Many dermatologists favor using either needles or cannulas for dermal filler treatments, but there’s a role for both instruments, according to Terrence Keaney, MD.

FlamingoImages/iStock/Getty Images

“You may be a needle person or a cannula person, but it doesn’t have to be that way,” he said during the Orlando Dermatology Aesthetic and Clinical Conference. “There are pros and cons of both techniques, but I think there’s a place for both.”

Such emerging data present a conundrum, though. If someone is comfortable injecting dermal filler with needles, why switch to using cannulas? After all, a case study reported arterial penetration with blunt-tipped cannulas using injectables . “Cannulas are not 100% safe,” Dr. Keaney said. “One of my mentors once said, “If a vascular event has not happened to you yet, you have not injected enough. These things can happen even in the most experienced hands, whether you use a needle or a cannula.”

However, safety data from a recently published retrospective study demonstrated that cannulas are less likely to be associated with occlusions compared with needles (a risk of 1 occlusion per 40,882 injections vs. 1 occlusion per 6,410 injections (P less than .001) (JAMA Dermatol. 2021 Feb 1;157[2]:174-80).

“Cannulas are generally safer because the blunt tip kind of dissects tissue and pushes vessels away,” he said. “That doesn’t mean it can’t get into a vessel, it just requires greater force to penetrate facial arteries with a cannula. Finer tips may be easier to use.”

Larger cannulas can tear into an arterial wall when the artery wall is relatively fixed, so it cannot slide aside enough to avoid injury, Dr. Keaney continued. “Arterial location perpendicular to cannula trajectory carries the most risk,” he said. Meanwhile, filler-induced blindness, which he characterized as “the worst possible outcome,” is often due to the retrograde embolization of the product. This can occur with injection pressures greater than the sum of the systolic arterial pressure and the frictional forces due to viscous flow.

Dr. Keaney said he uses both needles and cannulas in his clinical practice. “I use a needle to inject on bone if I want to mimic bony projections along the zygomatic arch or jawline or chin,” he said. “I think a needle can get those boluses to develop that projection that you want. If I’m injecting within soft tissue plane, I use a 22 G cannula and keep the cannula moving within the tissue. I inject slowly and less than 0.2 cc per bolus. I compress when injecting on the nose and I’m cautious to inject previous patients who have undergone plastic surgery or in areas of previous scarring.”

Dr. Keaney reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies.

[email protected]

Many dermatologists favor using either needles or cannulas for dermal filler treatments, but there’s a role for both instruments, according to Terrence Keaney, MD.

FlamingoImages/iStock/Getty Images

“You may be a needle person or a cannula person, but it doesn’t have to be that way,” he said during the Orlando Dermatology Aesthetic and Clinical Conference. “There are pros and cons of both techniques, but I think there’s a place for both.”

Such emerging data present a conundrum, though. If someone is comfortable injecting dermal filler with needles, why switch to using cannulas? After all, a case study reported arterial penetration with blunt-tipped cannulas using injectables . “Cannulas are not 100% safe,” Dr. Keaney said. “One of my mentors once said, “If a vascular event has not happened to you yet, you have not injected enough. These things can happen even in the most experienced hands, whether you use a needle or a cannula.”

However, safety data from a recently published retrospective study demonstrated that cannulas are less likely to be associated with occlusions compared with needles (a risk of 1 occlusion per 40,882 injections vs. 1 occlusion per 6,410 injections (P less than .001) (JAMA Dermatol. 2021 Feb 1;157[2]:174-80).

“Cannulas are generally safer because the blunt tip kind of dissects tissue and pushes vessels away,” he said. “That doesn’t mean it can’t get into a vessel, it just requires greater force to penetrate facial arteries with a cannula. Finer tips may be easier to use.”

Larger cannulas can tear into an arterial wall when the artery wall is relatively fixed, so it cannot slide aside enough to avoid injury, Dr. Keaney continued. “Arterial location perpendicular to cannula trajectory carries the most risk,” he said. Meanwhile, filler-induced blindness, which he characterized as “the worst possible outcome,” is often due to the retrograde embolization of the product. This can occur with injection pressures greater than the sum of the systolic arterial pressure and the frictional forces due to viscous flow.

Dr. Keaney said he uses both needles and cannulas in his clinical practice. “I use a needle to inject on bone if I want to mimic bony projections along the zygomatic arch or jawline or chin,” he said. “I think a needle can get those boluses to develop that projection that you want. If I’m injecting within soft tissue plane, I use a 22 G cannula and keep the cannula moving within the tissue. I inject slowly and less than 0.2 cc per bolus. I compress when injecting on the nose and I’m cautious to inject previous patients who have undergone plastic surgery or in areas of previous scarring.”

Dr. Keaney reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies.

[email protected]

Many dermatologists favor using either needles or cannulas for dermal filler treatments, but there’s a role for both instruments, according to Terrence Keaney, MD.

FlamingoImages/iStock/Getty Images

“You may be a needle person or a cannula person, but it doesn’t have to be that way,” he said during the Orlando Dermatology Aesthetic and Clinical Conference. “There are pros and cons of both techniques, but I think there’s a place for both.”

Such emerging data present a conundrum, though. If someone is comfortable injecting dermal filler with needles, why switch to using cannulas? After all, a case study reported arterial penetration with blunt-tipped cannulas using injectables . “Cannulas are not 100% safe,” Dr. Keaney said. “One of my mentors once said, “If a vascular event has not happened to you yet, you have not injected enough. These things can happen even in the most experienced hands, whether you use a needle or a cannula.”

However, safety data from a recently published retrospective study demonstrated that cannulas are less likely to be associated with occlusions compared with needles (a risk of 1 occlusion per 40,882 injections vs. 1 occlusion per 6,410 injections (P less than .001) (JAMA Dermatol. 2021 Feb 1;157[2]:174-80).

“Cannulas are generally safer because the blunt tip kind of dissects tissue and pushes vessels away,” he said. “That doesn’t mean it can’t get into a vessel, it just requires greater force to penetrate facial arteries with a cannula. Finer tips may be easier to use.”

Larger cannulas can tear into an arterial wall when the artery wall is relatively fixed, so it cannot slide aside enough to avoid injury, Dr. Keaney continued. “Arterial location perpendicular to cannula trajectory carries the most risk,” he said. Meanwhile, filler-induced blindness, which he characterized as “the worst possible outcome,” is often due to the retrograde embolization of the product. This can occur with injection pressures greater than the sum of the systolic arterial pressure and the frictional forces due to viscous flow.

Dr. Keaney said he uses both needles and cannulas in his clinical practice. “I use a needle to inject on bone if I want to mimic bony projections along the zygomatic arch or jawline or chin,” he said. “I think a needle can get those boluses to develop that projection that you want. If I’m injecting within soft tissue plane, I use a 22 G cannula and keep the cannula moving within the tissue. I inject slowly and less than 0.2 cc per bolus. I compress when injecting on the nose and I’m cautious to inject previous patients who have undergone plastic surgery or in areas of previous scarring.”

Dr. Keaney reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies.

[email protected]

For many adults, depression and chronic medical conditions are inextricably linked.

In fact, the prevalence of depression is 2-10 times higher among people with chronic medical conditions, particularly in people with chronic pain, where the prevalence reaches 40%-60%, according to Jonathan E. Alpert, MD, PhD.

“About 60% of adults over 65 have two or more chronic conditions, of which depression is the single most common comorbidity,” Dr. Alpert, chair of the department of psychiatry and behavioral sciences at the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Premorbid depression is a risk factor for a number of medical conditions, such as heart disease. We also know that medical illness is a risk factor for depression. Comorbid depression predicts poorer health outcomes, including disability, hospital readmission, and mortality. It is also associated with up to severalfold higher general medical costs.”

Despite the pervasive nature of depression on other medical conditions, a limited evidence base exists to guide clinicians on treatment approaches.

“Most major depressive disorder randomized clinical trials exclude individuals with active medical illness, but we do know that medical comorbidity is associated with poorer depression outcomes,” Dr. Alpert said. For example, the STAR*D trial found that people with major depressive disorder plus medical comorbidity had lower remission rates, compared with those who had MDD alone (P < .001), while a large analysis from University of Pittsburgh researchers found that people with medical comorbidities had higher depression recurrence rates.

An assessment of the relationship between medical conditions and depression should include thinking about the association between the medical illness itself and medications with depressive symptoms.

“Are the medications contributing to depressive symptoms?” he asked. “We also want to be thinking of the impact of medical illness and medications on antidepressant pharmacokinetics and pharmacodynamics. We also want to know about the evidence for antidepressant safety, tolerability, efficacy, and anticipated drug-drug interactions among individuals with the medical illness. You also want to enhance focus on treatment adherence and coordination of care.”

Nontraditional routes of antidepressant administration exist for patients who have difficulty swallowing pills. Food and Drug Administration–approved options include transdermal selegiline; intranasal esketamine; liquid forms of fluoxetine, escitalopram, paroxetine, nortriptyline, doxepin, imipramine, and lithium; and oral disintegrating tablet forms of mirtazapine and selegiline. As for non–FDA-approved forms of antidepressant administration, small studies or case reports have appeared in the medical literature regarding intravenous ketamine, citalopram, amitriptyline, mirtazapine, maprotiline, and lithium; intramuscular ketamine and amitriptyline; and rectal forms of antidepressants such as trazodone, amitriptyline, doxepin, fluoxetine, and lamotrigine.

“It’s good to keep in mind that, when you’re not able to use by mouth antidepressants or typical tablet forms of antidepressants, there are other options available,” said Dr. Alpert, who is also chair of the American Psychiatric Association’s Council on Research.

Metabolism of medications occurs primarily in the liver, he continued, but some metabolic enzymes also line the intestinal tract. The metabolism of a substrate may be inhibited or induced by other drugs.

“If someone is on drug A and we give drug B, and drug B is inhibiting the metabolism of drug A, there will be a very rapid impact – hours to just a few days,” Dr. Alpert said. “The substrate levels rise very quickly, so within hours or days of taking drug B, drug A levels can rise steeply.” On the other hand, if someone is on drug A and you give a drug B – which induces the enzymes that usually metabolize drug A – the impact will be gradual. “That’s because induction requires increased synthesis of the metabolic enzyme responsible for metabolizing drug A,” he said. “That happens over days to weeks.”

Medications that are potential inducers of metabolism include carbamazepine, phenobarbital, phenytoin, primidone, prednisone, ritonavir, rifampin, chronic alcohol use, chronic smoking, St. John’s wort, and consumption of large quantities of cruciferous vegetables and charbroiled meats.

On the other hand, potential inhibitors of metabolism include antifungals, macrolide antibiotics, fluoroquinolones, antiretrovirals, isoniazid, antimalarials, disulfiram, SSRIs, phenothiazines, valproic acid, nefazodone, duloxetine, bupropion, beta-blockers, acute alcohol use, cimetidine, quinidine, calcium channel blockers, grapefruit juice, propafenone, and amiodarone.

“When treating people with significant medical comorbidity, start low and go slow, but persevere,” Dr. Alpert advised. “We want to always think about the risk of treating versus the risk of not treating, or not treating actively enough. Often, people with comorbid medical illness require the same or even more assertive treatment with pharmacotherapy for their depression as people without medical illness. So, we don’t want to make the mistake of undertreating depression. We also want to anticipate and address challenges with adherence.”

He also recommended being mindful of the most salient side effects for a given condition, such as lowered seizure threshold or QT prolongation in populations with brain injury or with cardiovascular disease, and to leverage dual benefits when they might exist, such as using [selective norepinephrine reuptake inhibitors] for depression and pain or hot flashes, or bupropion for depression and smoking cessation, or mirtazapine, which is effective for nausea, cachexia, or insomnia, as well as depression itself.

“We want to collaborate closely and regularly with other treaters, sharing our notes and diagnostic impressions,” Dr. Alpert said. “We want to use all the tools in the box in addition to pharmacotherapy, thinking about psychotherapy, neuromodulation, and peer navigators. We want to strive for measurement-based care using rating scales when we can, to augment our treatment. And we want to be resourceful. There are very few absolute contraindications in treating the medically ill.”

Dr. Alpert reports having received speaker’s honoraria, consulting fees, and research support from numerous pharmaceutical companies.

[email protected]

For many adults, depression and chronic medical conditions are inextricably linked.

In fact, the prevalence of depression is 2-10 times higher among people with chronic medical conditions, particularly in people with chronic pain, where the prevalence reaches 40%-60%, according to Jonathan E. Alpert, MD, PhD.

“About 60% of adults over 65 have two or more chronic conditions, of which depression is the single most common comorbidity,” Dr. Alpert, chair of the department of psychiatry and behavioral sciences at the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Premorbid depression is a risk factor for a number of medical conditions, such as heart disease. We also know that medical illness is a risk factor for depression. Comorbid depression predicts poorer health outcomes, including disability, hospital readmission, and mortality. It is also associated with up to severalfold higher general medical costs.”

Despite the pervasive nature of depression on other medical conditions, a limited evidence base exists to guide clinicians on treatment approaches.

“Most major depressive disorder randomized clinical trials exclude individuals with active medical illness, but we do know that medical comorbidity is associated with poorer depression outcomes,” Dr. Alpert said. For example, the STAR*D trial found that people with major depressive disorder plus medical comorbidity had lower remission rates, compared with those who had MDD alone (P < .001), while a large analysis from University of Pittsburgh researchers found that people with medical comorbidities had higher depression recurrence rates.

An assessment of the relationship between medical conditions and depression should include thinking about the association between the medical illness itself and medications with depressive symptoms.

“Are the medications contributing to depressive symptoms?” he asked. “We also want to be thinking of the impact of medical illness and medications on antidepressant pharmacokinetics and pharmacodynamics. We also want to know about the evidence for antidepressant safety, tolerability, efficacy, and anticipated drug-drug interactions among individuals with the medical illness. You also want to enhance focus on treatment adherence and coordination of care.”

Nontraditional routes of antidepressant administration exist for patients who have difficulty swallowing pills. Food and Drug Administration–approved options include transdermal selegiline; intranasal esketamine; liquid forms of fluoxetine, escitalopram, paroxetine, nortriptyline, doxepin, imipramine, and lithium; and oral disintegrating tablet forms of mirtazapine and selegiline. As for non–FDA-approved forms of antidepressant administration, small studies or case reports have appeared in the medical literature regarding intravenous ketamine, citalopram, amitriptyline, mirtazapine, maprotiline, and lithium; intramuscular ketamine and amitriptyline; and rectal forms of antidepressants such as trazodone, amitriptyline, doxepin, fluoxetine, and lamotrigine.

“It’s good to keep in mind that, when you’re not able to use by mouth antidepressants or typical tablet forms of antidepressants, there are other options available,” said Dr. Alpert, who is also chair of the American Psychiatric Association’s Council on Research.

Metabolism of medications occurs primarily in the liver, he continued, but some metabolic enzymes also line the intestinal tract. The metabolism of a substrate may be inhibited or induced by other drugs.

“If someone is on drug A and we give drug B, and drug B is inhibiting the metabolism of drug A, there will be a very rapid impact – hours to just a few days,” Dr. Alpert said. “The substrate levels rise very quickly, so within hours or days of taking drug B, drug A levels can rise steeply.” On the other hand, if someone is on drug A and you give a drug B – which induces the enzymes that usually metabolize drug A – the impact will be gradual. “That’s because induction requires increased synthesis of the metabolic enzyme responsible for metabolizing drug A,” he said. “That happens over days to weeks.”

Medications that are potential inducers of metabolism include carbamazepine, phenobarbital, phenytoin, primidone, prednisone, ritonavir, rifampin, chronic alcohol use, chronic smoking, St. John’s wort, and consumption of large quantities of cruciferous vegetables and charbroiled meats.

On the other hand, potential inhibitors of metabolism include antifungals, macrolide antibiotics, fluoroquinolones, antiretrovirals, isoniazid, antimalarials, disulfiram, SSRIs, phenothiazines, valproic acid, nefazodone, duloxetine, bupropion, beta-blockers, acute alcohol use, cimetidine, quinidine, calcium channel blockers, grapefruit juice, propafenone, and amiodarone.

“When treating people with significant medical comorbidity, start low and go slow, but persevere,” Dr. Alpert advised. “We want to always think about the risk of treating versus the risk of not treating, or not treating actively enough. Often, people with comorbid medical illness require the same or even more assertive treatment with pharmacotherapy for their depression as people without medical illness. So, we don’t want to make the mistake of undertreating depression. We also want to anticipate and address challenges with adherence.”

He also recommended being mindful of the most salient side effects for a given condition, such as lowered seizure threshold or QT prolongation in populations with brain injury or with cardiovascular disease, and to leverage dual benefits when they might exist, such as using [selective norepinephrine reuptake inhibitors] for depression and pain or hot flashes, or bupropion for depression and smoking cessation, or mirtazapine, which is effective for nausea, cachexia, or insomnia, as well as depression itself.

“We want to collaborate closely and regularly with other treaters, sharing our notes and diagnostic impressions,” Dr. Alpert said. “We want to use all the tools in the box in addition to pharmacotherapy, thinking about psychotherapy, neuromodulation, and peer navigators. We want to strive for measurement-based care using rating scales when we can, to augment our treatment. And we want to be resourceful. There are very few absolute contraindications in treating the medically ill.”

Dr. Alpert reports having received speaker’s honoraria, consulting fees, and research support from numerous pharmaceutical companies.

[email protected]

For many adults, depression and chronic medical conditions are inextricably linked.

In fact, the prevalence of depression is 2-10 times higher among people with chronic medical conditions, particularly in people with chronic pain, where the prevalence reaches 40%-60%, according to Jonathan E. Alpert, MD, PhD.

“About 60% of adults over 65 have two or more chronic conditions, of which depression is the single most common comorbidity,” Dr. Alpert, chair of the department of psychiatry and behavioral sciences at the Montefiore Medical Center and Albert Einstein College of Medicine, both in New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Premorbid depression is a risk factor for a number of medical conditions, such as heart disease. We also know that medical illness is a risk factor for depression. Comorbid depression predicts poorer health outcomes, including disability, hospital readmission, and mortality. It is also associated with up to severalfold higher general medical costs.”

Despite the pervasive nature of depression on other medical conditions, a limited evidence base exists to guide clinicians on treatment approaches.

“Most major depressive disorder randomized clinical trials exclude individuals with active medical illness, but we do know that medical comorbidity is associated with poorer depression outcomes,” Dr. Alpert said. For example, the STAR*D trial found that people with major depressive disorder plus medical comorbidity had lower remission rates, compared with those who had MDD alone (P < .001), while a large analysis from University of Pittsburgh researchers found that people with medical comorbidities had higher depression recurrence rates.

An assessment of the relationship between medical conditions and depression should include thinking about the association between the medical illness itself and medications with depressive symptoms.

“Are the medications contributing to depressive symptoms?” he asked. “We also want to be thinking of the impact of medical illness and medications on antidepressant pharmacokinetics and pharmacodynamics. We also want to know about the evidence for antidepressant safety, tolerability, efficacy, and anticipated drug-drug interactions among individuals with the medical illness. You also want to enhance focus on treatment adherence and coordination of care.”

Nontraditional routes of antidepressant administration exist for patients who have difficulty swallowing pills. Food and Drug Administration–approved options include transdermal selegiline; intranasal esketamine; liquid forms of fluoxetine, escitalopram, paroxetine, nortriptyline, doxepin, imipramine, and lithium; and oral disintegrating tablet forms of mirtazapine and selegiline. As for non–FDA-approved forms of antidepressant administration, small studies or case reports have appeared in the medical literature regarding intravenous ketamine, citalopram, amitriptyline, mirtazapine, maprotiline, and lithium; intramuscular ketamine and amitriptyline; and rectal forms of antidepressants such as trazodone, amitriptyline, doxepin, fluoxetine, and lamotrigine.

“It’s good to keep in mind that, when you’re not able to use by mouth antidepressants or typical tablet forms of antidepressants, there are other options available,” said Dr. Alpert, who is also chair of the American Psychiatric Association’s Council on Research.

Metabolism of medications occurs primarily in the liver, he continued, but some metabolic enzymes also line the intestinal tract. The metabolism of a substrate may be inhibited or induced by other drugs.

“If someone is on drug A and we give drug B, and drug B is inhibiting the metabolism of drug A, there will be a very rapid impact – hours to just a few days,” Dr. Alpert said. “The substrate levels rise very quickly, so within hours or days of taking drug B, drug A levels can rise steeply.” On the other hand, if someone is on drug A and you give a drug B – which induces the enzymes that usually metabolize drug A – the impact will be gradual. “That’s because induction requires increased synthesis of the metabolic enzyme responsible for metabolizing drug A,” he said. “That happens over days to weeks.”

Medications that are potential inducers of metabolism include carbamazepine, phenobarbital, phenytoin, primidone, prednisone, ritonavir, rifampin, chronic alcohol use, chronic smoking, St. John’s wort, and consumption of large quantities of cruciferous vegetables and charbroiled meats.

On the other hand, potential inhibitors of metabolism include antifungals, macrolide antibiotics, fluoroquinolones, antiretrovirals, isoniazid, antimalarials, disulfiram, SSRIs, phenothiazines, valproic acid, nefazodone, duloxetine, bupropion, beta-blockers, acute alcohol use, cimetidine, quinidine, calcium channel blockers, grapefruit juice, propafenone, and amiodarone.

“When treating people with significant medical comorbidity, start low and go slow, but persevere,” Dr. Alpert advised. “We want to always think about the risk of treating versus the risk of not treating, or not treating actively enough. Often, people with comorbid medical illness require the same or even more assertive treatment with pharmacotherapy for their depression as people without medical illness. So, we don’t want to make the mistake of undertreating depression. We also want to anticipate and address challenges with adherence.”

He also recommended being mindful of the most salient side effects for a given condition, such as lowered seizure threshold or QT prolongation in populations with brain injury or with cardiovascular disease, and to leverage dual benefits when they might exist, such as using [selective norepinephrine reuptake inhibitors] for depression and pain or hot flashes, or bupropion for depression and smoking cessation, or mirtazapine, which is effective for nausea, cachexia, or insomnia, as well as depression itself.

“We want to collaborate closely and regularly with other treaters, sharing our notes and diagnostic impressions,” Dr. Alpert said. “We want to use all the tools in the box in addition to pharmacotherapy, thinking about psychotherapy, neuromodulation, and peer navigators. We want to strive for measurement-based care using rating scales when we can, to augment our treatment. And we want to be resourceful. There are very few absolute contraindications in treating the medically ill.”

Dr. Alpert reports having received speaker’s honoraria, consulting fees, and research support from numerous pharmaceutical companies.

[email protected]

Common themes run through rural communities and their health needs, yet the rurality of our nation is quite diverse. Approximately 97% of the United States is rural, and yet there is no silver bullet to resolve the health disparities that exist between urban and rural America. Differences in economic condition, infrastructure, education, racial diversity, health habits, and job opportunities contribute to the health disparities seen in rural communities.

In this issue of the Journal of Hospital Medicine, Gutierrez and colleagues¹ evaluate the implementation and outcomes of a rural telehospitalist program. In a hub-and-spoke fashion, providers at a large tertiary care hospital utilized telemedicine to round on patients with an onsite advanced practice provider at a 10-bed critical access hospital. Outcomes were examined during pre- and postimplementation periods using quantitative metrics (length of stay [LOS], readmission rate, mortality, and satisfaction) and qualitative measures based on interviews with staff. LOS was reduced in the postimplementation period, with a lower but nonsignificant readmission rate and no difference in mortality. Overall satisfaction was high, although respondents noted significant communication and technology issues. This study helps broaden telemedicine research and opens the conversation on barriers in rural implementation. 

As we increasingly focus on the provision and financing of care aimed at the health of populations, the diverse issues facing rural America remain insufficiently addressed. Probst and colleagues² suggest that population-based health policies are biased toward large urban centers. Innovations to transcend this “structural urbanism” are still fraught with obstacles, as revealed during the 2020 public health emergency (PHE). Telemedicine, once thought the solution to rural health provider shortages, has not escaped structural urbanism. Prior to the PHE, Medicare did not cover many core services delivered via telehealth, including hospitalist service codes. Waivers during the PHE have temporarily opened up reimbursement pathways. Unlike most telehospitalist services, Gutierrez and colleagues did not face these payment barriers in their study. Without claims data to inform payors on the adequacy of such services, health systems remain unable to promote telemedicine as a solution to rural access and cost issues. For example, in 2018, Yu and colleagues³ described the state of telemedicine in Minnesota, again, without claims data to inform supply or demand for hospitalist services.

Beyond payment barriers, technology issues are a challenge to rural telemedicine. Access to affordable, simple, and reliable equipment and broadband internet is key to user satisfaction. In April 2020, the Federal Communications Commission estimated that 18 million Americans had insufficient access to broadband internet.⁴ This number points to the technological hurdles of rural telemedicine. 

Medicine, a highly relationship-based “team sport,” is another barrier to successful implementation. Whether serving as supervisor or primary attending (as noted in the evaluation by JaKa and colleagues⁵), the telehospitalist must be “on stage” for both patients and remote spoke colleagues. In our experience, telehospitalists also practice in-person daytime hospital medicine at spoke sites; this further enhances their relationship and connection with the spoke community and likely contributes to high satisfaction by hub hospitalists and spoke patients and nurses. 

These factors create a clear impetus for further evaluation of rural telemedicine programs. There is an extensive range of program structures to evaluate, from cross-coverage to a 24/7 virtual hospital. Satisfaction is also relative and must contextualize quantitative measurement to historic care models. The execution of a telehospitalist program should align with the goals and objectives of spoke hospitals, as satisfaction will reflect how well hub hospitalists are able to meet those needs. Thus, multicenter studies that examine commercial financial pressures and encompass a variety of patient populations are imperative.

A hub-and-spoke telemedicine program can be a crucial resource for rural hospitals. The foundation of this model revolves around key factors, including reliable financing, access to technology, seamless communication, and engendering satisfaction among providers, staff, and patients. Research must continue for these programs to overcome the financial and structural challenges to their success.

Common themes run through rural communities and their health needs, yet the rurality of our nation is quite diverse. Approximately 97% of the United States is rural, and yet there is no silver bullet to resolve the health disparities that exist between urban and rural America. Differences in economic condition, infrastructure, education, racial diversity, health habits, and job opportunities contribute to the health disparities seen in rural communities.

In this issue of the Journal of Hospital Medicine, Gutierrez and colleagues¹ evaluate the implementation and outcomes of a rural telehospitalist program. In a hub-and-spoke fashion, providers at a large tertiary care hospital utilized telemedicine to round on patients with an onsite advanced practice provider at a 10-bed critical access hospital. Outcomes were examined during pre- and postimplementation periods using quantitative metrics (length of stay [LOS], readmission rate, mortality, and satisfaction) and qualitative measures based on interviews with staff. LOS was reduced in the postimplementation period, with a lower but nonsignificant readmission rate and no difference in mortality. Overall satisfaction was high, although respondents noted significant communication and technology issues. This study helps broaden telemedicine research and opens the conversation on barriers in rural implementation. 

As we increasingly focus on the provision and financing of care aimed at the health of populations, the diverse issues facing rural America remain insufficiently addressed. Probst and colleagues² suggest that population-based health policies are biased toward large urban centers. Innovations to transcend this “structural urbanism” are still fraught with obstacles, as revealed during the 2020 public health emergency (PHE). Telemedicine, once thought the solution to rural health provider shortages, has not escaped structural urbanism. Prior to the PHE, Medicare did not cover many core services delivered via telehealth, including hospitalist service codes. Waivers during the PHE have temporarily opened up reimbursement pathways. Unlike most telehospitalist services, Gutierrez and colleagues did not face these payment barriers in their study. Without claims data to inform payors on the adequacy of such services, health systems remain unable to promote telemedicine as a solution to rural access and cost issues. For example, in 2018, Yu and colleagues³ described the state of telemedicine in Minnesota, again, without claims data to inform supply or demand for hospitalist services.

Beyond payment barriers, technology issues are a challenge to rural telemedicine. Access to affordable, simple, and reliable equipment and broadband internet is key to user satisfaction. In April 2020, the Federal Communications Commission estimated that 18 million Americans had insufficient access to broadband internet.⁴ This number points to the technological hurdles of rural telemedicine. 

Medicine, a highly relationship-based “team sport,” is another barrier to successful implementation. Whether serving as supervisor or primary attending (as noted in the evaluation by JaKa and colleagues⁵), the telehospitalist must be “on stage” for both patients and remote spoke colleagues. In our experience, telehospitalists also practice in-person daytime hospital medicine at spoke sites; this further enhances their relationship and connection with the spoke community and likely contributes to high satisfaction by hub hospitalists and spoke patients and nurses. 

These factors create a clear impetus for further evaluation of rural telemedicine programs. There is an extensive range of program structures to evaluate, from cross-coverage to a 24/7 virtual hospital. Satisfaction is also relative and must contextualize quantitative measurement to historic care models. The execution of a telehospitalist program should align with the goals and objectives of spoke hospitals, as satisfaction will reflect how well hub hospitalists are able to meet those needs. Thus, multicenter studies that examine commercial financial pressures and encompass a variety of patient populations are imperative.

A hub-and-spoke telemedicine program can be a crucial resource for rural hospitals. The foundation of this model revolves around key factors, including reliable financing, access to technology, seamless communication, and engendering satisfaction among providers, staff, and patients. Research must continue for these programs to overcome the financial and structural challenges to their success.

Common themes run through rural communities and their health needs, yet the rurality of our nation is quite diverse. Approximately 97% of the United States is rural, and yet there is no silver bullet to resolve the health disparities that exist between urban and rural America. Differences in economic condition, infrastructure, education, racial diversity, health habits, and job opportunities contribute to the health disparities seen in rural communities.

In this issue of the Journal of Hospital Medicine, Gutierrez and colleagues¹ evaluate the implementation and outcomes of a rural telehospitalist program. In a hub-and-spoke fashion, providers at a large tertiary care hospital utilized telemedicine to round on patients with an onsite advanced practice provider at a 10-bed critical access hospital. Outcomes were examined during pre- and postimplementation periods using quantitative metrics (length of stay [LOS], readmission rate, mortality, and satisfaction) and qualitative measures based on interviews with staff. LOS was reduced in the postimplementation period, with a lower but nonsignificant readmission rate and no difference in mortality. Overall satisfaction was high, although respondents noted significant communication and technology issues. This study helps broaden telemedicine research and opens the conversation on barriers in rural implementation. 

As we increasingly focus on the provision and financing of care aimed at the health of populations, the diverse issues facing rural America remain insufficiently addressed. Probst and colleagues² suggest that population-based health policies are biased toward large urban centers. Innovations to transcend this “structural urbanism” are still fraught with obstacles, as revealed during the 2020 public health emergency (PHE). Telemedicine, once thought the solution to rural health provider shortages, has not escaped structural urbanism. Prior to the PHE, Medicare did not cover many core services delivered via telehealth, including hospitalist service codes. Waivers during the PHE have temporarily opened up reimbursement pathways. Unlike most telehospitalist services, Gutierrez and colleagues did not face these payment barriers in their study. Without claims data to inform payors on the adequacy of such services, health systems remain unable to promote telemedicine as a solution to rural access and cost issues. For example, in 2018, Yu and colleagues³ described the state of telemedicine in Minnesota, again, without claims data to inform supply or demand for hospitalist services.

Beyond payment barriers, technology issues are a challenge to rural telemedicine. Access to affordable, simple, and reliable equipment and broadband internet is key to user satisfaction. In April 2020, the Federal Communications Commission estimated that 18 million Americans had insufficient access to broadband internet.⁴ This number points to the technological hurdles of rural telemedicine. 

Medicine, a highly relationship-based “team sport,” is another barrier to successful implementation. Whether serving as supervisor or primary attending (as noted in the evaluation by JaKa and colleagues⁵), the telehospitalist must be “on stage” for both patients and remote spoke colleagues. In our experience, telehospitalists also practice in-person daytime hospital medicine at spoke sites; this further enhances their relationship and connection with the spoke community and likely contributes to high satisfaction by hub hospitalists and spoke patients and nurses. 

These factors create a clear impetus for further evaluation of rural telemedicine programs. There is an extensive range of program structures to evaluate, from cross-coverage to a 24/7 virtual hospital. Satisfaction is also relative and must contextualize quantitative measurement to historic care models. The execution of a telehospitalist program should align with the goals and objectives of spoke hospitals, as satisfaction will reflect how well hub hospitalists are able to meet those needs. Thus, multicenter studies that examine commercial financial pressures and encompass a variety of patient populations are imperative.

A hub-and-spoke telemedicine program can be a crucial resource for rural hospitals. The foundation of this model revolves around key factors, including reliable financing, access to technology, seamless communication, and engendering satisfaction among providers, staff, and patients. Research must continue for these programs to overcome the financial and structural challenges to their success.

“One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient.”

—Francis Peabody, 9 years after the pandemic of 1918

Two weeks after rounding on a coronavirus disease 2019 (COVID-19) unit at the start of the surge in Detroit, Michigan, I got infected. Simultaneously, my father was also fighting COVID-19, and we were mechanically ventilated at the same time. He was admitted a week before I was and, devastatingly, died about a week after I was discharged. I have three major takeaways from my experience that now inform how I practice.

I have always appreciated what a valuable member of the team nurses are, but to experience the caring reflected in their smiling eyes, magnified by a face shield, is an indelible image—compassion with passion. They risked their lives to save my life, but I am also grateful to the maintenance person who risked their life to fix the toilet in my room in the intensive care unit, the transportation aides and radiology techs who risked their lives so I could get a computed tomography scan, environmental services personnel, and too many to mention who put on personal protective equipment to care for my father and me. Lesson #1: Repeatedly thank everyone caring for patients. Now, when I am on rounds, I try to remember to say thank you to each member each day.

As my dyspnea worsened, a big concern (besides the “I might die” thing) was communicating with family. It turns out that my short cell phone cord could only stretch to just under my pillow, and reaching that far was exhausting when on high-flow oxygen. Nursing helped me to video chat with my family as we said potential goodbyes just prior to intubation and let me use their bagged personal cell phones when I woke up. Meanwhile, my siblings took over the calls from Dad’s team, and I was amazed at how much they had learned about ventilator settings while I was sleeping and how much the clinical team knew about my family. Although Dad’s delirium never allowed meaningful conversation or eye contact with us, every day the nurses would facilitate video chatting (again, with their phones) so we could give words of love and encouragement. Lesson #2: I have redoubled my efforts to keep families in the loop and carry a phone/tablet charger with a long cord to lend/give my patients, if needed.

While I was prone, paralyzed, and sedated, I had no awareness of my medical treatments, thanks to the skill of my caregivers. It is impossible to express my gratitude to those who sent good wishes that virtually always included the phrase, “We were praying for you”; I hope my prayers got through to Dad. In their call to more fully address religion and spirituality in medicine, Collier et al¹ remind us that approximately 90% of Americans have faith, and more than half state that religion is very important to them, yet I, like many, do not routinely incorporate this aspect into my discussions with patients or the care team. Lesson #3: Begin to more actively facilitate my patients’ spirituality into the team’s caring process.

“One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient.”

—Francis Peabody, 9 years after the pandemic of 1918

Two weeks after rounding on a coronavirus disease 2019 (COVID-19) unit at the start of the surge in Detroit, Michigan, I got infected. Simultaneously, my father was also fighting COVID-19, and we were mechanically ventilated at the same time. He was admitted a week before I was and, devastatingly, died about a week after I was discharged. I have three major takeaways from my experience that now inform how I practice.

I have always appreciated what a valuable member of the team nurses are, but to experience the caring reflected in their smiling eyes, magnified by a face shield, is an indelible image—compassion with passion. They risked their lives to save my life, but I am also grateful to the maintenance person who risked their life to fix the toilet in my room in the intensive care unit, the transportation aides and radiology techs who risked their lives so I could get a computed tomography scan, environmental services personnel, and too many to mention who put on personal protective equipment to care for my father and me. Lesson #1: Repeatedly thank everyone caring for patients. Now, when I am on rounds, I try to remember to say thank you to each member each day.

As my dyspnea worsened, a big concern (besides the “I might die” thing) was communicating with family. It turns out that my short cell phone cord could only stretch to just under my pillow, and reaching that far was exhausting when on high-flow oxygen. Nursing helped me to video chat with my family as we said potential goodbyes just prior to intubation and let me use their bagged personal cell phones when I woke up. Meanwhile, my siblings took over the calls from Dad’s team, and I was amazed at how much they had learned about ventilator settings while I was sleeping and how much the clinical team knew about my family. Although Dad’s delirium never allowed meaningful conversation or eye contact with us, every day the nurses would facilitate video chatting (again, with their phones) so we could give words of love and encouragement. Lesson #2: I have redoubled my efforts to keep families in the loop and carry a phone/tablet charger with a long cord to lend/give my patients, if needed.

While I was prone, paralyzed, and sedated, I had no awareness of my medical treatments, thanks to the skill of my caregivers. It is impossible to express my gratitude to those who sent good wishes that virtually always included the phrase, “We were praying for you”; I hope my prayers got through to Dad. In their call to more fully address religion and spirituality in medicine, Collier et al¹ remind us that approximately 90% of Americans have faith, and more than half state that religion is very important to them, yet I, like many, do not routinely incorporate this aspect into my discussions with patients or the care team. Lesson #3: Begin to more actively facilitate my patients’ spirituality into the team’s caring process.

“One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is in caring for the patient.”

—Francis Peabody, 9 years after the pandemic of 1918

Two weeks after rounding on a coronavirus disease 2019 (COVID-19) unit at the start of the surge in Detroit, Michigan, I got infected. Simultaneously, my father was also fighting COVID-19, and we were mechanically ventilated at the same time. He was admitted a week before I was and, devastatingly, died about a week after I was discharged. I have three major takeaways from my experience that now inform how I practice.

I have always appreciated what a valuable member of the team nurses are, but to experience the caring reflected in their smiling eyes, magnified by a face shield, is an indelible image—compassion with passion. They risked their lives to save my life, but I am also grateful to the maintenance person who risked their life to fix the toilet in my room in the intensive care unit, the transportation aides and radiology techs who risked their lives so I could get a computed tomography scan, environmental services personnel, and too many to mention who put on personal protective equipment to care for my father and me. Lesson #1: Repeatedly thank everyone caring for patients. Now, when I am on rounds, I try to remember to say thank you to each member each day.

As my dyspnea worsened, a big concern (besides the “I might die” thing) was communicating with family. It turns out that my short cell phone cord could only stretch to just under my pillow, and reaching that far was exhausting when on high-flow oxygen. Nursing helped me to video chat with my family as we said potential goodbyes just prior to intubation and let me use their bagged personal cell phones when I woke up. Meanwhile, my siblings took over the calls from Dad’s team, and I was amazed at how much they had learned about ventilator settings while I was sleeping and how much the clinical team knew about my family. Although Dad’s delirium never allowed meaningful conversation or eye contact with us, every day the nurses would facilitate video chatting (again, with their phones) so we could give words of love and encouragement. Lesson #2: I have redoubled my efforts to keep families in the loop and carry a phone/tablet charger with a long cord to lend/give my patients, if needed.

While I was prone, paralyzed, and sedated, I had no awareness of my medical treatments, thanks to the skill of my caregivers. It is impossible to express my gratitude to those who sent good wishes that virtually always included the phrase, “We were praying for you”; I hope my prayers got through to Dad. In their call to more fully address religion and spirituality in medicine, Collier et al¹ remind us that approximately 90% of Americans have faith, and more than half state that religion is very important to them, yet I, like many, do not routinely incorporate this aspect into my discussions with patients or the care team. Lesson #3: Begin to more actively facilitate my patients’ spirituality into the team’s caring process.

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

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

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

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

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

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

Researchers have developed a proprietary computer adaptive screening tool that may help emergency departments more accurately predict suicide attempts in adolescents, according to a recent study in JAMA Psychiatry.

The computerized adaptive screen for suicidal youth (CASSY) had an area under the curve (AUC) of 0.87 in an independent validation cohort that predicted an adolescent suicide attempt within 3 months, according to Cheryl A. King, PhD, of the department of psychiatry at the University of Michigan in Ann Arbor, and colleagues. CASSY’s adaptive design, which presents different questions based on a respondent’s answers, means “an individual’s initial item responses are used to determine a provisional estimate of their standing on the measured trait,” the researchers said.

Dr. King and colleagues evaluated the CASSY algorithm in a first study that consisted of 2,845 adolescents who were mean 15.1 years old, mostly girls (63%) enrolled from 13 different emergency departments across the United States within the Pediatric Emergency Care Applied Research Network (PECARN) between June 2015 and July 2016. To develop the CASSY algorithm, the participants received a 92-item self-report survey at baseline with three “anchor” questions from the Ask Suicide-Screening Questions (ASQ) and Columbia–Suicide Severity Rating Scale (C-SSRS). Based on the answers to the baseline survey, the researchers categorized participants as being at low, medium, or high risk for a suicide attempt, and followed participants for 3 months to record suicide attempts reported by a patient or parent.

Retention of participants at 3 months was 72.9%, leaving data available for 2,075 adolescents for review. The researchers found that the AUC was 0.89 (95% confidence interval, 0.85-0.91) in the first study, with a sensitivity of 82.4% and a specificity of 80%. Participants answered a mean number of 11 items during an assessment (range, 5-21 items) administered in a median time of 1 minute, 24 seconds.

In a second study consisting of a validation cohort, 4,050 adolescents from 14 PECARN emergency departments and 1 Indian Health Service hospital were followed, with a retention of 2,754 participants (69.5%) at the end of 3 months. Of the adolescents available at the end of 3 months, 62.1% were girls with a mean age of 15.0 years. The AUC for this validation group was 0.87 (95% CI, 0.85-0.89). Of these participants, 71.5% reported no previous suicide attempts, 9% reported one prior attempt, 18.2% reported multiple attempts, and 1.2% had an unknown number of suicide attempts. During the 3-month window of the second study, 6.0% of participants had at least one suicide attempt.

The researchers said that while the CASSY instrument may be advantageous for some emergency departments, “a standard screen such as the ASQ, which consists of fewer items, may be preferred in some settings, particularly those in which the cost and technical setup of a computerized adaptive screen poses too high a barrier.”

“Important next steps will be to measure the CASSY’s test-retest reliability and develop triage recommendations and conduct implementation studies,” Dr. King and colleagues concluded.
 

Climbing adolescent suicide rate

In an interview, Igor Galynker, MD, PhD, professor in the department of psychiatry, and director of the suicide lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai, New York, said the study by Dr. King and colleagues is important during a time when the suicide rate for adolescents is substantially increasing.

According to data from the CDC’s Web-based Injury Statistics Query and Reporting System, 1,750 adolescents died of suicide in 2018, and the rate of deaths by suicide has increased by 62% since the year 2000. “The issue really needs to be addressed,” said Dr. Galynker, who was not involved with the study.

Some methods of screening suicidal ideation that open with a direct question can miss suicide attempts in individuals who do not express these suicidal ideations, he explained, and the problem can be magnified in adolescent patients. “This is particularly difficult with adolescents because they’re notoriously poor historians. They cannot describe their feelings as well. It’s even more important to have methods that work for suicide prevention for adolescents and to support those predictors which do not rely on self-report,” he said.

Dr. Galynker said that CASSY is innovative because asking whether the patient is suicidal is not the “gateway question” and does not categorize people into groups determined to be at low, medium, or high risk for a suicide attempt.

“When you categorize people – adolescents in this particular case – you remove clinical judgment from [the] clinician. You deprive [the] clinician of exercising their clinical judgment in terms of somebody is or is not likely to die by suicide. That’s a serious problem,” he said, noting it may be one reason why these screening tools have difficulty identifying patients at risk of suicide.

Regarding limitations, the 3-month follow-up window for patients in the study may be too long to be clinically meaningful.

“If somebody is in treatment, 3 months is a long time. You want to know whether somebody is going to attempt suicide before the next time you see them, which is usually a month or a week,” he said.

But a strength of the CASSY instrument, Dr. Galynker said, is its ability to capture the patient’s mental state in the moment, as opposed to relying only a patient’s electronic medical record. The study also demonstrates “it should be possible to introduce detailed suicide risk assessment in the emergency rooms, and [it] should be done,” he said.

This study was funded with support from the Health Resources and Services Administration, the Maternal and Child Health Bureau, and the Emergency Medical Services for Children Network Development Demonstration Program, and a grant by the National Institute of Mental Health for the Emergency Department Screen for Teens at Risk for Suicide. Twelve authors reported personal and institutional relationships in the form of fees, grants, consultancies, royalties, copyrighted work, founding of technologies, and scientific council memberships for a variety of agencies, societies, foundations, and other organizations inside and outside of the study. Dr. Galynker reported his work unrelated to the study is supported by the National Institute of Mental Health and the American Foundation for Suicide Prevention. But he has no proprietary interests.
 

[email protected]

Researchers have developed a proprietary computer adaptive screening tool that may help emergency departments more accurately predict suicide attempts in adolescents, according to a recent study in JAMA Psychiatry.

The computerized adaptive screen for suicidal youth (CASSY) had an area under the curve (AUC) of 0.87 in an independent validation cohort that predicted an adolescent suicide attempt within 3 months, according to Cheryl A. King, PhD, of the department of psychiatry at the University of Michigan in Ann Arbor, and colleagues. CASSY’s adaptive design, which presents different questions based on a respondent’s answers, means “an individual’s initial item responses are used to determine a provisional estimate of their standing on the measured trait,” the researchers said.

Dr. King and colleagues evaluated the CASSY algorithm in a first study that consisted of 2,845 adolescents who were mean 15.1 years old, mostly girls (63%) enrolled from 13 different emergency departments across the United States within the Pediatric Emergency Care Applied Research Network (PECARN) between June 2015 and July 2016. To develop the CASSY algorithm, the participants received a 92-item self-report survey at baseline with three “anchor” questions from the Ask Suicide-Screening Questions (ASQ) and Columbia–Suicide Severity Rating Scale (C-SSRS). Based on the answers to the baseline survey, the researchers categorized participants as being at low, medium, or high risk for a suicide attempt, and followed participants for 3 months to record suicide attempts reported by a patient or parent.

Retention of participants at 3 months was 72.9%, leaving data available for 2,075 adolescents for review. The researchers found that the AUC was 0.89 (95% confidence interval, 0.85-0.91) in the first study, with a sensitivity of 82.4% and a specificity of 80%. Participants answered a mean number of 11 items during an assessment (range, 5-21 items) administered in a median time of 1 minute, 24 seconds.

In a second study consisting of a validation cohort, 4,050 adolescents from 14 PECARN emergency departments and 1 Indian Health Service hospital were followed, with a retention of 2,754 participants (69.5%) at the end of 3 months. Of the adolescents available at the end of 3 months, 62.1% were girls with a mean age of 15.0 years. The AUC for this validation group was 0.87 (95% CI, 0.85-0.89). Of these participants, 71.5% reported no previous suicide attempts, 9% reported one prior attempt, 18.2% reported multiple attempts, and 1.2% had an unknown number of suicide attempts. During the 3-month window of the second study, 6.0% of participants had at least one suicide attempt.

The researchers said that while the CASSY instrument may be advantageous for some emergency departments, “a standard screen such as the ASQ, which consists of fewer items, may be preferred in some settings, particularly those in which the cost and technical setup of a computerized adaptive screen poses too high a barrier.”

“Important next steps will be to measure the CASSY’s test-retest reliability and develop triage recommendations and conduct implementation studies,” Dr. King and colleagues concluded.
 

Climbing adolescent suicide rate

In an interview, Igor Galynker, MD, PhD, professor in the department of psychiatry, and director of the suicide lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai, New York, said the study by Dr. King and colleagues is important during a time when the suicide rate for adolescents is substantially increasing.

According to data from the CDC’s Web-based Injury Statistics Query and Reporting System, 1,750 adolescents died of suicide in 2018, and the rate of deaths by suicide has increased by 62% since the year 2000. “The issue really needs to be addressed,” said Dr. Galynker, who was not involved with the study.

Some methods of screening suicidal ideation that open with a direct question can miss suicide attempts in individuals who do not express these suicidal ideations, he explained, and the problem can be magnified in adolescent patients. “This is particularly difficult with adolescents because they’re notoriously poor historians. They cannot describe their feelings as well. It’s even more important to have methods that work for suicide prevention for adolescents and to support those predictors which do not rely on self-report,” he said.

Dr. Galynker said that CASSY is innovative because asking whether the patient is suicidal is not the “gateway question” and does not categorize people into groups determined to be at low, medium, or high risk for a suicide attempt.

“When you categorize people – adolescents in this particular case – you remove clinical judgment from [the] clinician. You deprive [the] clinician of exercising their clinical judgment in terms of somebody is or is not likely to die by suicide. That’s a serious problem,” he said, noting it may be one reason why these screening tools have difficulty identifying patients at risk of suicide.

Regarding limitations, the 3-month follow-up window for patients in the study may be too long to be clinically meaningful.

“If somebody is in treatment, 3 months is a long time. You want to know whether somebody is going to attempt suicide before the next time you see them, which is usually a month or a week,” he said.

But a strength of the CASSY instrument, Dr. Galynker said, is its ability to capture the patient’s mental state in the moment, as opposed to relying only a patient’s electronic medical record. The study also demonstrates “it should be possible to introduce detailed suicide risk assessment in the emergency rooms, and [it] should be done,” he said.

This study was funded with support from the Health Resources and Services Administration, the Maternal and Child Health Bureau, and the Emergency Medical Services for Children Network Development Demonstration Program, and a grant by the National Institute of Mental Health for the Emergency Department Screen for Teens at Risk for Suicide. Twelve authors reported personal and institutional relationships in the form of fees, grants, consultancies, royalties, copyrighted work, founding of technologies, and scientific council memberships for a variety of agencies, societies, foundations, and other organizations inside and outside of the study. Dr. Galynker reported his work unrelated to the study is supported by the National Institute of Mental Health and the American Foundation for Suicide Prevention. But he has no proprietary interests.
 

[email protected]

Researchers have developed a proprietary computer adaptive screening tool that may help emergency departments more accurately predict suicide attempts in adolescents, according to a recent study in JAMA Psychiatry.

The computerized adaptive screen for suicidal youth (CASSY) had an area under the curve (AUC) of 0.87 in an independent validation cohort that predicted an adolescent suicide attempt within 3 months, according to Cheryl A. King, PhD, of the department of psychiatry at the University of Michigan in Ann Arbor, and colleagues. CASSY’s adaptive design, which presents different questions based on a respondent’s answers, means “an individual’s initial item responses are used to determine a provisional estimate of their standing on the measured trait,” the researchers said.

Dr. King and colleagues evaluated the CASSY algorithm in a first study that consisted of 2,845 adolescents who were mean 15.1 years old, mostly girls (63%) enrolled from 13 different emergency departments across the United States within the Pediatric Emergency Care Applied Research Network (PECARN) between June 2015 and July 2016. To develop the CASSY algorithm, the participants received a 92-item self-report survey at baseline with three “anchor” questions from the Ask Suicide-Screening Questions (ASQ) and Columbia–Suicide Severity Rating Scale (C-SSRS). Based on the answers to the baseline survey, the researchers categorized participants as being at low, medium, or high risk for a suicide attempt, and followed participants for 3 months to record suicide attempts reported by a patient or parent.

Retention of participants at 3 months was 72.9%, leaving data available for 2,075 adolescents for review. The researchers found that the AUC was 0.89 (95% confidence interval, 0.85-0.91) in the first study, with a sensitivity of 82.4% and a specificity of 80%. Participants answered a mean number of 11 items during an assessment (range, 5-21 items) administered in a median time of 1 minute, 24 seconds.

In a second study consisting of a validation cohort, 4,050 adolescents from 14 PECARN emergency departments and 1 Indian Health Service hospital were followed, with a retention of 2,754 participants (69.5%) at the end of 3 months. Of the adolescents available at the end of 3 months, 62.1% were girls with a mean age of 15.0 years. The AUC for this validation group was 0.87 (95% CI, 0.85-0.89). Of these participants, 71.5% reported no previous suicide attempts, 9% reported one prior attempt, 18.2% reported multiple attempts, and 1.2% had an unknown number of suicide attempts. During the 3-month window of the second study, 6.0% of participants had at least one suicide attempt.

The researchers said that while the CASSY instrument may be advantageous for some emergency departments, “a standard screen such as the ASQ, which consists of fewer items, may be preferred in some settings, particularly those in which the cost and technical setup of a computerized adaptive screen poses too high a barrier.”

“Important next steps will be to measure the CASSY’s test-retest reliability and develop triage recommendations and conduct implementation studies,” Dr. King and colleagues concluded.
 

Climbing adolescent suicide rate

In an interview, Igor Galynker, MD, PhD, professor in the department of psychiatry, and director of the suicide lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai, New York, said the study by Dr. King and colleagues is important during a time when the suicide rate for adolescents is substantially increasing.

According to data from the CDC’s Web-based Injury Statistics Query and Reporting System, 1,750 adolescents died of suicide in 2018, and the rate of deaths by suicide has increased by 62% since the year 2000. “The issue really needs to be addressed,” said Dr. Galynker, who was not involved with the study.

Some methods of screening suicidal ideation that open with a direct question can miss suicide attempts in individuals who do not express these suicidal ideations, he explained, and the problem can be magnified in adolescent patients. “This is particularly difficult with adolescents because they’re notoriously poor historians. They cannot describe their feelings as well. It’s even more important to have methods that work for suicide prevention for adolescents and to support those predictors which do not rely on self-report,” he said.

Dr. Galynker said that CASSY is innovative because asking whether the patient is suicidal is not the “gateway question” and does not categorize people into groups determined to be at low, medium, or high risk for a suicide attempt.

“When you categorize people – adolescents in this particular case – you remove clinical judgment from [the] clinician. You deprive [the] clinician of exercising their clinical judgment in terms of somebody is or is not likely to die by suicide. That’s a serious problem,” he said, noting it may be one reason why these screening tools have difficulty identifying patients at risk of suicide.

Regarding limitations, the 3-month follow-up window for patients in the study may be too long to be clinically meaningful.

“If somebody is in treatment, 3 months is a long time. You want to know whether somebody is going to attempt suicide before the next time you see them, which is usually a month or a week,” he said.

But a strength of the CASSY instrument, Dr. Galynker said, is its ability to capture the patient’s mental state in the moment, as opposed to relying only a patient’s electronic medical record. The study also demonstrates “it should be possible to introduce detailed suicide risk assessment in the emergency rooms, and [it] should be done,” he said.

This study was funded with support from the Health Resources and Services Administration, the Maternal and Child Health Bureau, and the Emergency Medical Services for Children Network Development Demonstration Program, and a grant by the National Institute of Mental Health for the Emergency Department Screen for Teens at Risk for Suicide. Twelve authors reported personal and institutional relationships in the form of fees, grants, consultancies, royalties, copyrighted work, founding of technologies, and scientific council memberships for a variety of agencies, societies, foundations, and other organizations inside and outside of the study. Dr. Galynker reported his work unrelated to the study is supported by the National Institute of Mental Health and the American Foundation for Suicide Prevention. But he has no proprietary interests.
 

[email protected]

In a time when this country is struggling to find topics on which we can achieve broad consensus, the question of whether in-class learning is important stands as an outlier. Parents, teachers, students, and pediatricians all agree that having children learn in a social, face-to-face environment is critical to their education and mental health. Because school has become a de facto daycare source for many families, employers have joined in the chorus supporting a return to in-class education.

Of course, beyond that basic point of agreement the myriad of questions relating to when and how that return to the educational norm can be achieved we divide into groups with almost as many answers as there are questions. Part of the problem stems from the national leadership vacuum that fed the confusion. In this void the topic of school reopening has become politicized.

On Jan. 5, 2021, the American Academy of Pediatrics released an updated interim COVID-19 Guidance for Safe Schools at services.aap.org. It is a thorough and well thought out document that should function as a roadmap for communities and pediatricians who serve as official and unofficial advisers to their local school departments. At the very outset it reminds us that “school transmission mirrors but does not drive community transmission.”

Unfortunately, timing is everything and while the document’s salient points received some media attention it was mostly buried by the tsunami of press coverage in the wake of the storming of the Capitol the next day and the postinauguration reshuffling of the federal government. Even if it had been released on one of those seldom seen quiet news days, I fear the document’s message encouraging the return to in-class learning would have still not received the attention it deserved.

The lack of a high-visibility celebrity spokesperson and a system of short-tenure presidencies puts the AAP at a disadvantage when it comes to getting its message across to a national audience. The advocacy role filters down to those of us in our own communities who must convince school boards that not only is in-class learning critical but there are safe ways to do it.

In some communities the timing of return to in-class learning may pit pediatricians against teachers. Usually, these two groups share an enthusiastic advocacy for children. However, facing what has up to this point been a poorly defined health risk, teachers are understandably resistant to return to the classroom although they acknowledge its importance.

Armed with the AAP’s guidance document, pediatricians should encourage school boards and state and local health departments to look closely at the epidemiologic evidence and consider creative ways to prioritize teachers for what currently are limited and erratic vaccine supplies. Strategies might include offering vaccines to teachers based strictly on their age and/or health status. However, teachers and in-class education are so critical to the educational process and the national economy that an open offer to all teachers makes more sense.

While some states have already prioritized teachers for vaccines, the AAP must continue to speak loudly that in-class education is critical and urge all states to do what is necessary to make teachers feel safe to return to the classroom.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a time when this country is struggling to find topics on which we can achieve broad consensus, the question of whether in-class learning is important stands as an outlier. Parents, teachers, students, and pediatricians all agree that having children learn in a social, face-to-face environment is critical to their education and mental health. Because school has become a de facto daycare source for many families, employers have joined in the chorus supporting a return to in-class education.

Of course, beyond that basic point of agreement the myriad of questions relating to when and how that return to the educational norm can be achieved we divide into groups with almost as many answers as there are questions. Part of the problem stems from the national leadership vacuum that fed the confusion. In this void the topic of school reopening has become politicized.

On Jan. 5, 2021, the American Academy of Pediatrics released an updated interim COVID-19 Guidance for Safe Schools at services.aap.org. It is a thorough and well thought out document that should function as a roadmap for communities and pediatricians who serve as official and unofficial advisers to their local school departments. At the very outset it reminds us that “school transmission mirrors but does not drive community transmission.”

Unfortunately, timing is everything and while the document’s salient points received some media attention it was mostly buried by the tsunami of press coverage in the wake of the storming of the Capitol the next day and the postinauguration reshuffling of the federal government. Even if it had been released on one of those seldom seen quiet news days, I fear the document’s message encouraging the return to in-class learning would have still not received the attention it deserved.

The lack of a high-visibility celebrity spokesperson and a system of short-tenure presidencies puts the AAP at a disadvantage when it comes to getting its message across to a national audience. The advocacy role filters down to those of us in our own communities who must convince school boards that not only is in-class learning critical but there are safe ways to do it.

In some communities the timing of return to in-class learning may pit pediatricians against teachers. Usually, these two groups share an enthusiastic advocacy for children. However, facing what has up to this point been a poorly defined health risk, teachers are understandably resistant to return to the classroom although they acknowledge its importance.

Armed with the AAP’s guidance document, pediatricians should encourage school boards and state and local health departments to look closely at the epidemiologic evidence and consider creative ways to prioritize teachers for what currently are limited and erratic vaccine supplies. Strategies might include offering vaccines to teachers based strictly on their age and/or health status. However, teachers and in-class education are so critical to the educational process and the national economy that an open offer to all teachers makes more sense.

While some states have already prioritized teachers for vaccines, the AAP must continue to speak loudly that in-class education is critical and urge all states to do what is necessary to make teachers feel safe to return to the classroom.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a time when this country is struggling to find topics on which we can achieve broad consensus, the question of whether in-class learning is important stands as an outlier. Parents, teachers, students, and pediatricians all agree that having children learn in a social, face-to-face environment is critical to their education and mental health. Because school has become a de facto daycare source for many families, employers have joined in the chorus supporting a return to in-class education.

Of course, beyond that basic point of agreement the myriad of questions relating to when and how that return to the educational norm can be achieved we divide into groups with almost as many answers as there are questions. Part of the problem stems from the national leadership vacuum that fed the confusion. In this void the topic of school reopening has become politicized.

On Jan. 5, 2021, the American Academy of Pediatrics released an updated interim COVID-19 Guidance for Safe Schools at services.aap.org. It is a thorough and well thought out document that should function as a roadmap for communities and pediatricians who serve as official and unofficial advisers to their local school departments. At the very outset it reminds us that “school transmission mirrors but does not drive community transmission.”

Unfortunately, timing is everything and while the document’s salient points received some media attention it was mostly buried by the tsunami of press coverage in the wake of the storming of the Capitol the next day and the postinauguration reshuffling of the federal government. Even if it had been released on one of those seldom seen quiet news days, I fear the document’s message encouraging the return to in-class learning would have still not received the attention it deserved.

The lack of a high-visibility celebrity spokesperson and a system of short-tenure presidencies puts the AAP at a disadvantage when it comes to getting its message across to a national audience. The advocacy role filters down to those of us in our own communities who must convince school boards that not only is in-class learning critical but there are safe ways to do it.

In some communities the timing of return to in-class learning may pit pediatricians against teachers. Usually, these two groups share an enthusiastic advocacy for children. However, facing what has up to this point been a poorly defined health risk, teachers are understandably resistant to return to the classroom although they acknowledge its importance.

Armed with the AAP’s guidance document, pediatricians should encourage school boards and state and local health departments to look closely at the epidemiologic evidence and consider creative ways to prioritize teachers for what currently are limited and erratic vaccine supplies. Strategies might include offering vaccines to teachers based strictly on their age and/or health status. However, teachers and in-class education are so critical to the educational process and the national economy that an open offer to all teachers makes more sense.

While some states have already prioritized teachers for vaccines, the AAP must continue to speak loudly that in-class education is critical and urge all states to do what is necessary to make teachers feel safe to return to the classroom.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

Despite their similar functions, each current and emerging therapy for treating hemophilia has a unique safety profile, and each needs to be weighed apart from agents both within and outside its pharmacologic class, a hemophilia specialist said.

“My view is that each new molecule coming to the hemophilia space, including variant factor molecules, needs to be scrutinized separately, without class assumptions or extrapolations, and it’s clear that thrombosis risk has become a priority safety consideration,” said Dan Hart, MBChB, MRCP, FRCPath, PhD, from Barts and the London School of Medicine and Dentistry.

He reviewed the comparative safety of standard and novel therapies for hemophilia at the annual congress of the European Association for Haemophilia and Allied Disorders.
 

Factor inhibitors

Inhibitors occur in both hemophilia A and hemophilia B, and are primarily seen in patients with childhood exposure to factor concentrates. Inhibitors, which include anti–factor VIII and factor IX alloantibodies, are more common among patients with severe hemophilia and those with more disruptive factor VIII and factor IX mutations.

“There can be transient vs. persistent inhibitors, and arguably the more you look, the more you find, but clinically we never miss high-titer inhibitors that have a big impact on individuals and the subsequent decisions about management,” he said.
 

Hamster vs. human

It’s currently unclear whether there is an immunologic advantage for previously untreated patients to be started on factor VIII concentrates derived from recombinant human cells lines, or from products derived from Chinese hamster ovary (CHO) or baby hamster kidney (BHK) cell lines, Dr. Hart said.

“We need to ensure that we’re not selective about comparator choice for new products in the absence of head-to-head studies,” he said.
 

Route of administration matters

Inhibitors appear to be a more common occurrence among patients who received factor concentrates subcutaneously, compared with intravenously, Dr. Hart noted, pointing to a 2011 study indicating a background annual risk of 5 cases of inhibitor development per 1,000 treatment years in previously treated patients who received intravenous therapy (Blood. 2011 Jun 9;117[23]:6367-70).

In contrast, in a phase 1 trial of subcutaneous turoctocog alfa pegol, 5 out of 26 patients had detectable N8-GP–binding antibodies after 42-91 exposure days. Of these patients, one developed an inhibitor to factor VIII, and anti–N8-GP antibody appearance was associated with a decline in factor VIII plasma activity in four of the five patients. In addition, five patients reported a total of nine bleeding episodes requiring treatment during prophylaxis. As a result of this trial, further clinical development of the subcutaneous version was suspended. (J Thromb Haemost. 2020 Feb;18[2]:341-51).

Other subcutaneously administered factors are currently in development, Dr. Hart noted.
 

Nonfactor inhibitors?

“The nonfactor agents do have the risk of generating antibodies: Monoclonal antibodies outside the hemophilia setting provoke antidrug antibodies,” he said.

Although there is no consensus regarding which assay can best monitor antidrug antibodies (ADA), enzyme-linked immunosorbent assay (ELISA) can detect neutralizing antibodies and other antibodies.

In the hemophilia setting, surrogate markers for loss of drug efficacy include longer activated partial thromboplastin time (ATTP) or a drop in serum drug levels. Worsening bleeding phenotype can also be a marker for loss of efficacy, albeit an imperfect one.

Emicizumab (Hemlibara), the first nonfactor monoclonal agent to make it to market, has the largest dataset available, and evidence suggests a rate of neutralizing antibodies with this agent of less than 1% in the HAVEN clinical trial series, but 5.2% in the single-arm STASEY trial.

“We shouldn’t assume that other biophenotypics will have a similar ADA rate, and this needs to be evaluated for each molecule, as it will need to be for other monoclonals” such as anti–tissue factor pathway (TFPI) antibodies, Dr. Hart emphasized.
 

Pegylation

Pegylated compounds include polyethylene glycol, an inert polymer, covalently bound to the therapeutic protein to extend its half-life, and theoretically, reduce immunogenicity.

Many patients may already have exposure to pegylated products in the form of peginterferon to treat hepatitis C, consumer products such as toothpaste, cough medicine, and cosmetics, and, more recently, in vaccines against COVID-19.

Safety considerations with pegylated agents in hemophilia include concerns about accumulation of polyethylene glycol (PEG), although “some of the preclinical models looking at excretion of PEG are difficult to interpret in my view, and people debate about whether studies are long enough, but it’s undoubtedly the case that toxicology dosing is order of magnitude higher than the routine dosing in hemophilia,” he said.

After more than 5 years of experience with pegylated products there is no clinical evidence of concern, although “it’s not clear, actually, what we’re looking for, whether it’s a clinical parameter, or imaging or histological parameter.”

Patients may also not have lifelong exposure to pegylated products, as it is unlikely that they will stay on the same product for decades, Dr. Hart said.
 

Thrombosis

As of June 30, 2020, more than 7,200 persons with hemophilia have received emicizumab, and there have been 23 reported thrombotic events, 19 of which occurred in the postmarketing period. Of the reported cases, six patients had a myocardial infarction, and all of these patients had at least one cardiovascular risk factor.

The antithrombin agent fitusiran was associated with one fatal thrombotic event in a phase 2, open-label extension trial, leading to a pause and resumption with mitigation protocols, but that trial has since been paused again because of additional, nonfatal thrombotic events.

Nonfatal thrombotic events have also occurred in clinical trials for the investigational anti-TFPI monoclonal antibodies BAY 1093884 and concizumab, but none have thus far been reported in phase 3 trial of marstacimab.

“We need renewed efforts for prospective reporting and independent review of all adverse events of all agents, old and new: This will need some guidance nationally and internationally, and I think the relevant trial [serious adverse events] need to be reported in peer review literature, and clinicaltrials.gov updated in a timely manner, regardless of whether that strategy was successful or unsuccessful,” Dr. Hart said.
 

Risk with longer-acting agents?

In the question and answer following his presentation, Christoph Königs, MD, PhD, from University Hospital Frankfurt, asked whether there was potential for increased thrombosis risk with second-generation extended half-life (EHL) molecules in clinical trials.

“As we edge towards normalization of hemostasis, clearly the other non–hemophilia dependent issues of thrombosis risk come into play,” Dr. Hart acknowledged. “I think it will be an inevitability that there will be events, and we need to understand what the denominators are – hence my pitch for there being a renewed effort to try and collate sufficient data that we can really define events happening with people treated with standard half-life [products] through into the novel agents,” he said.

Dr. Hart disclosed grant/research support and speaker bureau activities for Bayer, Octapharma, Takeda, and others. Dr. Königs has reported no relevant disclosures.

Despite their similar functions, each current and emerging therapy for treating hemophilia has a unique safety profile, and each needs to be weighed apart from agents both within and outside its pharmacologic class, a hemophilia specialist said.

“My view is that each new molecule coming to the hemophilia space, including variant factor molecules, needs to be scrutinized separately, without class assumptions or extrapolations, and it’s clear that thrombosis risk has become a priority safety consideration,” said Dan Hart, MBChB, MRCP, FRCPath, PhD, from Barts and the London School of Medicine and Dentistry.

He reviewed the comparative safety of standard and novel therapies for hemophilia at the annual congress of the European Association for Haemophilia and Allied Disorders.
 

Factor inhibitors

Inhibitors occur in both hemophilia A and hemophilia B, and are primarily seen in patients with childhood exposure to factor concentrates. Inhibitors, which include anti–factor VIII and factor IX alloantibodies, are more common among patients with severe hemophilia and those with more disruptive factor VIII and factor IX mutations.

“There can be transient vs. persistent inhibitors, and arguably the more you look, the more you find, but clinically we never miss high-titer inhibitors that have a big impact on individuals and the subsequent decisions about management,” he said.
 

Hamster vs. human

It’s currently unclear whether there is an immunologic advantage for previously untreated patients to be started on factor VIII concentrates derived from recombinant human cells lines, or from products derived from Chinese hamster ovary (CHO) or baby hamster kidney (BHK) cell lines, Dr. Hart said.

“We need to ensure that we’re not selective about comparator choice for new products in the absence of head-to-head studies,” he said.
 

Route of administration matters

Inhibitors appear to be a more common occurrence among patients who received factor concentrates subcutaneously, compared with intravenously, Dr. Hart noted, pointing to a 2011 study indicating a background annual risk of 5 cases of inhibitor development per 1,000 treatment years in previously treated patients who received intravenous therapy (Blood. 2011 Jun 9;117[23]:6367-70).

In contrast, in a phase 1 trial of subcutaneous turoctocog alfa pegol, 5 out of 26 patients had detectable N8-GP–binding antibodies after 42-91 exposure days. Of these patients, one developed an inhibitor to factor VIII, and anti–N8-GP antibody appearance was associated with a decline in factor VIII plasma activity in four of the five patients. In addition, five patients reported a total of nine bleeding episodes requiring treatment during prophylaxis. As a result of this trial, further clinical development of the subcutaneous version was suspended. (J Thromb Haemost. 2020 Feb;18[2]:341-51).

Other subcutaneously administered factors are currently in development, Dr. Hart noted.
 

Nonfactor inhibitors?

“The nonfactor agents do have the risk of generating antibodies: Monoclonal antibodies outside the hemophilia setting provoke antidrug antibodies,” he said.

Although there is no consensus regarding which assay can best monitor antidrug antibodies (ADA), enzyme-linked immunosorbent assay (ELISA) can detect neutralizing antibodies and other antibodies.

In the hemophilia setting, surrogate markers for loss of drug efficacy include longer activated partial thromboplastin time (ATTP) or a drop in serum drug levels. Worsening bleeding phenotype can also be a marker for loss of efficacy, albeit an imperfect one.

Emicizumab (Hemlibara), the first nonfactor monoclonal agent to make it to market, has the largest dataset available, and evidence suggests a rate of neutralizing antibodies with this agent of less than 1% in the HAVEN clinical trial series, but 5.2% in the single-arm STASEY trial.

“We shouldn’t assume that other biophenotypics will have a similar ADA rate, and this needs to be evaluated for each molecule, as it will need to be for other monoclonals” such as anti–tissue factor pathway (TFPI) antibodies, Dr. Hart emphasized.
 

Pegylation

Pegylated compounds include polyethylene glycol, an inert polymer, covalently bound to the therapeutic protein to extend its half-life, and theoretically, reduce immunogenicity.

Many patients may already have exposure to pegylated products in the form of peginterferon to treat hepatitis C, consumer products such as toothpaste, cough medicine, and cosmetics, and, more recently, in vaccines against COVID-19.

Safety considerations with pegylated agents in hemophilia include concerns about accumulation of polyethylene glycol (PEG), although “some of the preclinical models looking at excretion of PEG are difficult to interpret in my view, and people debate about whether studies are long enough, but it’s undoubtedly the case that toxicology dosing is order of magnitude higher than the routine dosing in hemophilia,” he said.

After more than 5 years of experience with pegylated products there is no clinical evidence of concern, although “it’s not clear, actually, what we’re looking for, whether it’s a clinical parameter, or imaging or histological parameter.”

Patients may also not have lifelong exposure to pegylated products, as it is unlikely that they will stay on the same product for decades, Dr. Hart said.
 

Thrombosis

As of June 30, 2020, more than 7,200 persons with hemophilia have received emicizumab, and there have been 23 reported thrombotic events, 19 of which occurred in the postmarketing period. Of the reported cases, six patients had a myocardial infarction, and all of these patients had at least one cardiovascular risk factor.

The antithrombin agent fitusiran was associated with one fatal thrombotic event in a phase 2, open-label extension trial, leading to a pause and resumption with mitigation protocols, but that trial has since been paused again because of additional, nonfatal thrombotic events.

Nonfatal thrombotic events have also occurred in clinical trials for the investigational anti-TFPI monoclonal antibodies BAY 1093884 and concizumab, but none have thus far been reported in phase 3 trial of marstacimab.

“We need renewed efforts for prospective reporting and independent review of all adverse events of all agents, old and new: This will need some guidance nationally and internationally, and I think the relevant trial [serious adverse events] need to be reported in peer review literature, and clinicaltrials.gov updated in a timely manner, regardless of whether that strategy was successful or unsuccessful,” Dr. Hart said.
 

Risk with longer-acting agents?

In the question and answer following his presentation, Christoph Königs, MD, PhD, from University Hospital Frankfurt, asked whether there was potential for increased thrombosis risk with second-generation extended half-life (EHL) molecules in clinical trials.

“As we edge towards normalization of hemostasis, clearly the other non–hemophilia dependent issues of thrombosis risk come into play,” Dr. Hart acknowledged. “I think it will be an inevitability that there will be events, and we need to understand what the denominators are – hence my pitch for there being a renewed effort to try and collate sufficient data that we can really define events happening with people treated with standard half-life [products] through into the novel agents,” he said.

Dr. Hart disclosed grant/research support and speaker bureau activities for Bayer, Octapharma, Takeda, and others. Dr. Königs has reported no relevant disclosures.

Despite their similar functions, each current and emerging therapy for treating hemophilia has a unique safety profile, and each needs to be weighed apart from agents both within and outside its pharmacologic class, a hemophilia specialist said.

“My view is that each new molecule coming to the hemophilia space, including variant factor molecules, needs to be scrutinized separately, without class assumptions or extrapolations, and it’s clear that thrombosis risk has become a priority safety consideration,” said Dan Hart, MBChB, MRCP, FRCPath, PhD, from Barts and the London School of Medicine and Dentistry.

He reviewed the comparative safety of standard and novel therapies for hemophilia at the annual congress of the European Association for Haemophilia and Allied Disorders.
 

Factor inhibitors

Inhibitors occur in both hemophilia A and hemophilia B, and are primarily seen in patients with childhood exposure to factor concentrates. Inhibitors, which include anti–factor VIII and factor IX alloantibodies, are more common among patients with severe hemophilia and those with more disruptive factor VIII and factor IX mutations.

“There can be transient vs. persistent inhibitors, and arguably the more you look, the more you find, but clinically we never miss high-titer inhibitors that have a big impact on individuals and the subsequent decisions about management,” he said.
 

Hamster vs. human

It’s currently unclear whether there is an immunologic advantage for previously untreated patients to be started on factor VIII concentrates derived from recombinant human cells lines, or from products derived from Chinese hamster ovary (CHO) or baby hamster kidney (BHK) cell lines, Dr. Hart said.

“We need to ensure that we’re not selective about comparator choice for new products in the absence of head-to-head studies,” he said.
 

Route of administration matters

Inhibitors appear to be a more common occurrence among patients who received factor concentrates subcutaneously, compared with intravenously, Dr. Hart noted, pointing to a 2011 study indicating a background annual risk of 5 cases of inhibitor development per 1,000 treatment years in previously treated patients who received intravenous therapy (Blood. 2011 Jun 9;117[23]:6367-70).

In contrast, in a phase 1 trial of subcutaneous turoctocog alfa pegol, 5 out of 26 patients had detectable N8-GP–binding antibodies after 42-91 exposure days. Of these patients, one developed an inhibitor to factor VIII, and anti–N8-GP antibody appearance was associated with a decline in factor VIII plasma activity in four of the five patients. In addition, five patients reported a total of nine bleeding episodes requiring treatment during prophylaxis. As a result of this trial, further clinical development of the subcutaneous version was suspended. (J Thromb Haemost. 2020 Feb;18[2]:341-51).

Other subcutaneously administered factors are currently in development, Dr. Hart noted.
 

Nonfactor inhibitors?

“The nonfactor agents do have the risk of generating antibodies: Monoclonal antibodies outside the hemophilia setting provoke antidrug antibodies,” he said.

Although there is no consensus regarding which assay can best monitor antidrug antibodies (ADA), enzyme-linked immunosorbent assay (ELISA) can detect neutralizing antibodies and other antibodies.

In the hemophilia setting, surrogate markers for loss of drug efficacy include longer activated partial thromboplastin time (ATTP) or a drop in serum drug levels. Worsening bleeding phenotype can also be a marker for loss of efficacy, albeit an imperfect one.

Emicizumab (Hemlibara), the first nonfactor monoclonal agent to make it to market, has the largest dataset available, and evidence suggests a rate of neutralizing antibodies with this agent of less than 1% in the HAVEN clinical trial series, but 5.2% in the single-arm STASEY trial.

“We shouldn’t assume that other biophenotypics will have a similar ADA rate, and this needs to be evaluated for each molecule, as it will need to be for other monoclonals” such as anti–tissue factor pathway (TFPI) antibodies, Dr. Hart emphasized.
 

Pegylation

Pegylated compounds include polyethylene glycol, an inert polymer, covalently bound to the therapeutic protein to extend its half-life, and theoretically, reduce immunogenicity.

Many patients may already have exposure to pegylated products in the form of peginterferon to treat hepatitis C, consumer products such as toothpaste, cough medicine, and cosmetics, and, more recently, in vaccines against COVID-19.

Safety considerations with pegylated agents in hemophilia include concerns about accumulation of polyethylene glycol (PEG), although “some of the preclinical models looking at excretion of PEG are difficult to interpret in my view, and people debate about whether studies are long enough, but it’s undoubtedly the case that toxicology dosing is order of magnitude higher than the routine dosing in hemophilia,” he said.

After more than 5 years of experience with pegylated products there is no clinical evidence of concern, although “it’s not clear, actually, what we’re looking for, whether it’s a clinical parameter, or imaging or histological parameter.”

Patients may also not have lifelong exposure to pegylated products, as it is unlikely that they will stay on the same product for decades, Dr. Hart said.
 

Thrombosis

As of June 30, 2020, more than 7,200 persons with hemophilia have received emicizumab, and there have been 23 reported thrombotic events, 19 of which occurred in the postmarketing period. Of the reported cases, six patients had a myocardial infarction, and all of these patients had at least one cardiovascular risk factor.

The antithrombin agent fitusiran was associated with one fatal thrombotic event in a phase 2, open-label extension trial, leading to a pause and resumption with mitigation protocols, but that trial has since been paused again because of additional, nonfatal thrombotic events.

Nonfatal thrombotic events have also occurred in clinical trials for the investigational anti-TFPI monoclonal antibodies BAY 1093884 and concizumab, but none have thus far been reported in phase 3 trial of marstacimab.

“We need renewed efforts for prospective reporting and independent review of all adverse events of all agents, old and new: This will need some guidance nationally and internationally, and I think the relevant trial [serious adverse events] need to be reported in peer review literature, and clinicaltrials.gov updated in a timely manner, regardless of whether that strategy was successful or unsuccessful,” Dr. Hart said.
 

Risk with longer-acting agents?

In the question and answer following his presentation, Christoph Königs, MD, PhD, from University Hospital Frankfurt, asked whether there was potential for increased thrombosis risk with second-generation extended half-life (EHL) molecules in clinical trials.

“As we edge towards normalization of hemostasis, clearly the other non–hemophilia dependent issues of thrombosis risk come into play,” Dr. Hart acknowledged. “I think it will be an inevitability that there will be events, and we need to understand what the denominators are – hence my pitch for there being a renewed effort to try and collate sufficient data that we can really define events happening with people treated with standard half-life [products] through into the novel agents,” he said.

Dr. Hart disclosed grant/research support and speaker bureau activities for Bayer, Octapharma, Takeda, and others. Dr. Königs has reported no relevant disclosures.

People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.

Choreograph/iStock/Getty Images

“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”

The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.

“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.

So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
 

Some risks are real

The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.

Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.

It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.

The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.

Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.

Courtesy University of Alabama at Birmingham

How well does it work?

One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.

The guidelines specify that some drug regimens be modified when patients are vaccinated.

For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”

The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.

It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.

For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.

For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.

None of this advice should supersede clinical judgment, Dr. Curtis said.

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

People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.

Choreograph/iStock/Getty Images

“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”

The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.

“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.

So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
 

Some risks are real

The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.

Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.

It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.

The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.

Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.

Courtesy University of Alabama at Birmingham

How well does it work?

One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.

The guidelines specify that some drug regimens be modified when patients are vaccinated.

For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”

The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.

It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.

For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.

For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.

None of this advice should supersede clinical judgment, Dr. Curtis said.

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

People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.

Choreograph/iStock/Getty Images

“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”

The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.

“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.

So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
 

Some risks are real

The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.

Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.

It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.

The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.

Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.

Courtesy University of Alabama at Birmingham

How well does it work?

One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.

The guidelines specify that some drug regimens be modified when patients are vaccinated.

For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”

The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.

It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.

For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.

For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.

None of this advice should supersede clinical judgment, Dr. Curtis said.

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