubation and mask ventilation, using regional anesthesia and analgesia, using sedatives with caution, minimizing the use of opioids and anticipating variable opioid responses. “When I have a patient with suspected sleep apnea and no red flags I write down ‘OSA precautions,’ in the chart, which means elevate the head of the bed, perform continuous pulse oximetry, and cautiously supply supplemental oxygen as needed,” he said.

Postoperatively, he continued, minimize sedative agents and opioids, use regional and nonopioid analgesics when possible, provide supplemental oxygen until the patient is able to maintain baseline SaO₂ on room air in a monitored setting, maintain the patient in nonsupine position when feasible, and continuously monitor pulse oximetry.

Consider delay of elective surgery and referral to a sleep medicine specialist in cases of uncontrolled systemic conditions or impaired gas exchange, including hypoventilation syndromes (a clue being a serum HC03 of 28 or higher), severe pulmonary hypertension (a clue being right ventricular systolic blood pressure or pulmonary systolic pressure of 70 mm Hg or above, or right ventricular dilatation/dysfunction), and hypoxemia not explained by cardiac disease.

A systematic review and meta-analysis of six studies that included 904 patients with sleep apnea found that there was no significant difference in the postoperative adverse events between CPAP and no-CPAP treatment (Anesth Analg 2015;120:1013-23). However, there was a significant reduction in the Apnea-Hypopnea Index postoperatively among those who used CPAP (37 vs. 12 events per hour; P less than .001), as well as a significant reduction in hospital length of stay 4 vs. 4.4 days; P = .05).

Dr. Manjarrez reported having no financial disclosures.

If you don’t have a standardized process for obstructive sleep apnea screening of all patients heading into the operating room at your hospital you should, because perioperative pulmonary complications can occur, according to Efren C. Manjarrez MD, SFHM, FACP.

If OSA is not documented in the patient’s chart, you may find yourself making a bedside assessment. “I usually don’t ask the patients this because they can’t necessarily answer the questions,” Dr. Manjarrez, associate professor in the division of hospital medicine at the University of Miami, said at SHM Converge, the annual conference of the Society of Hospital Medicine. “So, I ask their partner: ‘Does your partner snore loudly? Are they sleepy during the daytime, or are they gasping or choking in the middle of the night?’”

The following factors have a relatively high specificity for OSA: a STOP-Bang score of 5 or greater, a STOP-Bang score of 2 or greater plus male gender, and a STOP-Bang score of 2 or greater plus a body mass index greater than 35 kg/m². Clinicians can also check the Mallampati score on their patients by having them tilt their heads back and stick out their tongues.

“If the uvula is not touching the tongue, that’s a Mallampati score of 1; that’s a pretty wide-open airway,” Dr. Manjarrez said. “However, when you do not have any form of an airway and the palate is touching the tongue, that is a Mallampati score of 4, which indicates OSA.”

Other objective data suggestive of OSA include high blood pressure, a BMI over 35 kg/m², a neck circumference of greater than 40 cm, and male gender. In a study of patients who presented for surgery who did not have a diagnosis of sleep apnea, a high STOP-Bang score indicated a high probability of moderate to severe sleep apnea (Br J. Anaesth 2012;108[5]:768-75).

“If the STOP-Bang score is 0-2, your workup stops,” Dr. Manjarrez said. “If your STOP-Bang score is 5 or above, there’s a high likelihood they have moderate or severe sleep apnea. Patients who have a STOP-Bang of 3-4, calculate their STOP score. If the STOP score is 2 or more and they’re male, obese, and have a neck circumference of greater than 40 cm, there’s a pretty good chance they’ve got OSA.”

Screening for OSA prior to surgery matters, because the potential pulmonary complications are fairly high, “anywhere from postoperative respiratory failure to COPD exacerbation and hypoxia to pneumonia,” he continued. “These patients very commonly desaturate and are difficult for the anesthesiologists to intubate. Fortunately, we have not found significant cardiac complications in the medical literature, but we do know that patients with OSA commonly get postoperative atrial fibrillation. There are also combined complications like desaturation and AFib and difficult intubations. Patients with sleep apnea do have a higher resource utilization perioperatively. Fortunately, at this point in time the data does not show that patients with OSA going in for surgery have an increased mortality.”

To optimize the care of these patients prior to surgery, Dr. Manjarrez recommends that hospitalists document that a patient either has known OSA or suspected OSA. “If possible, obtain their sleep study results and recommended PAP settings,” he said. “Ask patients to bring their PAP device to the hospital or to assure the hospital has appropriate surrogate devices available. You also want to advise the patient and the perioperative care team of the increased risk of complications in patients at high risk for OSA and optimize other conditions that may impair cardiorespiratory function.”

Perioperative risk reduction strategies include planning for difficult intubation and mask ventilation, using regional anesthesia and analgesia, using sedatives with caution, minimizing the use of opioids and anticipating variable opioid responses. “When I have a patient with suspected sleep apnea and no red flags I write down ‘OSA precautions,’ in the chart, which means elevate the head of the bed, perform continuous pulse oximetry, and cautiously supply supplemental oxygen as needed,” he said.

Postoperatively, he continued, minimize sedative agents and opioids, use regional and nonopioid analgesics when possible, provide supplemental oxygen until the patient is able to maintain baseline SaO₂ on room air in a monitored setting, maintain the patient in nonsupine position when feasible, and continuously monitor pulse oximetry.

Consider delay of elective surgery and referral to a sleep medicine specialist in cases of uncontrolled systemic conditions or impaired gas exchange, including hypoventilation syndromes (a clue being a serum HC03 of 28 or higher), severe pulmonary hypertension (a clue being right ventricular systolic blood pressure or pulmonary systolic pressure of 70 mm Hg or above, or right ventricular dilatation/dysfunction), and hypoxemia not explained by cardiac disease.

A systematic review and meta-analysis of six studies that included 904 patients with sleep apnea found that there was no significant difference in the postoperative adverse events between CPAP and no-CPAP treatment (Anesth Analg 2015;120:1013-23). However, there was a significant reduction in the Apnea-Hypopnea Index postoperatively among those who used CPAP (37 vs. 12 events per hour; P less than .001), as well as a significant reduction in hospital length of stay 4 vs. 4.4 days; P = .05).

Dr. Manjarrez reported having no financial disclosures.

If you don’t have a standardized process for obstructive sleep apnea screening of all patients heading into the operating room at your hospital you should, because perioperative pulmonary complications can occur, according to Efren C. Manjarrez MD, SFHM, FACP.

If OSA is not documented in the patient’s chart, you may find yourself making a bedside assessment. “I usually don’t ask the patients this because they can’t necessarily answer the questions,” Dr. Manjarrez, associate professor in the division of hospital medicine at the University of Miami, said at SHM Converge, the annual conference of the Society of Hospital Medicine. “So, I ask their partner: ‘Does your partner snore loudly? Are they sleepy during the daytime, or are they gasping or choking in the middle of the night?’”

The following factors have a relatively high specificity for OSA: a STOP-Bang score of 5 or greater, a STOP-Bang score of 2 or greater plus male gender, and a STOP-Bang score of 2 or greater plus a body mass index greater than 35 kg/m². Clinicians can also check the Mallampati score on their patients by having them tilt their heads back and stick out their tongues.

“If the uvula is not touching the tongue, that’s a Mallampati score of 1; that’s a pretty wide-open airway,” Dr. Manjarrez said. “However, when you do not have any form of an airway and the palate is touching the tongue, that is a Mallampati score of 4, which indicates OSA.”

Other objective data suggestive of OSA include high blood pressure, a BMI over 35 kg/m², a neck circumference of greater than 40 cm, and male gender. In a study of patients who presented for surgery who did not have a diagnosis of sleep apnea, a high STOP-Bang score indicated a high probability of moderate to severe sleep apnea (Br J. Anaesth 2012;108[5]:768-75).

“If the STOP-Bang score is 0-2, your workup stops,” Dr. Manjarrez said. “If your STOP-Bang score is 5 or above, there’s a high likelihood they have moderate or severe sleep apnea. Patients who have a STOP-Bang of 3-4, calculate their STOP score. If the STOP score is 2 or more and they’re male, obese, and have a neck circumference of greater than 40 cm, there’s a pretty good chance they’ve got OSA.”

Screening for OSA prior to surgery matters, because the potential pulmonary complications are fairly high, “anywhere from postoperative respiratory failure to COPD exacerbation and hypoxia to pneumonia,” he continued. “These patients very commonly desaturate and are difficult for the anesthesiologists to intubate. Fortunately, we have not found significant cardiac complications in the medical literature, but we do know that patients with OSA commonly get postoperative atrial fibrillation. There are also combined complications like desaturation and AFib and difficult intubations. Patients with sleep apnea do have a higher resource utilization perioperatively. Fortunately, at this point in time the data does not show that patients with OSA going in for surgery have an increased mortality.”

To optimize the care of these patients prior to surgery, Dr. Manjarrez recommends that hospitalists document that a patient either has known OSA or suspected OSA. “If possible, obtain their sleep study results and recommended PAP settings,” he said. “Ask patients to bring their PAP device to the hospital or to assure the hospital has appropriate surrogate devices available. You also want to advise the patient and the perioperative care team of the increased risk of complications in patients at high risk for OSA and optimize other conditions that may impair cardiorespiratory function.”

Perioperative risk reduction strategies include planning for difficult intubation and mask ventilation, using regional anesthesia and analgesia, using sedatives with caution, minimizing the use of opioids and anticipating variable opioid responses. “When I have a patient with suspected sleep apnea and no red flags I write down ‘OSA precautions,’ in the chart, which means elevate the head of the bed, perform continuous pulse oximetry, and cautiously supply supplemental oxygen as needed,” he said.

Postoperatively, he continued, minimize sedative agents and opioids, use regional and nonopioid analgesics when possible, provide supplemental oxygen until the patient is able to maintain baseline SaO₂ on room air in a monitored setting, maintain the patient in nonsupine position when feasible, and continuously monitor pulse oximetry.

Consider delay of elective surgery and referral to a sleep medicine specialist in cases of uncontrolled systemic conditions or impaired gas exchange, including hypoventilation syndromes (a clue being a serum HC03 of 28 or higher), severe pulmonary hypertension (a clue being right ventricular systolic blood pressure or pulmonary systolic pressure of 70 mm Hg or above, or right ventricular dilatation/dysfunction), and hypoxemia not explained by cardiac disease.

A systematic review and meta-analysis of six studies that included 904 patients with sleep apnea found that there was no significant difference in the postoperative adverse events between CPAP and no-CPAP treatment (Anesth Analg 2015;120:1013-23). However, there was a significant reduction in the Apnea-Hypopnea Index postoperatively among those who used CPAP (37 vs. 12 events per hour; P less than .001), as well as a significant reduction in hospital length of stay 4 vs. 4.4 days; P = .05).

Dr. Manjarrez reported having no financial disclosures.

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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