This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

Key clinical point: Baricitinib vs. dupilumab demonstrated similar efficacy in reducing atopic dermatitis (AD) severity and improving quality of life (QoL), with more rapid improvement in itch.

Major finding: A dose of 4 mg baricitinib vs. dupilumab as monotherapy or with topical corticosteroids (TCS) was more likely to show ≥4-point improvement in itch scores at 4 weeks among patients with inadequate response or intolerance to topical treatments (dupliumab: relative risk [RR] 2.62; P = .013; TCS: RR 2.16; P = .029). However, both drugs showed similar efficacy across Eczema Area and Severity Index 75, itch, and QoL scores at 16 weeks.

Study details: This data comes from an indirect treatment comparison analysis of nine placebo-controlled trials included 3364 adults with moderate-to-severe AD and inadequate response or intolerance to topical treatments or cyclosporine who received dupilumab ± TCS or baricitinib ± TCS.

Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees or shareholders of Eli Lilly. The other authors reported ties with various sources, including Eli Lilly.

Source: de Bruin-Weller MS et al. Indirect treatment comparison of baricitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2022 (May 11). Doi: 10.1007/s13555-022-00734-w

Key clinical point: Baricitinib vs. dupilumab demonstrated similar efficacy in reducing atopic dermatitis (AD) severity and improving quality of life (QoL), with more rapid improvement in itch.

Major finding: A dose of 4 mg baricitinib vs. dupilumab as monotherapy or with topical corticosteroids (TCS) was more likely to show ≥4-point improvement in itch scores at 4 weeks among patients with inadequate response or intolerance to topical treatments (dupliumab: relative risk [RR] 2.62; P = .013; TCS: RR 2.16; P = .029). However, both drugs showed similar efficacy across Eczema Area and Severity Index 75, itch, and QoL scores at 16 weeks.

Study details: This data comes from an indirect treatment comparison analysis of nine placebo-controlled trials included 3364 adults with moderate-to-severe AD and inadequate response or intolerance to topical treatments or cyclosporine who received dupilumab ± TCS or baricitinib ± TCS.

Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees or shareholders of Eli Lilly. The other authors reported ties with various sources, including Eli Lilly.

Source: de Bruin-Weller MS et al. Indirect treatment comparison of baricitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2022 (May 11). Doi: 10.1007/s13555-022-00734-w

Key clinical point: Baricitinib vs. dupilumab demonstrated similar efficacy in reducing atopic dermatitis (AD) severity and improving quality of life (QoL), with more rapid improvement in itch.

Major finding: A dose of 4 mg baricitinib vs. dupilumab as monotherapy or with topical corticosteroids (TCS) was more likely to show ≥4-point improvement in itch scores at 4 weeks among patients with inadequate response or intolerance to topical treatments (dupliumab: relative risk [RR] 2.62; P = .013; TCS: RR 2.16; P = .029). However, both drugs showed similar efficacy across Eczema Area and Severity Index 75, itch, and QoL scores at 16 weeks.

Study details: This data comes from an indirect treatment comparison analysis of nine placebo-controlled trials included 3364 adults with moderate-to-severe AD and inadequate response or intolerance to topical treatments or cyclosporine who received dupilumab ± TCS or baricitinib ± TCS.

Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees or shareholders of Eli Lilly. The other authors reported ties with various sources, including Eli Lilly.

Source: de Bruin-Weller MS et al. Indirect treatment comparison of baricitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2022 (May 11). Doi: 10.1007/s13555-022-00734-w

A 35-year-old female with a complex psychiatric history and polysubstance use presents to the emergency department following ingestion of three sewing needles. The patient has a long history of multiple suicide attempts and foreign-body ingestions requiring repeated endoscopy. Prior ingestions include, but are not limited to, razor blades, screws, toothbrushes, batteries, plastic cutlery, and shower curtain rings. The patient has had over 50 upper endoscopies within the past year in addition to a laryngoscopy and bronchoscopy for retrieval of foreign bodies. Despite intensive inpatient psychiatric treatment and outpatient behavioral therapy, the patient continues to present with recurrent ingestions, creating frustration among multiple health care providers. Are gastroenterologists obligated to perform repeated endoscopies for recurrent foreign-body ingestions? Is there a point at which it would be medically and ethically appropriate to defer endoscopy in this clinical scenario?

Deliberate foreign-body ingestion (DFBI) is a psychological disorder in which patients swallow nonnutritive objects. The disorder is commonly seen in young female patients with psychiatric disorders.¹ It is also associated with substance abuse, intellectual disabilities, and malingering (such as external motivation to avoid jail). Of those with psychiatric disorders, repeat ingestions are primarily seen in patients with borderline personality disorder (BPD) or part of a syndrome of self-mutilation or attention-seeking behavior.² Patients with BPD are thought to have atrophic changes in the brain causing neurocognitive dysfunction accounting for such behaviors.¹ Self-injurious behavior is also associated with a history of abandonment and childhood abuse.³ Studies show that 85% of patients evaluated for DFBI have a prior psychiatric diagnosis and 84% of these patients have a history of prior ingestions.⁴

One of the fundamental principles of medical ethics is beneficence, supporting the notion that all providers should act in the best interest of the patient. Adults may make poor or self-destructive choices, but that does not preclude our moral obligation to treat them. Patients with substance abuse disorders may repeatedly use emergency room services for acute intoxication and overdose treatment. An emergency department physician would not withhold Narcan from a patient simply because of the frequency of repeated overdoses. A similar rationale could be applied to patients with DFBI – they should undergo endoscopy if they are accepting of the risks/benefits of repeated procedures. Given that this patient’s repeated ingestions are suicide attempts, it could be argued that not removing the object would make a clinician complicit with a patient’s suicide attempt or intent of self-harm.

From an alternative vantage point, patients with repeated DFBI have an increased risk of complications with repeated endoscopy, especially when performed emergently. Patients may have an increased risk of aspiration because of insufficient preoperative fasting, and attempted removal of ingested needles and other sharp objects carries a high risk of penetrating trauma, bleeding, and perforation. The patient’s swallowing history predicts a high likelihood of repeat ingestion which, over time, makes subsequent endoscopies seem futile. Endoscopic treatment does not address the underlying problem and only serves as a temporary fix to bridge the patient to their next ingestion. Furthermore, the utilization of resources is substantial – namely, the repeated emergency use of anesthesia and operating room and endoscopy staff, as well as the psychiatry, surgical, internal medicine, and gastroenterology services. Inevitably, treatment of a patient such as this diverts limited health care resources away from other patients who may have equally or more pressing medical needs.

Despite the seemingly futile nature of these procedures and strain on resources, it would be difficult from a medicolegal perspective to justify withholding endoscopy. In 1986, the Emergency Medical Treatment and Labor Act was enacted that requires anyone presenting to an emergency department to be stabilized and treated.⁷ In this particular patient case, an ethics consultation was obtained and recommended that the patient continue to undergo endoscopy. However, the team also suggested that a multidisciplinary meeting with ethics, the primary and procedural teams, and the hospital’s medicolegal department be held to further elucidate a plan for future admissions and to decide if or when it may be appropriate to withhold invasive procedures. This case was presented at our weekly gastroenterology grand rounds, and procedural guidelines were reviewed. Given the size and nature of most of the objects the patient ingests, we reviewed that it would be safe in the majority of scenarios to wait until the morning for removal if called overnight – providing some relief to those on call while minimizing utilization of emergency anesthesia resources as well as operating room and endoscopy staff.

Caring for these patients is challenging as providers may feel frustrated and angry after repeated admissions. The patient may sense the low morale from providers and feel judged for their actions. It is theorized that this leads to repeated ingestions as a defense mechanism and a means of acting out.¹ Additionally, friction can develop between teams as there is a common perception that psychiatry is not “doing enough” to treat the psychiatric disorder to prevent recurrences.⁸

In conclusion, DFBIs occur in a small number of patients with psychiatric disorders, but account for a large utilization of health care recourses. Gastroenterologists have an ethical and legal obligation to provide treatment including repeat endoscopies as long as the therapeutic benefit of the procedure outweighs risks. A multidisciplinary approach with individualized care plans can help prevent recurrent hospitalizations and procedures which may, in turn, improve outcomes and reduce health care costs.¹ Until the patient and clinicians can successfully mitigate the psychiatric and social factors perpetuating repeated ingestions, gastroenterologists will continue to provide endoscopic management. Individual cases should be discussed with the hospital’s ethics and medicolegal teams for further guidance on deferring endoscopic treatment in cases of medically refractory psychological disease.

Dr. Sims is a gastroenterology fellow in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. Dr. Rao is assistant professor in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. They had no conflicts of interest to disclose.

References

1. Bangash F et al. Cureus. 2021 Feb;13(2):e13179. doi: 10.7759/cureus.13179

2. Palese C et al. Gastroenterol Hepatol (N Y). 2012 July;8(7):485-6

3. Gitlin GF et al. Psychosomatics, 2007 March;48(2):162-6. doi: 10.1176/appi.psy.48.2.162

4. Palta R et al. Gastrointest Endosc. 2009 March;69(3):426-33. doi: 10.1016/j.gie.2008.05.072

5. Huang BL et al. Clin Gastroenterol Hepatol. 2010 Nov;8(11):941-6. doi: 10.1016/j.cgh.2010.07.013

6. Poynter BA et al. Gen Hosp Psychiatry. 2011 Sep-Oct;33(5):518-24. doi: 10.1016/j.genhosppsych.2011.06.011

7. American College of Emergency Physicians, EMTALA Fact Sheet. https://www.acep.org/life-as-a-physician/ethics--legal/emtala/emtala-fact-sheet/

8. Grzenda A. Carlat Hosp Psych Report. 2021 Jan;1(1 ):5-9

A 35-year-old female with a complex psychiatric history and polysubstance use presents to the emergency department following ingestion of three sewing needles. The patient has a long history of multiple suicide attempts and foreign-body ingestions requiring repeated endoscopy. Prior ingestions include, but are not limited to, razor blades, screws, toothbrushes, batteries, plastic cutlery, and shower curtain rings. The patient has had over 50 upper endoscopies within the past year in addition to a laryngoscopy and bronchoscopy for retrieval of foreign bodies. Despite intensive inpatient psychiatric treatment and outpatient behavioral therapy, the patient continues to present with recurrent ingestions, creating frustration among multiple health care providers. Are gastroenterologists obligated to perform repeated endoscopies for recurrent foreign-body ingestions? Is there a point at which it would be medically and ethically appropriate to defer endoscopy in this clinical scenario?

Deliberate foreign-body ingestion (DFBI) is a psychological disorder in which patients swallow nonnutritive objects. The disorder is commonly seen in young female patients with psychiatric disorders.¹ It is also associated with substance abuse, intellectual disabilities, and malingering (such as external motivation to avoid jail). Of those with psychiatric disorders, repeat ingestions are primarily seen in patients with borderline personality disorder (BPD) or part of a syndrome of self-mutilation or attention-seeking behavior.² Patients with BPD are thought to have atrophic changes in the brain causing neurocognitive dysfunction accounting for such behaviors.¹ Self-injurious behavior is also associated with a history of abandonment and childhood abuse.³ Studies show that 85% of patients evaluated for DFBI have a prior psychiatric diagnosis and 84% of these patients have a history of prior ingestions.⁴

One of the fundamental principles of medical ethics is beneficence, supporting the notion that all providers should act in the best interest of the patient. Adults may make poor or self-destructive choices, but that does not preclude our moral obligation to treat them. Patients with substance abuse disorders may repeatedly use emergency room services for acute intoxication and overdose treatment. An emergency department physician would not withhold Narcan from a patient simply because of the frequency of repeated overdoses. A similar rationale could be applied to patients with DFBI – they should undergo endoscopy if they are accepting of the risks/benefits of repeated procedures. Given that this patient’s repeated ingestions are suicide attempts, it could be argued that not removing the object would make a clinician complicit with a patient’s suicide attempt or intent of self-harm.

From an alternative vantage point, patients with repeated DFBI have an increased risk of complications with repeated endoscopy, especially when performed emergently. Patients may have an increased risk of aspiration because of insufficient preoperative fasting, and attempted removal of ingested needles and other sharp objects carries a high risk of penetrating trauma, bleeding, and perforation. The patient’s swallowing history predicts a high likelihood of repeat ingestion which, over time, makes subsequent endoscopies seem futile. Endoscopic treatment does not address the underlying problem and only serves as a temporary fix to bridge the patient to their next ingestion. Furthermore, the utilization of resources is substantial – namely, the repeated emergency use of anesthesia and operating room and endoscopy staff, as well as the psychiatry, surgical, internal medicine, and gastroenterology services. Inevitably, treatment of a patient such as this diverts limited health care resources away from other patients who may have equally or more pressing medical needs.

Despite the seemingly futile nature of these procedures and strain on resources, it would be difficult from a medicolegal perspective to justify withholding endoscopy. In 1986, the Emergency Medical Treatment and Labor Act was enacted that requires anyone presenting to an emergency department to be stabilized and treated.⁷ In this particular patient case, an ethics consultation was obtained and recommended that the patient continue to undergo endoscopy. However, the team also suggested that a multidisciplinary meeting with ethics, the primary and procedural teams, and the hospital’s medicolegal department be held to further elucidate a plan for future admissions and to decide if or when it may be appropriate to withhold invasive procedures. This case was presented at our weekly gastroenterology grand rounds, and procedural guidelines were reviewed. Given the size and nature of most of the objects the patient ingests, we reviewed that it would be safe in the majority of scenarios to wait until the morning for removal if called overnight – providing some relief to those on call while minimizing utilization of emergency anesthesia resources as well as operating room and endoscopy staff.

Caring for these patients is challenging as providers may feel frustrated and angry after repeated admissions. The patient may sense the low morale from providers and feel judged for their actions. It is theorized that this leads to repeated ingestions as a defense mechanism and a means of acting out.¹ Additionally, friction can develop between teams as there is a common perception that psychiatry is not “doing enough” to treat the psychiatric disorder to prevent recurrences.⁸

In conclusion, DFBIs occur in a small number of patients with psychiatric disorders, but account for a large utilization of health care recourses. Gastroenterologists have an ethical and legal obligation to provide treatment including repeat endoscopies as long as the therapeutic benefit of the procedure outweighs risks. A multidisciplinary approach with individualized care plans can help prevent recurrent hospitalizations and procedures which may, in turn, improve outcomes and reduce health care costs.¹ Until the patient and clinicians can successfully mitigate the psychiatric and social factors perpetuating repeated ingestions, gastroenterologists will continue to provide endoscopic management. Individual cases should be discussed with the hospital’s ethics and medicolegal teams for further guidance on deferring endoscopic treatment in cases of medically refractory psychological disease.

Dr. Sims is a gastroenterology fellow in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. Dr. Rao is assistant professor in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. They had no conflicts of interest to disclose.

References

1. Bangash F et al. Cureus. 2021 Feb;13(2):e13179. doi: 10.7759/cureus.13179

2. Palese C et al. Gastroenterol Hepatol (N Y). 2012 July;8(7):485-6

3. Gitlin GF et al. Psychosomatics, 2007 March;48(2):162-6. doi: 10.1176/appi.psy.48.2.162

4. Palta R et al. Gastrointest Endosc. 2009 March;69(3):426-33. doi: 10.1016/j.gie.2008.05.072

5. Huang BL et al. Clin Gastroenterol Hepatol. 2010 Nov;8(11):941-6. doi: 10.1016/j.cgh.2010.07.013

6. Poynter BA et al. Gen Hosp Psychiatry. 2011 Sep-Oct;33(5):518-24. doi: 10.1016/j.genhosppsych.2011.06.011

7. American College of Emergency Physicians, EMTALA Fact Sheet. https://www.acep.org/life-as-a-physician/ethics--legal/emtala/emtala-fact-sheet/

8. Grzenda A. Carlat Hosp Psych Report. 2021 Jan;1(1 ):5-9

A 35-year-old female with a complex psychiatric history and polysubstance use presents to the emergency department following ingestion of three sewing needles. The patient has a long history of multiple suicide attempts and foreign-body ingestions requiring repeated endoscopy. Prior ingestions include, but are not limited to, razor blades, screws, toothbrushes, batteries, plastic cutlery, and shower curtain rings. The patient has had over 50 upper endoscopies within the past year in addition to a laryngoscopy and bronchoscopy for retrieval of foreign bodies. Despite intensive inpatient psychiatric treatment and outpatient behavioral therapy, the patient continues to present with recurrent ingestions, creating frustration among multiple health care providers. Are gastroenterologists obligated to perform repeated endoscopies for recurrent foreign-body ingestions? Is there a point at which it would be medically and ethically appropriate to defer endoscopy in this clinical scenario?

Deliberate foreign-body ingestion (DFBI) is a psychological disorder in which patients swallow nonnutritive objects. The disorder is commonly seen in young female patients with psychiatric disorders.¹ It is also associated with substance abuse, intellectual disabilities, and malingering (such as external motivation to avoid jail). Of those with psychiatric disorders, repeat ingestions are primarily seen in patients with borderline personality disorder (BPD) or part of a syndrome of self-mutilation or attention-seeking behavior.² Patients with BPD are thought to have atrophic changes in the brain causing neurocognitive dysfunction accounting for such behaviors.¹ Self-injurious behavior is also associated with a history of abandonment and childhood abuse.³ Studies show that 85% of patients evaluated for DFBI have a prior psychiatric diagnosis and 84% of these patients have a history of prior ingestions.⁴

One of the fundamental principles of medical ethics is beneficence, supporting the notion that all providers should act in the best interest of the patient. Adults may make poor or self-destructive choices, but that does not preclude our moral obligation to treat them. Patients with substance abuse disorders may repeatedly use emergency room services for acute intoxication and overdose treatment. An emergency department physician would not withhold Narcan from a patient simply because of the frequency of repeated overdoses. A similar rationale could be applied to patients with DFBI – they should undergo endoscopy if they are accepting of the risks/benefits of repeated procedures. Given that this patient’s repeated ingestions are suicide attempts, it could be argued that not removing the object would make a clinician complicit with a patient’s suicide attempt or intent of self-harm.

From an alternative vantage point, patients with repeated DFBI have an increased risk of complications with repeated endoscopy, especially when performed emergently. Patients may have an increased risk of aspiration because of insufficient preoperative fasting, and attempted removal of ingested needles and other sharp objects carries a high risk of penetrating trauma, bleeding, and perforation. The patient’s swallowing history predicts a high likelihood of repeat ingestion which, over time, makes subsequent endoscopies seem futile. Endoscopic treatment does not address the underlying problem and only serves as a temporary fix to bridge the patient to their next ingestion. Furthermore, the utilization of resources is substantial – namely, the repeated emergency use of anesthesia and operating room and endoscopy staff, as well as the psychiatry, surgical, internal medicine, and gastroenterology services. Inevitably, treatment of a patient such as this diverts limited health care resources away from other patients who may have equally or more pressing medical needs.

Despite the seemingly futile nature of these procedures and strain on resources, it would be difficult from a medicolegal perspective to justify withholding endoscopy. In 1986, the Emergency Medical Treatment and Labor Act was enacted that requires anyone presenting to an emergency department to be stabilized and treated.⁷ In this particular patient case, an ethics consultation was obtained and recommended that the patient continue to undergo endoscopy. However, the team also suggested that a multidisciplinary meeting with ethics, the primary and procedural teams, and the hospital’s medicolegal department be held to further elucidate a plan for future admissions and to decide if or when it may be appropriate to withhold invasive procedures. This case was presented at our weekly gastroenterology grand rounds, and procedural guidelines were reviewed. Given the size and nature of most of the objects the patient ingests, we reviewed that it would be safe in the majority of scenarios to wait until the morning for removal if called overnight – providing some relief to those on call while minimizing utilization of emergency anesthesia resources as well as operating room and endoscopy staff.

Caring for these patients is challenging as providers may feel frustrated and angry after repeated admissions. The patient may sense the low morale from providers and feel judged for their actions. It is theorized that this leads to repeated ingestions as a defense mechanism and a means of acting out.¹ Additionally, friction can develop between teams as there is a common perception that psychiatry is not “doing enough” to treat the psychiatric disorder to prevent recurrences.⁸

In conclusion, DFBIs occur in a small number of patients with psychiatric disorders, but account for a large utilization of health care recourses. Gastroenterologists have an ethical and legal obligation to provide treatment including repeat endoscopies as long as the therapeutic benefit of the procedure outweighs risks. A multidisciplinary approach with individualized care plans can help prevent recurrent hospitalizations and procedures which may, in turn, improve outcomes and reduce health care costs.¹ Until the patient and clinicians can successfully mitigate the psychiatric and social factors perpetuating repeated ingestions, gastroenterologists will continue to provide endoscopic management. Individual cases should be discussed with the hospital’s ethics and medicolegal teams for further guidance on deferring endoscopic treatment in cases of medically refractory psychological disease.

Dr. Sims is a gastroenterology fellow in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. Dr. Rao is assistant professor in the section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago Medicine. They had no conflicts of interest to disclose.

References

1. Bangash F et al. Cureus. 2021 Feb;13(2):e13179. doi: 10.7759/cureus.13179

2. Palese C et al. Gastroenterol Hepatol (N Y). 2012 July;8(7):485-6

3. Gitlin GF et al. Psychosomatics, 2007 March;48(2):162-6. doi: 10.1176/appi.psy.48.2.162

4. Palta R et al. Gastrointest Endosc. 2009 March;69(3):426-33. doi: 10.1016/j.gie.2008.05.072

5. Huang BL et al. Clin Gastroenterol Hepatol. 2010 Nov;8(11):941-6. doi: 10.1016/j.cgh.2010.07.013

6. Poynter BA et al. Gen Hosp Psychiatry. 2011 Sep-Oct;33(5):518-24. doi: 10.1016/j.genhosppsych.2011.06.011

7. American College of Emergency Physicians, EMTALA Fact Sheet. https://www.acep.org/life-as-a-physician/ethics--legal/emtala/emtala-fact-sheet/

8. Grzenda A. Carlat Hosp Psych Report. 2021 Jan;1(1 ):5-9

The American Gastroenterological Association has issued new guidelines for the medical treatment of irritable bowel syndrome (IBS).

The guidelines, which are separated into one publication for IBS with constipation (IBS-C) and another for IBS with diarrhea (IBS-D), are the first to advise clinicians in the usage of new, old, and over-the-counter drugs for IBS, according to a press release from the AGA.

“With more treatments available, physicians can tailor a personalized approach based on the symptoms a patient with IBS is experiencing,” AGA said.

Published simultaneously in Gastroenterology, the two guidelines describe a shared rationale for their creation, noting how the treatment landscape has changed since the AGA last issued IBS guidelines in 2014.

IBS-C

In the IBS-C guidelines, co–first authors Lin Chang, MD, AGAF, of the University of Los Angeles, and Shahnaz Sultan, MD, MHSc, AGAF, of the Minneapolis Veterans Affairs Healthcare System, noted that IBS-C accounts for “more than a third of IBS cases,” with patients frequently reporting “feeling self-conscious, avoiding sex, difficulty concentrating, [and] not feeling able to reach one’s full potential.”

They offered nine pharmacologic recommendations, eight of which are conditional, with certainty in evidence ranging from low to high.

The only strong recommendation with a high certainty in evidence is for linaclotide.

“Across four RCTs [randomized controlled trials], linaclotide improved global assessment of IBS-C symptoms (FDA responder), abdominal pain, complete spontaneous bowel movement response, as well as adequate global response,” Dr. Chang and colleagues wrote.

Conditional recommendations with moderate certainty in evidence are provided for tenapanor, plecanatide, tegaserod, and lubiprostone. Recommendations for polyethylene glycol laxatives, tricyclic antidepressants and antispasmodics are conditional and based on low-certainty evidence, as well as a conditional recommendation against selective serotonin reuptake inhibitors, also based on low-certainty evidence.

IBS-D

The IBS-D guidelines, led by co–first authors Anthony Lembo, MD, AGAF, of Beth Israel Deaconess Medical Center, Boston, and Dr. Sultan, includes eight conditional recommendations with certainty in evidence ranging from very low to moderate.

Drugs recommended based on moderate-certainty evidence include eluxadoline, alosetron, and rifaximin, with the added note that patients who respond to rifaximin but have recurrence should be treated again with rifaximin. Low-certainty evidence supported recommendations for tricyclic antidepressants, and antispasmodics. Very low–certainty evidence stands behind a recommendation for loperamide. Again, the panel made a conditional recommendation against SSRIs, also based on low-certainty evidence.
 

Shared decision-making

Both publications concluded with similar statements about the importance of shared decision-making, plus a practical mindset, in management of IBS.

“Acknowledging that multimodal treatments that include dietary and behavioral approaches in conjunction with drug therapy may provide maximal benefits and that treatment choices may be influenced by patient preferences, practitioners should engage in shared decision-making with patients when choosing the best therapy,” Dr. Lembo and colleagues wrote. “The importance of the patient-physician relationship is paramount in caring for individuals with IBS, and understanding patient preferences (for side-effect tolerability as well as cost) is valuable in choosing the right therapy.”

Both guidelines noted that some newer drugs for IBS have no generic alternative, and preauthorization may be required. Payer approval may depend on previous treatment failure with generic alternatives, they added.

The guidelines were commissioned and funded by the AGA Institute. The authors disclosed relationships with Ardelyx, Immunic, Protagonist, and others.

The American Gastroenterological Association has issued new guidelines for the medical treatment of irritable bowel syndrome (IBS).

The guidelines, which are separated into one publication for IBS with constipation (IBS-C) and another for IBS with diarrhea (IBS-D), are the first to advise clinicians in the usage of new, old, and over-the-counter drugs for IBS, according to a press release from the AGA.

“With more treatments available, physicians can tailor a personalized approach based on the symptoms a patient with IBS is experiencing,” AGA said.

Published simultaneously in Gastroenterology, the two guidelines describe a shared rationale for their creation, noting how the treatment landscape has changed since the AGA last issued IBS guidelines in 2014.

IBS-C

In the IBS-C guidelines, co–first authors Lin Chang, MD, AGAF, of the University of Los Angeles, and Shahnaz Sultan, MD, MHSc, AGAF, of the Minneapolis Veterans Affairs Healthcare System, noted that IBS-C accounts for “more than a third of IBS cases,” with patients frequently reporting “feeling self-conscious, avoiding sex, difficulty concentrating, [and] not feeling able to reach one’s full potential.”

They offered nine pharmacologic recommendations, eight of which are conditional, with certainty in evidence ranging from low to high.

The only strong recommendation with a high certainty in evidence is for linaclotide.

“Across four RCTs [randomized controlled trials], linaclotide improved global assessment of IBS-C symptoms (FDA responder), abdominal pain, complete spontaneous bowel movement response, as well as adequate global response,” Dr. Chang and colleagues wrote.

Conditional recommendations with moderate certainty in evidence are provided for tenapanor, plecanatide, tegaserod, and lubiprostone. Recommendations for polyethylene glycol laxatives, tricyclic antidepressants and antispasmodics are conditional and based on low-certainty evidence, as well as a conditional recommendation against selective serotonin reuptake inhibitors, also based on low-certainty evidence.

IBS-D

The IBS-D guidelines, led by co–first authors Anthony Lembo, MD, AGAF, of Beth Israel Deaconess Medical Center, Boston, and Dr. Sultan, includes eight conditional recommendations with certainty in evidence ranging from very low to moderate.

Drugs recommended based on moderate-certainty evidence include eluxadoline, alosetron, and rifaximin, with the added note that patients who respond to rifaximin but have recurrence should be treated again with rifaximin. Low-certainty evidence supported recommendations for tricyclic antidepressants, and antispasmodics. Very low–certainty evidence stands behind a recommendation for loperamide. Again, the panel made a conditional recommendation against SSRIs, also based on low-certainty evidence.
 

Shared decision-making

Both publications concluded with similar statements about the importance of shared decision-making, plus a practical mindset, in management of IBS.

“Acknowledging that multimodal treatments that include dietary and behavioral approaches in conjunction with drug therapy may provide maximal benefits and that treatment choices may be influenced by patient preferences, practitioners should engage in shared decision-making with patients when choosing the best therapy,” Dr. Lembo and colleagues wrote. “The importance of the patient-physician relationship is paramount in caring for individuals with IBS, and understanding patient preferences (for side-effect tolerability as well as cost) is valuable in choosing the right therapy.”

Both guidelines noted that some newer drugs for IBS have no generic alternative, and preauthorization may be required. Payer approval may depend on previous treatment failure with generic alternatives, they added.

The guidelines were commissioned and funded by the AGA Institute. The authors disclosed relationships with Ardelyx, Immunic, Protagonist, and others.

The American Gastroenterological Association has issued new guidelines for the medical treatment of irritable bowel syndrome (IBS).

The guidelines, which are separated into one publication for IBS with constipation (IBS-C) and another for IBS with diarrhea (IBS-D), are the first to advise clinicians in the usage of new, old, and over-the-counter drugs for IBS, according to a press release from the AGA.

“With more treatments available, physicians can tailor a personalized approach based on the symptoms a patient with IBS is experiencing,” AGA said.

Published simultaneously in Gastroenterology, the two guidelines describe a shared rationale for their creation, noting how the treatment landscape has changed since the AGA last issued IBS guidelines in 2014.

IBS-C

In the IBS-C guidelines, co–first authors Lin Chang, MD, AGAF, of the University of Los Angeles, and Shahnaz Sultan, MD, MHSc, AGAF, of the Minneapolis Veterans Affairs Healthcare System, noted that IBS-C accounts for “more than a third of IBS cases,” with patients frequently reporting “feeling self-conscious, avoiding sex, difficulty concentrating, [and] not feeling able to reach one’s full potential.”

They offered nine pharmacologic recommendations, eight of which are conditional, with certainty in evidence ranging from low to high.

The only strong recommendation with a high certainty in evidence is for linaclotide.

“Across four RCTs [randomized controlled trials], linaclotide improved global assessment of IBS-C symptoms (FDA responder), abdominal pain, complete spontaneous bowel movement response, as well as adequate global response,” Dr. Chang and colleagues wrote.

Conditional recommendations with moderate certainty in evidence are provided for tenapanor, plecanatide, tegaserod, and lubiprostone. Recommendations for polyethylene glycol laxatives, tricyclic antidepressants and antispasmodics are conditional and based on low-certainty evidence, as well as a conditional recommendation against selective serotonin reuptake inhibitors, also based on low-certainty evidence.

IBS-D

The IBS-D guidelines, led by co–first authors Anthony Lembo, MD, AGAF, of Beth Israel Deaconess Medical Center, Boston, and Dr. Sultan, includes eight conditional recommendations with certainty in evidence ranging from very low to moderate.

Drugs recommended based on moderate-certainty evidence include eluxadoline, alosetron, and rifaximin, with the added note that patients who respond to rifaximin but have recurrence should be treated again with rifaximin. Low-certainty evidence supported recommendations for tricyclic antidepressants, and antispasmodics. Very low–certainty evidence stands behind a recommendation for loperamide. Again, the panel made a conditional recommendation against SSRIs, also based on low-certainty evidence.
 

Shared decision-making

Both publications concluded with similar statements about the importance of shared decision-making, plus a practical mindset, in management of IBS.

“Acknowledging that multimodal treatments that include dietary and behavioral approaches in conjunction with drug therapy may provide maximal benefits and that treatment choices may be influenced by patient preferences, practitioners should engage in shared decision-making with patients when choosing the best therapy,” Dr. Lembo and colleagues wrote. “The importance of the patient-physician relationship is paramount in caring for individuals with IBS, and understanding patient preferences (for side-effect tolerability as well as cost) is valuable in choosing the right therapy.”

Both guidelines noted that some newer drugs for IBS have no generic alternative, and preauthorization may be required. Payer approval may depend on previous treatment failure with generic alternatives, they added.

The guidelines were commissioned and funded by the AGA Institute. The authors disclosed relationships with Ardelyx, Immunic, Protagonist, and others.

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 52 weeks in adolescents with inadequately controlled moderate-to-severe atopic dermatitis (AD).

Major finding: Rate of treatment emergent adverse events was 370.2 events/100 patient-years, with most being mild/moderate. At least 75% improvement in Eczema Area and Severity Index scores was achieved by 81.2% of patients receiving dupilumab at week 52 and 51.9% of patients who were uptitrated from every-4-week (q4w) to every-2-week (q2w) dosing regimen at week 48 after the first uptitration visit.

Study details: Findings are from an ongoing open-label extension study, LIBERTY AD PED-OLE, including 294 adolescents with moderate-to-severe AD who participated in previous dupilumab trials, received dupilumab q4w, and were uptitrated to the weight-tiered q2w dose regimen upon inadequate clinical response.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Eight authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and the other authors reported ties with various sources, including Sanofi and Regeneron.

Source: Blauvelt A et al. Long-term efficacy and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis: Results through week 52 from a phase III open-label extension trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022;23:365–383  (May 14). Doi: 10.1007/s40257-022-00683-2

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 52 weeks in adolescents with inadequately controlled moderate-to-severe atopic dermatitis (AD).

Major finding: Rate of treatment emergent adverse events was 370.2 events/100 patient-years, with most being mild/moderate. At least 75% improvement in Eczema Area and Severity Index scores was achieved by 81.2% of patients receiving dupilumab at week 52 and 51.9% of patients who were uptitrated from every-4-week (q4w) to every-2-week (q2w) dosing regimen at week 48 after the first uptitration visit.

Study details: Findings are from an ongoing open-label extension study, LIBERTY AD PED-OLE, including 294 adolescents with moderate-to-severe AD who participated in previous dupilumab trials, received dupilumab q4w, and were uptitrated to the weight-tiered q2w dose regimen upon inadequate clinical response.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Eight authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and the other authors reported ties with various sources, including Sanofi and Regeneron.

Source: Blauvelt A et al. Long-term efficacy and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis: Results through week 52 from a phase III open-label extension trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022;23:365–383  (May 14). Doi: 10.1007/s40257-022-00683-2

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 52 weeks in adolescents with inadequately controlled moderate-to-severe atopic dermatitis (AD).

Major finding: Rate of treatment emergent adverse events was 370.2 events/100 patient-years, with most being mild/moderate. At least 75% improvement in Eczema Area and Severity Index scores was achieved by 81.2% of patients receiving dupilumab at week 52 and 51.9% of patients who were uptitrated from every-4-week (q4w) to every-2-week (q2w) dosing regimen at week 48 after the first uptitration visit.

Study details: Findings are from an ongoing open-label extension study, LIBERTY AD PED-OLE, including 294 adolescents with moderate-to-severe AD who participated in previous dupilumab trials, received dupilumab q4w, and were uptitrated to the weight-tiered q2w dose regimen upon inadequate clinical response.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Eight authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and the other authors reported ties with various sources, including Sanofi and Regeneron.

Source: Blauvelt A et al. Long-term efficacy and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis: Results through week 52 from a phase III open-label extension trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022;23:365–383  (May 14). Doi: 10.1007/s40257-022-00683-2

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

[email protected]

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

[email protected]

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

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A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

copyright nebari/Thinkstock

“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

copyright nebari/Thinkstock

“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

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“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

The Diagnosis: Granuloma Annulare

A biopsy of a lesion on the right flank demonstrated granulomatous inflammation and interstitial mucin (Figure), characteristic of granuloma annulare (GA).^1,2 Granuloma annulare is a relatively common skin disorder with an unknown etiology. It typically presents as smooth, annular, erythematous plaques.¹ The most common variants of GA are localized, generalized, and subcutaneous. Our case demonstrated Wolf isotopic response, an unrelated skin disease that forms at the same location as a previously healed skin lesion.² It is important to be aware of this phenomenon so that it is not confused with a recurrence of herpes zoster virus (HZV).

Although relatively infrequent, GA is the most common isotopic response following HZV infections.^3-5 Other postherpetic isotopic eruptions include cutaneous malignancies, lichen planus, sarcoidosis, morphea, reactive perforating collagenosis, psoriasis, and infections, among others.^3,5,6 The time between HZV infection and GA can be variable, ranging from a few weeks to many years apart.³

Oftentimes GA will spontaneously resolve within 2 years; however, recurrence is common.^7-9 There currently are no standard treatment guidelines. The most promising treatment options include intralesional or topical glucocorticoids for localized GA as well as phototherapy or hydroxychloroquine for widespread disease.^8,10  

Annular elastolytic giant cell granuloma (also called actinic granuloma) is a rare idiopathic inflammatory skin disease. It is characterized by erythematous annular papules or plaques mainly found on sun-exposed skin, such as the backs of the hands, forearms, or face.^11,12 Therefore, based on the distribution of our patient’s lesions, annular elastolytic giant cell granuloma was an unlikely diagnosis. Furthermore, it is not a known postherpetic isotopic reaction. Annular elastolytic giant cell granuloma can appear histologically similar to GA. Differentiating histologic features include a nonpalisading granuloma as well as the absence of mucin and necrobiosis.¹²

Annular lichen planus is a long-recognized but uncommon clinical variant of lichen planus that typically presents as pruritic, purple, annular plaques on the penis, scrotum, or intertriginous areas.¹³ The violaceous coloring is more characteristic of lichen planus. Histology is helpful in differentiating from GA.

Nummular eczema presents as scattered, welldefined, pruritic, erythematous, coin-shaped, coin-sized plaques in patients with diffusely dry skin.¹⁴ The scaling and serous crusting as well as more prominent pruritus help distinguish it from GA. The appearance of nummular eczema is quite characteristic; therefore, a biopsy typically is unnecessary for diagnosis. However, a potassium hydroxide wet mount examination of a skin scraping should be performed if tinea corporis also is suspected.

Superficial erythema annulare centrifugum classically presents as an annular or arciform pruritic lesion with an advancing outer erythematous edge with an inner rim of scale that most commonly occurs on the lower extremities. ¹⁵ The presence of pruritus and trailing scale helps distinguish this lesion from GA. Histologically, there are epidermal changes of hyperplasia, spongiosis, and parakeratosis, as well as lymphohistiocytic infiltrate surrounding the superficial dermal vessels^.16

We report this case to highlight GA as the most common postherpetic isotopic response. It should be on the differential diagnosis when a patient presents with erythematous, smooth, annular plaques occurring in the distribution of a resolved case of HZV.

Key clinical point: Adagrasib shows favorable clinical efficacy without any new safety signals in patients with previously treated KRAS^G12C-mutated nonsmall cell lung cancer (NSCLC).

Major finding: Among patients with measurable disease at baseline, 42.9% had a confirmed objective response. The median progression-free survival was 6.5 (95% CI 4.7-8.4) months. At a median follow-up of 15.6 months, the median overall survival was 12.6 (95% CI 9.2-19.2) months. The treatment-related adverse events of grade 1/2 and 3 occurred in 52.6% and 44.8% of patients, respectively.

Study details: This registrational phase 2 cohort study investigated adagrasib in 116 patients with KRAS^G12C-mutated NSCLC previously treated with platinum-based chemotherapy with or without anti-programmed death 1 or programmed death ligand 1 therapy.

Disclosures: The study was funded by Mirati Therapeutics. The authors reported ties with one or more pharmaceutical companies, including employment or stock options in Mirati Therapeutics.

Source: Jänne PA et al. Adagrasib in non–small-cell lung cancer harboring a KRAS^G12Cmutation. N Engl J Med. 2022 (Jun 3). Doi: 10.1056/NEJMoa2204619

Key clinical point: Adagrasib shows favorable clinical efficacy without any new safety signals in patients with previously treated KRAS^G12C-mutated nonsmall cell lung cancer (NSCLC).

Major finding: Among patients with measurable disease at baseline, 42.9% had a confirmed objective response. The median progression-free survival was 6.5 (95% CI 4.7-8.4) months. At a median follow-up of 15.6 months, the median overall survival was 12.6 (95% CI 9.2-19.2) months. The treatment-related adverse events of grade 1/2 and 3 occurred in 52.6% and 44.8% of patients, respectively.

Study details: This registrational phase 2 cohort study investigated adagrasib in 116 patients with KRAS^G12C-mutated NSCLC previously treated with platinum-based chemotherapy with or without anti-programmed death 1 or programmed death ligand 1 therapy.

Disclosures: The study was funded by Mirati Therapeutics. The authors reported ties with one or more pharmaceutical companies, including employment or stock options in Mirati Therapeutics.

Source: Jänne PA et al. Adagrasib in non–small-cell lung cancer harboring a KRAS^G12Cmutation. N Engl J Med. 2022 (Jun 3). Doi: 10.1056/NEJMoa2204619

Key clinical point: Adagrasib shows favorable clinical efficacy without any new safety signals in patients with previously treated KRAS^G12C-mutated nonsmall cell lung cancer (NSCLC).

Major finding: Among patients with measurable disease at baseline, 42.9% had a confirmed objective response. The median progression-free survival was 6.5 (95% CI 4.7-8.4) months. At a median follow-up of 15.6 months, the median overall survival was 12.6 (95% CI 9.2-19.2) months. The treatment-related adverse events of grade 1/2 and 3 occurred in 52.6% and 44.8% of patients, respectively.

Study details: This registrational phase 2 cohort study investigated adagrasib in 116 patients with KRAS^G12C-mutated NSCLC previously treated with platinum-based chemotherapy with or without anti-programmed death 1 or programmed death ligand 1 therapy.

Disclosures: The study was funded by Mirati Therapeutics. The authors reported ties with one or more pharmaceutical companies, including employment or stock options in Mirati Therapeutics.

Source: Jänne PA et al. Adagrasib in non–small-cell lung cancer harboring a KRAS^G12Cmutation. N Engl J Med. 2022 (Jun 3). Doi: 10.1056/NEJMoa2204619

Key clinical point: Cemiplimab appears to have the most favorable benefit-risk ratio among the analyzed immune checkpoint inhibitors (ICI) for the treatment of patients with nonsmall cell lung cancer (NSCLC).

Major finding: Cemiplimab was associated with the lowest hazard ratio (HR) for overall survival (OS) relative to chemotherapy (HR 0.68; 95% CI 0. 57-0.81), translating to the highest surface under the cumulative ranking curve (SUCRA) value of 49.5%. Additionally, cemiplimab was associated with the lowest incidence of treatment-related adverse events (TRAE) relative to chemotherapy (odds ratio 0.17; 95% credible interval 0.06-0.45).

Study details: The data come from a network meta-analysis of 13 randomized controlled trials (n = 7795). The SUCRA values of all ICI (cemiplimab, avelumab, atezolizumab, nivolumab, and pembrolizumab) were determined for OS and TRAE.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jiang M et al. Comparative efficacy and safety of anti-PD-1/PD-L1 for the treatment of non-small cell lung cancer: A network meta-analysis of 13 randomized controlled studies. Front Oncol. 2022;12:827050 (May 10). Doi: 10.3389/fonc.2022.827050

Key clinical point: Cemiplimab appears to have the most favorable benefit-risk ratio among the analyzed immune checkpoint inhibitors (ICI) for the treatment of patients with nonsmall cell lung cancer (NSCLC).

Major finding: Cemiplimab was associated with the lowest hazard ratio (HR) for overall survival (OS) relative to chemotherapy (HR 0.68; 95% CI 0. 57-0.81), translating to the highest surface under the cumulative ranking curve (SUCRA) value of 49.5%. Additionally, cemiplimab was associated with the lowest incidence of treatment-related adverse events (TRAE) relative to chemotherapy (odds ratio 0.17; 95% credible interval 0.06-0.45).

Study details: The data come from a network meta-analysis of 13 randomized controlled trials (n = 7795). The SUCRA values of all ICI (cemiplimab, avelumab, atezolizumab, nivolumab, and pembrolizumab) were determined for OS and TRAE.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jiang M et al. Comparative efficacy and safety of anti-PD-1/PD-L1 for the treatment of non-small cell lung cancer: A network meta-analysis of 13 randomized controlled studies. Front Oncol. 2022;12:827050 (May 10). Doi: 10.3389/fonc.2022.827050

Key clinical point: Cemiplimab appears to have the most favorable benefit-risk ratio among the analyzed immune checkpoint inhibitors (ICI) for the treatment of patients with nonsmall cell lung cancer (NSCLC).

Major finding: Cemiplimab was associated with the lowest hazard ratio (HR) for overall survival (OS) relative to chemotherapy (HR 0.68; 95% CI 0. 57-0.81), translating to the highest surface under the cumulative ranking curve (SUCRA) value of 49.5%. Additionally, cemiplimab was associated with the lowest incidence of treatment-related adverse events (TRAE) relative to chemotherapy (odds ratio 0.17; 95% credible interval 0.06-0.45).

Study details: The data come from a network meta-analysis of 13 randomized controlled trials (n = 7795). The SUCRA values of all ICI (cemiplimab, avelumab, atezolizumab, nivolumab, and pembrolizumab) were determined for OS and TRAE.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jiang M et al. Comparative efficacy and safety of anti-PD-1/PD-L1 for the treatment of non-small cell lung cancer: A network meta-analysis of 13 randomized controlled studies. Front Oncol. 2022;12:827050 (May 10). Doi: 10.3389/fonc.2022.827050