This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

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

Analysis of finger sweat detected isoniazid in adults with tuberculosis (TB) for ≤ 6 hours after administration, based on data from a new pilot study.

Risk factors for TB treatment failure include poor medication compliance and insufficient exposure to medications, but measurement of drugs in samples of blood, saliva, or sweat can help assess adherence and inform dose adjustments, Katherine Longman, a PhD student at the University of Surrey, Guildford, England, and colleagues wrote.

Although TB is treatable, “it is well known that insufficient drug dosing leads to treatment failure and drug resistance, and so ensuring that patients have sufficient drug exposure is important,” said corresponding author Melanie J. Bailey, PhD, also of the University of Surrey.

“This can be carried out using blood, but blood is painful to collect and difficult to transport. Finger sweat offers a completely noninvasive way to sample patients,” but its use to determine medication adherence has not been examined, she said.

In a pilot study published in the International Journal of Antimicrobial Agents, the researchers reviewed data from 10 adults with TB who provided finger sweat, blood, and saliva samples at several time points ≤ 6 hours after receiving a controlled dose of isoniazid (median of 300 mg daily). They used liquid chromatography–mass spectrometry to examine the samples.

Overall, “isoniazid and acetyl isoniazid were detected in at least one finger sweat sample from all patients,” with detection rates of 96% and 77%, respectively, the researchers wrote. Given the short half-life of isoniazid, they used a window of 1-6 hours after administration. Isoniazid was consistently detected between 1 and 6 hours after administration, while acetyl isoniazid had a noticeably higher detection rate at 6 hours.

The researchers also examined creatinine to account for variability in volume of sweat samples, and found that finger sweat was significantly correlated to isoniazid concentration. The maximum isoniazid to creatinine ratio in finger sweat occurred mainly in the first hour after drug administration, and the activity of isoniazid in finger sweat over time reflected isoniazid concentration in serum more closely after normalization to creatinine, they said. The Pearson’s correlation coefficient (r) was 0.98 (P < .001; one-tailed), with normalization to creatinine, compared with r = 0.52 without normalization (P = .051).

The study findings were limited by several factors including the lack of knowledge of the last drug dose and lack of confirmation testing with an established method of analysis, the researchers noted. However, the results support the potential of the finger sweat test as a screening tool to indicate patients’ nonadherence or to identify patients at risk of low medication exposure.

“We were surprised that we were able to detect the drug in so many patient samples because the sample volume is so low, and so detection is challenging,” said Dr. Bailey. “We were also surprised that fingerprint and drug levels correlated so well after normalizing to creatinine. This is exciting as it unlocks the possibility to test drug levels, as well as providing a yes/no test.”

In practice, the finger sweat technique could reduce the burden on clinics by offering a completely noninvasive way to test a patient’s medication adherence. Looking ahead, more research is needed to explore whether creatinine normalization is widely applicable, such as whether it works for patients with abnormal kidney function, she added.
 

Noninvasive Option May Mitigate Treatment Challenges

The current study presents a strategy that might address current limitations in TB management, said Krishna Thavarajah, MD, a pulmonologist and director of the interstitial lung disease program at Henry Ford Hospital, Detroit, Michigan, in an interview.

Both self-administered treatment and directly observed therapy (DOT) for TB therapy have limitations, including adherence as low as 50% for TB regimens, she said. In addition, “DOT availability and efficacy can be limited by cost, personnel availability from an administration perspective, and by distrust of those being treated.”

In the current study, “I was struck by the correlation between the sweat and serum values of [isoniazid] and by the level of sophistication of noninvasive testing, being able to normalize for creatinine to account for different volumes of sweat,” said Dr. Thavarajah. In clinical practice, finger sweat isoniazid could potentially serve as an adjunct or alternative to DOT in patients with TB.

Although adherence to the sampling protocol and possible patient distrust of the process (such as concerns over what else is being collected in their sweat) might be barriers to the use of a finger sweat strategy in the clinical setting, appropriate patient selection, patient training, and encouraging clinicians to incorporate this testing into practice could overcome these barriers, said Dr. Thavarajah.

However, more research is needed to study the finger sweat strategy in larger, real-world samples and to study accuracy and treatment adherence with monitoring in a population undergoing DOT, she said.

The study was supported by the Engineering & Physical Sciences Research Council and by Santander PhD Mobility Awards 2019. The researchers had no financial conflicts to disclose. Dr. Thavarajah had no financial conflicts to disclose.

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

Analysis of finger sweat detected isoniazid in adults with tuberculosis (TB) for ≤ 6 hours after administration, based on data from a new pilot study.

Risk factors for TB treatment failure include poor medication compliance and insufficient exposure to medications, but measurement of drugs in samples of blood, saliva, or sweat can help assess adherence and inform dose adjustments, Katherine Longman, a PhD student at the University of Surrey, Guildford, England, and colleagues wrote.

Although TB is treatable, “it is well known that insufficient drug dosing leads to treatment failure and drug resistance, and so ensuring that patients have sufficient drug exposure is important,” said corresponding author Melanie J. Bailey, PhD, also of the University of Surrey.

“This can be carried out using blood, but blood is painful to collect and difficult to transport. Finger sweat offers a completely noninvasive way to sample patients,” but its use to determine medication adherence has not been examined, she said.

In a pilot study published in the International Journal of Antimicrobial Agents, the researchers reviewed data from 10 adults with TB who provided finger sweat, blood, and saliva samples at several time points ≤ 6 hours after receiving a controlled dose of isoniazid (median of 300 mg daily). They used liquid chromatography–mass spectrometry to examine the samples.

Overall, “isoniazid and acetyl isoniazid were detected in at least one finger sweat sample from all patients,” with detection rates of 96% and 77%, respectively, the researchers wrote. Given the short half-life of isoniazid, they used a window of 1-6 hours after administration. Isoniazid was consistently detected between 1 and 6 hours after administration, while acetyl isoniazid had a noticeably higher detection rate at 6 hours.

The researchers also examined creatinine to account for variability in volume of sweat samples, and found that finger sweat was significantly correlated to isoniazid concentration. The maximum isoniazid to creatinine ratio in finger sweat occurred mainly in the first hour after drug administration, and the activity of isoniazid in finger sweat over time reflected isoniazid concentration in serum more closely after normalization to creatinine, they said. The Pearson’s correlation coefficient (r) was 0.98 (P < .001; one-tailed), with normalization to creatinine, compared with r = 0.52 without normalization (P = .051).

The study findings were limited by several factors including the lack of knowledge of the last drug dose and lack of confirmation testing with an established method of analysis, the researchers noted. However, the results support the potential of the finger sweat test as a screening tool to indicate patients’ nonadherence or to identify patients at risk of low medication exposure.

“We were surprised that we were able to detect the drug in so many patient samples because the sample volume is so low, and so detection is challenging,” said Dr. Bailey. “We were also surprised that fingerprint and drug levels correlated so well after normalizing to creatinine. This is exciting as it unlocks the possibility to test drug levels, as well as providing a yes/no test.”

In practice, the finger sweat technique could reduce the burden on clinics by offering a completely noninvasive way to test a patient’s medication adherence. Looking ahead, more research is needed to explore whether creatinine normalization is widely applicable, such as whether it works for patients with abnormal kidney function, she added.
 

Noninvasive Option May Mitigate Treatment Challenges

The current study presents a strategy that might address current limitations in TB management, said Krishna Thavarajah, MD, a pulmonologist and director of the interstitial lung disease program at Henry Ford Hospital, Detroit, Michigan, in an interview.

Both self-administered treatment and directly observed therapy (DOT) for TB therapy have limitations, including adherence as low as 50% for TB regimens, she said. In addition, “DOT availability and efficacy can be limited by cost, personnel availability from an administration perspective, and by distrust of those being treated.”

In the current study, “I was struck by the correlation between the sweat and serum values of [isoniazid] and by the level of sophistication of noninvasive testing, being able to normalize for creatinine to account for different volumes of sweat,” said Dr. Thavarajah. In clinical practice, finger sweat isoniazid could potentially serve as an adjunct or alternative to DOT in patients with TB.

Although adherence to the sampling protocol and possible patient distrust of the process (such as concerns over what else is being collected in their sweat) might be barriers to the use of a finger sweat strategy in the clinical setting, appropriate patient selection, patient training, and encouraging clinicians to incorporate this testing into practice could overcome these barriers, said Dr. Thavarajah.

However, more research is needed to study the finger sweat strategy in larger, real-world samples and to study accuracy and treatment adherence with monitoring in a population undergoing DOT, she said.

The study was supported by the Engineering & Physical Sciences Research Council and by Santander PhD Mobility Awards 2019. The researchers had no financial conflicts to disclose. Dr. Thavarajah had no financial conflicts to disclose.

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

Analysis of finger sweat detected isoniazid in adults with tuberculosis (TB) for ≤ 6 hours after administration, based on data from a new pilot study.

Risk factors for TB treatment failure include poor medication compliance and insufficient exposure to medications, but measurement of drugs in samples of blood, saliva, or sweat can help assess adherence and inform dose adjustments, Katherine Longman, a PhD student at the University of Surrey, Guildford, England, and colleagues wrote.

Although TB is treatable, “it is well known that insufficient drug dosing leads to treatment failure and drug resistance, and so ensuring that patients have sufficient drug exposure is important,” said corresponding author Melanie J. Bailey, PhD, also of the University of Surrey.

“This can be carried out using blood, but blood is painful to collect and difficult to transport. Finger sweat offers a completely noninvasive way to sample patients,” but its use to determine medication adherence has not been examined, she said.

In a pilot study published in the International Journal of Antimicrobial Agents, the researchers reviewed data from 10 adults with TB who provided finger sweat, blood, and saliva samples at several time points ≤ 6 hours after receiving a controlled dose of isoniazid (median of 300 mg daily). They used liquid chromatography–mass spectrometry to examine the samples.

Overall, “isoniazid and acetyl isoniazid were detected in at least one finger sweat sample from all patients,” with detection rates of 96% and 77%, respectively, the researchers wrote. Given the short half-life of isoniazid, they used a window of 1-6 hours after administration. Isoniazid was consistently detected between 1 and 6 hours after administration, while acetyl isoniazid had a noticeably higher detection rate at 6 hours.

The researchers also examined creatinine to account for variability in volume of sweat samples, and found that finger sweat was significantly correlated to isoniazid concentration. The maximum isoniazid to creatinine ratio in finger sweat occurred mainly in the first hour after drug administration, and the activity of isoniazid in finger sweat over time reflected isoniazid concentration in serum more closely after normalization to creatinine, they said. The Pearson’s correlation coefficient (r) was 0.98 (P < .001; one-tailed), with normalization to creatinine, compared with r = 0.52 without normalization (P = .051).

The study findings were limited by several factors including the lack of knowledge of the last drug dose and lack of confirmation testing with an established method of analysis, the researchers noted. However, the results support the potential of the finger sweat test as a screening tool to indicate patients’ nonadherence or to identify patients at risk of low medication exposure.

“We were surprised that we were able to detect the drug in so many patient samples because the sample volume is so low, and so detection is challenging,” said Dr. Bailey. “We were also surprised that fingerprint and drug levels correlated so well after normalizing to creatinine. This is exciting as it unlocks the possibility to test drug levels, as well as providing a yes/no test.”

In practice, the finger sweat technique could reduce the burden on clinics by offering a completely noninvasive way to test a patient’s medication adherence. Looking ahead, more research is needed to explore whether creatinine normalization is widely applicable, such as whether it works for patients with abnormal kidney function, she added.
 

Noninvasive Option May Mitigate Treatment Challenges

The current study presents a strategy that might address current limitations in TB management, said Krishna Thavarajah, MD, a pulmonologist and director of the interstitial lung disease program at Henry Ford Hospital, Detroit, Michigan, in an interview.

Both self-administered treatment and directly observed therapy (DOT) for TB therapy have limitations, including adherence as low as 50% for TB regimens, she said. In addition, “DOT availability and efficacy can be limited by cost, personnel availability from an administration perspective, and by distrust of those being treated.”

In the current study, “I was struck by the correlation between the sweat and serum values of [isoniazid] and by the level of sophistication of noninvasive testing, being able to normalize for creatinine to account for different volumes of sweat,” said Dr. Thavarajah. In clinical practice, finger sweat isoniazid could potentially serve as an adjunct or alternative to DOT in patients with TB.

Although adherence to the sampling protocol and possible patient distrust of the process (such as concerns over what else is being collected in their sweat) might be barriers to the use of a finger sweat strategy in the clinical setting, appropriate patient selection, patient training, and encouraging clinicians to incorporate this testing into practice could overcome these barriers, said Dr. Thavarajah.

However, more research is needed to study the finger sweat strategy in larger, real-world samples and to study accuracy and treatment adherence with monitoring in a population undergoing DOT, she said.

The study was supported by the Engineering & Physical Sciences Research Council and by Santander PhD Mobility Awards 2019. The researchers had no financial conflicts to disclose. Dr. Thavarajah had no financial conflicts to disclose.

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

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

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].

I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

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].

I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

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].

TOPLINE:

More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however, follow-up visits and new antibiotic dispensations were rare regardless of treatment, suggesting that not receiving antibiotics may not lead to additional health care use.

METHODOLOGY:

• Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
• This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
• The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
• The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.

TAKEAWAY:

• Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
• Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
• Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
• Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.

IN PRACTICE:

“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.

SOURCE:

The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.

LIMITATIONS:

The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.

DISCLOSURES:

This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however, follow-up visits and new antibiotic dispensations were rare regardless of treatment, suggesting that not receiving antibiotics may not lead to additional health care use.

METHODOLOGY:

• Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
• This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
• The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
• The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.

TAKEAWAY:

• Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
• Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
• Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
• Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.

IN PRACTICE:

“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.

SOURCE:

The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.

LIMITATIONS:

The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.

DISCLOSURES:

This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

More than two thirds of children with conjunctivitis received antibiotics within a day of their initial ambulatory care visit; however, follow-up visits and new antibiotic dispensations were rare regardless of treatment, suggesting that not receiving antibiotics may not lead to additional health care use.

METHODOLOGY:

• Researchers evaluated the frequency of topical antibiotic treatment and its association with subsequent health care use among commercially insured children with acute infectious conjunctivitis in the United States.
• This cohort study analyzed data from the 2021 MarketScan Commercial Claims and Encounters Database, including 44,793 children with conjunctivitis (median age, 5 years; 47% girls) and ambulatory care encounters.
• The primary exposure was a topical antibiotic prescription dispensed within 1 day of an ambulatory care visit, with outcomes assessed 2-14 days after the visit.
• The primary outcomes were ambulatory care revisits for conjunctivitis and same-day dispensation of a new topical antibiotic, and secondary outcomes included emergency department revisits and hospitalizations.

TAKEAWAY:

• Topical antibiotics were dispensed within a day of an ambulatory care visit in 69% of the cases; however, they were less frequently dispensed following visits to eye clinics (34%), for children aged 6-11 years (66%), and for those with viral conjunctivitis (28%).
• Ambulatory care revisits for conjunctivitis within 2 weeks occurred in only 3.2% of children who had received antibiotics (adjusted odds ratio [aOR], 1.11; 95% CI, 0.99-1.25).
• Similarly, revisits with same-day dispensation of a new antibiotic were also rare (1.4%), with no significant association between antibiotic treatment and revisits (aOR, 1.10; 95% CI, 0.92-1.33).
• Hospitalizations for conjunctivitis occurred in 0.03% of cases, and emergency department revisits occurred in 0.12%, with no differences between children who received antibiotics and those who did not.

IN PRACTICE:

“Given that antibiotics may not be associated with improved outcomes or change in subsequent health care use and are associated with adverse effects and antibiotic resistance, efforts to reduce overtreatment of acute infectious conjunctivitis are warranted,” the authors wrote.

SOURCE:

The study was led by Daniel J. Shapiro, MD, MPH, of the Department of Emergency Medicine at the University of California, San Francisco, and published online on June 27, 2024, in JAMA Ophthalmology.

LIMITATIONS:

The major limitations of the study included the inability to distinguish scheduled visits from unscheduled revisits, incomplete clinical data such as rare complications of conjunctivitis, and the inability to confirm the accuracy of the coded diagnosis of infectious conjunctivitis, especially in children who did not receive a thorough eye examination.

DISCLOSURES:

This study did not declare receiving funding from any sources. One author reported receiving grants from several sources outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

LYON, FRANCE — The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

“Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups,” said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women’s Hospital, Boston, but “with increased high-sensitivity CRP reductions in those receiving semaglutide.”

The drug also “significantly reduced high-sensitivity CRP early,” he said, “prior to major weight loss and in those who did not lose significant amounts of weight.” The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss “was still quite modest,” at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, said in an interview that body weight “is probably the major driver” of CRP levels in the population, accounting for between 20% and 30% of the variation.

Dr. Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: “Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?”
 

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. “All it tells us is about associations.”

“What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes,” he said.

Dr. Sattar also took issue with the researchers’ conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the “pattern of CRP reduction and weight reduction is almost identical.”

Dr. Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, “speculation.”

Dr. Plutzky said that “systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity,” and high-sensitivity CRP levels are an “established biomarker of inflammation and have been shown to predict cardiovascular risk.”

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity “remains incompletely understood,” said Dr. Plutzky.
 

A version of this article appeared on Medscape.com.

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

More than 1.5 million Americans are diagnosed with an incidental CT scan-detected lung nodule annually. Advanced bronchoscopy, as a diagnostic tool for evaluation of these nodules, has evolved rapidly, incorporating a range of techniques and tools beyond CT scan-guided biopsies to assess peripheral lesions. The primary goal is to provide patients with accurate benign or malignant diagnoses. However, accurately determining the effectiveness of innovative technologies in providing a diagnosis remains challenging, in part due to limitations in study design and outcome reporting, along with the scarcity of comparative and randomized controlled studies.^1,2 Current literature shows significant variability in diagnostic yield definition, lacking generalizability.

CHEST

To address this issue, an official research statement by the American Thoracic Society and CHEST defines the diagnostic yield as “the proportion of all individuals undergoing the diagnostic procedure under evaluation in whom a specific malignant or benign diagnosis is established.”³ To achieve this measure, the numerator includes all patients with lung nodules in whom the result of a diagnostic procedure establishes a specific benign or malignant diagnosis that is readily sufficient to inform patient care without additional diagnostic workup, and the denominator should include all patients in whom the procedure was attempted or performed. This standardized definition is crucial for ensuring consistency across studies, allowing for comparison or pooling of results, enhancing the reliability of diagnostic yield data, and informing clinical decisions.

CHEST

References

1. Tanner NT, Yarmus L, Chen A, et al. Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial. Chest. 2018;154(5):1035-1043.

2. Ost DE, Ernst A, Lei X, et al. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE Registry. Am J Resp Crit Care Med. 2016;193(1):68-77.

3. Gonzalez AV, Silvestri GA, Korevaar DA, et al. Assessment of advanced diagnostic bronchoscopy outcomes for peripheral lung lesions: a Delphi consensus definition of diagnostic yield and recommendations for patient-centered study designs. An official American Thoracic Society/American College of Chest Physicians research statement. Am J Respir Crit Care Med. 2024;209(6):634-646.

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

More than 1.5 million Americans are diagnosed with an incidental CT scan-detected lung nodule annually. Advanced bronchoscopy, as a diagnostic tool for evaluation of these nodules, has evolved rapidly, incorporating a range of techniques and tools beyond CT scan-guided biopsies to assess peripheral lesions. The primary goal is to provide patients with accurate benign or malignant diagnoses. However, accurately determining the effectiveness of innovative technologies in providing a diagnosis remains challenging, in part due to limitations in study design and outcome reporting, along with the scarcity of comparative and randomized controlled studies.^1,2 Current literature shows significant variability in diagnostic yield definition, lacking generalizability.

CHEST

To address this issue, an official research statement by the American Thoracic Society and CHEST defines the diagnostic yield as “the proportion of all individuals undergoing the diagnostic procedure under evaluation in whom a specific malignant or benign diagnosis is established.”³ To achieve this measure, the numerator includes all patients with lung nodules in whom the result of a diagnostic procedure establishes a specific benign or malignant diagnosis that is readily sufficient to inform patient care without additional diagnostic workup, and the denominator should include all patients in whom the procedure was attempted or performed. This standardized definition is crucial for ensuring consistency across studies, allowing for comparison or pooling of results, enhancing the reliability of diagnostic yield data, and informing clinical decisions.

CHEST

References

1. Tanner NT, Yarmus L, Chen A, et al. Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial. Chest. 2018;154(5):1035-1043.

2. Ost DE, Ernst A, Lei X, et al. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE Registry. Am J Resp Crit Care Med. 2016;193(1):68-77.

3. Gonzalez AV, Silvestri GA, Korevaar DA, et al. Assessment of advanced diagnostic bronchoscopy outcomes for peripheral lung lesions: a Delphi consensus definition of diagnostic yield and recommendations for patient-centered study designs. An official American Thoracic Society/American College of Chest Physicians research statement. Am J Respir Crit Care Med. 2024;209(6):634-646.

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

More than 1.5 million Americans are diagnosed with an incidental CT scan-detected lung nodule annually. Advanced bronchoscopy, as a diagnostic tool for evaluation of these nodules, has evolved rapidly, incorporating a range of techniques and tools beyond CT scan-guided biopsies to assess peripheral lesions. The primary goal is to provide patients with accurate benign or malignant diagnoses. However, accurately determining the effectiveness of innovative technologies in providing a diagnosis remains challenging, in part due to limitations in study design and outcome reporting, along with the scarcity of comparative and randomized controlled studies.^1,2 Current literature shows significant variability in diagnostic yield definition, lacking generalizability.

CHEST

To address this issue, an official research statement by the American Thoracic Society and CHEST defines the diagnostic yield as “the proportion of all individuals undergoing the diagnostic procedure under evaluation in whom a specific malignant or benign diagnosis is established.”³ To achieve this measure, the numerator includes all patients with lung nodules in whom the result of a diagnostic procedure establishes a specific benign or malignant diagnosis that is readily sufficient to inform patient care without additional diagnostic workup, and the denominator should include all patients in whom the procedure was attempted or performed. This standardized definition is crucial for ensuring consistency across studies, allowing for comparison or pooling of results, enhancing the reliability of diagnostic yield data, and informing clinical decisions.

CHEST

References

1. Tanner NT, Yarmus L, Chen A, et al. Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial. Chest. 2018;154(5):1035-1043.

2. Ost DE, Ernst A, Lei X, et al. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE Registry. Am J Resp Crit Care Med. 2016;193(1):68-77.

3. Gonzalez AV, Silvestri GA, Korevaar DA, et al. Assessment of advanced diagnostic bronchoscopy outcomes for peripheral lung lesions: a Delphi consensus definition of diagnostic yield and recommendations for patient-centered study designs. An official American Thoracic Society/American College of Chest Physicians research statement. Am J Respir Crit Care Med. 2024;209(6):634-646.

SLEEP MEDICINE NETWORK

Nonrespiratory Sleep Section

There has been a recent interest in post–intensive care syndrome (PICS), as an increasing number of patients are surviving critical illness. PICS is defined as “new onset or worsening of impairments in physical, cognitive, and/or mental health that arises after an ICU stay and persists beyond hospital discharge.¹ We know that poor sleep is a common occurrence in the ICU, which can contribute to cognitive impairment and could be due to various risk factors, including age, individual comorbidities, reason for admission, and ICU interventions.² Sleep impairment after hospital discharge is highly prevalent for up to 1 year after hospitalization.

CHEST

The most common sleep impairment described after hospital discharge from the ICU is insomnia, which coexists with anxiety, depression, and posttraumatic stress disorder.³ When patients are seen in a post-ICU clinic, a multimodal strategy is needed for the treatment of insomnia, which includes practicing good sleep hygiene, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy if indicated.

CHEST

References

1. Rawal G, Yadav S, Kumar R. Post-intensive care syndrome: an overview. J Transl Int Med. 2017;5(2):90-92.

2. Zampieri FG, et al. Ann Am Thorac Soc. 2023;20(11):1558-1560.

3. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468.

4. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(2):255-262.

SLEEP MEDICINE NETWORK

Nonrespiratory Sleep Section

There has been a recent interest in post–intensive care syndrome (PICS), as an increasing number of patients are surviving critical illness. PICS is defined as “new onset or worsening of impairments in physical, cognitive, and/or mental health that arises after an ICU stay and persists beyond hospital discharge.¹ We know that poor sleep is a common occurrence in the ICU, which can contribute to cognitive impairment and could be due to various risk factors, including age, individual comorbidities, reason for admission, and ICU interventions.² Sleep impairment after hospital discharge is highly prevalent for up to 1 year after hospitalization.

CHEST

The most common sleep impairment described after hospital discharge from the ICU is insomnia, which coexists with anxiety, depression, and posttraumatic stress disorder.³ When patients are seen in a post-ICU clinic, a multimodal strategy is needed for the treatment of insomnia, which includes practicing good sleep hygiene, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy if indicated.

CHEST

References

1. Rawal G, Yadav S, Kumar R. Post-intensive care syndrome: an overview. J Transl Int Med. 2017;5(2):90-92.

2. Zampieri FG, et al. Ann Am Thorac Soc. 2023;20(11):1558-1560.

3. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468.

4. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(2):255-262.

SLEEP MEDICINE NETWORK

Nonrespiratory Sleep Section

There has been a recent interest in post–intensive care syndrome (PICS), as an increasing number of patients are surviving critical illness. PICS is defined as “new onset or worsening of impairments in physical, cognitive, and/or mental health that arises after an ICU stay and persists beyond hospital discharge.¹ We know that poor sleep is a common occurrence in the ICU, which can contribute to cognitive impairment and could be due to various risk factors, including age, individual comorbidities, reason for admission, and ICU interventions.² Sleep impairment after hospital discharge is highly prevalent for up to 1 year after hospitalization.

CHEST

The most common sleep impairment described after hospital discharge from the ICU is insomnia, which coexists with anxiety, depression, and posttraumatic stress disorder.³ When patients are seen in a post-ICU clinic, a multimodal strategy is needed for the treatment of insomnia, which includes practicing good sleep hygiene, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy if indicated.

CHEST

References

1. Rawal G, Yadav S, Kumar R. Post-intensive care syndrome: an overview. J Transl Int Med. 2017;5(2):90-92.

2. Zampieri FG, et al. Ann Am Thorac Soc. 2023;20(11):1558-1560.

3. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical illness: a systematic review. Ann Am Thorac Soc. 2017;14(9):1457-1468.

4. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(2):255-262.

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILDs) are a diverse group of relentlessly progressive fibroinflammatory disorders. Pharmacotherapy includes antifibrotics and immunosuppressants as foundational strategies to mitigate loss of lung function. There has been a growing interest in telomere length and its response to immunosuppression in the ILD community.

CHEST

Telomeres are repetitive nucleotide sequences that “cap” chromosomes and protect against chromosomal shortening during cell replication. Genetic and environmental factors can lead to premature shortening of telomeres. Once a critical length is reached, the cell enters senescence. Short telomere length has been linked to rapid progression, worse outcomes, and poor response to immunosuppressants in idiopathic pulmonary fibrosis (IPF).

CHEST

References

1. Zhang D, Adegunsoye A, Oldham JM, et al. Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease. Eur Respir J. 2023;62(5):2300441.

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILDs) are a diverse group of relentlessly progressive fibroinflammatory disorders. Pharmacotherapy includes antifibrotics and immunosuppressants as foundational strategies to mitigate loss of lung function. There has been a growing interest in telomere length and its response to immunosuppression in the ILD community.

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Telomeres are repetitive nucleotide sequences that “cap” chromosomes and protect against chromosomal shortening during cell replication. Genetic and environmental factors can lead to premature shortening of telomeres. Once a critical length is reached, the cell enters senescence. Short telomere length has been linked to rapid progression, worse outcomes, and poor response to immunosuppressants in idiopathic pulmonary fibrosis (IPF).

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References

1. Zhang D, Adegunsoye A, Oldham JM, et al. Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease. Eur Respir J. 2023;62(5):2300441.

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILDs) are a diverse group of relentlessly progressive fibroinflammatory disorders. Pharmacotherapy includes antifibrotics and immunosuppressants as foundational strategies to mitigate loss of lung function. There has been a growing interest in telomere length and its response to immunosuppression in the ILD community.

CHEST

Telomeres are repetitive nucleotide sequences that “cap” chromosomes and protect against chromosomal shortening during cell replication. Genetic and environmental factors can lead to premature shortening of telomeres. Once a critical length is reached, the cell enters senescence. Short telomere length has been linked to rapid progression, worse outcomes, and poor response to immunosuppressants in idiopathic pulmonary fibrosis (IPF).

CHEST

References

1. Zhang D, Adegunsoye A, Oldham JM, et al. Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease. Eur Respir J. 2023;62(5):2300441.