Mixed Topics

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Alpha-gal syndrome (AGS) is commonly described as an allergy to red meat, but that is “just the beginning,” allergist and immunologist Scott P. Commins, MD, PhD, told attendees at the annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting.

Dr. Commins, associate chief for allergy and immunology at the University of North Carolina at Chapel Hill, has made alpha-gal, a potentially fatal allergy, which, in the United States is tied to the bite of the Lone Star tick, his primary research focus.

Beyond red meat, “there are some people who are allergic to all things mammal,” he explained. Dairy products from mammals, medical devices made from mammalian products, vaccines and medicines that contain gelatin, and even commercial products such as perfumes and cosmetics may be behind an AGS reaction.

“The derived products from pigs and cows really find their way into a lot of our day-to-day products,” he said. “I try to keep an open mind about these exposures.”

Physicians should also be aware that “this can happen to kids,” said Dr. Commins. “It looks very similar to adults’ [AGS]. They can end up in the emergency department.”

He also had clinical advice about food challenges for AGS. He explained that there’s more alpha-gal in beef than in other red meats (including pork, venison, and lamb) with the exception of pork kidney. Pork kidney, he said, “has the most alpha-gal that we can find in the lab.”

Dr. Commins said he has stopped using beef for AGS food challenges and has switched to pork sausage patties with a high fat content microwaved in the clinic because they have less alpha-gal in general and he views them as safer.

Long delay in symptom onset

AGS symptoms typically take 2-6 hours to appear after eating red meat or being exposed to mammalian products, but Dr. Commins related a story about a patient he sent home who had very mild symptoms (some lower back itching) after he had spent the day at the clinic after a pork sausage food challenge for AGS.

The patient had returned home. Eight hours after the food challenge, his wife sent Dr. Commins a picture of her husband’s back, which was riddled with welts and was itching badly.

“I learned that if you’re going to do these food challenges, if there is a hint of symptoms at the clinic at 6 hours, keep them in the clinic, because it may really take that long to evolve,” Dr. Commins said.

One of the early signs he’s discovered is palmar erythema (redness and swelling of the hands).

Research has shown that AGS has been heavily concentrated in the Southeast, where Lone Star tick populations are clustered, but research has shown that from 2017 to 2022, it moved up the East Coast to the central United States and Upper Midwest.

“We are seeing increasing diagnoses of AGS in places that are not, perhaps, where we first thought this allergy existed,” said Dr. Commins. “Stay aware,” he cautioned.

The allergy is not exclusive to the United States, he noted. In Europe and Australia, for example, AGS is not thought to be tied to the Lone Star tick, which doesn’t inhabit those regions.

“It is a global phenomenon,” Dr. Commins said.

In August, the CDC alerted physicians to emerging cases of alpha-gal allergy after an article in Morbidity and Mortality Weekly Report indicated that health care providers have little knowledge about the allergy. Of the 1,500 health care providers surveyed, 42% had never heard of the syndrome, and another 35% were not confident in diagnosing or managing affected patients.

Matthew Lau, MD, an allergist with Kaiser Permanente in Honolulu who listened to Dr. Commins’ talk, told this news organization, “It’s important to raise awareness in primary care particularly, he said, as “allergists see only a fraction of the [AGS] patients.”

Allergists can help raise awareness

“Allergists have a role to alert the general community” and to drive more referrals, he said. That includes emergency departments, where physicians commonly see anaphylaxis.

Dr. Lau said he expects the incidence of AGS to increase, because global warming will likely lengthen warmer seasons and cause the geographic distribution to change.

Jay Lieberman, MD, a pediatric allergist at Le Bonheur Children’s Hospital in Memphis, Tenn., told this news organization, “There’s still a lot of confusion, and hearing from an expert like Dr. Commins helps tease out the not-obvious things about patients who are having more mild symptoms,” such as from allergy to dairy or medicines or vaccines that contain gelatin.

As a pediatric allergist, Dr. Lieberman said he sees less alpha-gal than his colleagues, but, he said, “On the adult side in Tennessee, it’s rampant.”

Dr. Commins, Dr. Lieberman, and Dr. Lau report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ILLUSTRATIVE CASE

A 9-year-old girl presents to your urgent care clinic after a fall while snowboarding for the first time. She reports falling forward onto her outstretched right hand and describes pain in her distal right forearm. She denies paresthesias, weakness, or lacerations. Physical examination reveals mild edema of the dorsal aspect of her distal right forearm and tenderness to palpation of the dorsal aspect of her distal radius. She denies tenderness to palpation of her ulna, anatomic snuffbox, hand, and elbow. Range of motion of the wrist is full on passive testing, but she declines active testing due to pain. Wrist radiographs reveal an uncomplicated torus fracture of the distal radius. Can immobilization with a soft bandage alone sufficiently treat this fracture?

Fractures of the distal radius are among the most common fractures of the upper extremity and commonly occur from a fall onto an outstretched hand.² In the pediatric population, torus fractures, also known as buckle fractures, are the most common type of distal radius fracture, comprising an estimated 50% of pediatric wrist fractures.^3,4 This is due to the presence of a physeal growth plate, thicker periosteum, and softer underlying bone in pediatric patients.^4,5 When an axial load is applied, as in a fall onto an outstretched hand, the force can lead to plastic deformation, with or without cortical disruption of the bone.^4,5

Pediatric torus fractures of the distal radius generally are treated with immobilization,² traditionally through a short arm cast or a removable, rigid wrist splint.^2,6 The wrist often is immobilized for 3 to 4 weeks, with routine follow-up and potential repeat plain film radiography to ensure stability.^2,6

Despite common use of immobilization, torus fractures of the distal radius are anatomically stable, and displacement is unlikely to occur.^7,8 As such, many studies have suggested that treatment of torus fractures with rigid immobilization in a cast or splint may not be necessary.^9,10 However, a 2018 Cochrane review concluded that the quality of evidence illustrating similar recovery between treatments was low, leaving uncertainty as to the most appropriate management strategy.⁶ Less casting and follow-up imaging could have positive implications for patient satisfaction, health care–associated costs, and radiation exposure.¹⁰

This study, the Forearm Fracture Recovery in Children Evaluation (FORCE) trial, compared the traditional treatment of distal radius torus fractures with rigid immobilization to soft immobilization and immediate discharge.

STUDY SUMMARY

Providing quality evidence for a standard of care

FORCE was a randomized controlled equivalence trial (N = 965) across 23 emergency departments (EDs) in the United Kingdom that compared pain and function in pediatric patients with distal radius torus fractures treated with a soft bandage and immediate discharge vs rigid immobilization and routine follow-up.¹ Patients included children ages 4 to 15 years presenting to the ED with a distal radius torus fracture, which was confirmed radiologically.

At 3 days, pain scores improved by 3.2 points in the soft bandage group and 3.1 points in the rigid immobilization group.

Patients with concomitant ipsilateral ulnar fractures were included in the study. Researchers excluded patients with injuries older than 36 hours, evidence of cortical disruption on radiograph (eg, greenstick fracture), or additional fractures other than the wrist, or those who were deemed unable to follow up with the full study protocol (eg, having insufficient English comprehension).

Continue to: Patients were randomly assigned...

Patients were randomly assigned in a 1:1 ratio to receive treatment with either a soft bandage such as a gauze roller bandage (n = 489) or rigid immobilization (n = 476). For patients in the bandage group, a soft bandage was applied in the ED or provided for home application without planned clinical follow-up. Patients in the rigid immobilization group were treated in the ED with either a removable manufactured splint or a molded splint or cast, followed by the standard follow-up practice of the treating center. Patients in the soft bandage group were advised not to wear the bandage for more than 3 weeks. Blinding was not possible, but the treatment team did not take part in patient follow-up.

The primary outcome was change in pain 3 days after treatment, measured on the Wong-Baker FACES Pain Rating Scale (an ordinal assessment using 6 illustrated facial expressions translated to a numeric rating on a scale of 0-10, with higher scores indicating worse pain). This scale has an established minimum clinically important difference (MCID) value of 1 face (2 points).¹¹ Per standard practice in equivalence trials, the equivalence margin was defined as half the MCID, with a value of 1.0 used in this study.

Secondary outcomes measured over the 6-week follow-up period included additional pain measurements using the Wong-Baker scale, measures of function and health-­related quality of life, analgesia use, days of absence from school or childcare, complication rates, and patient satisfaction. This study used modified intention-to-treat and per-protocol analyses.

The mean age of participants was 9.6 years; 39% were girls and 61% were boys. In the bandage group, 94% opted to have the soft bandage applied in the ED, and 95% of the rigid immobilization group were treated with a removable wrist splint in the ED. At 3 days, pain scores improved by 3.2 points (standard deviation [SD] = 2.1) in the soft bandage group and 3.1 points (SD = 2.1) in the rigid immobilization group. The adjusted difference was –0.1 (95% CI, –0.37 to 0.17) in the intention-to-treat analysis and –0.06 (95% CI, –0.34 to 0.21) in the per-protocol analysis, which were both less than the predetermined equivalence margin. This equivalence margin also was met at all secondary time points (1 day, 7 days, 3 weeks, and 6 weeks after treatment) and in subgroup analysis of those 4 to 7 years and 8 to 15 years.

Use of any analgesia in the prior 24 hours was slightly higher in the soft bandage group on Day 1 (83% vs 78%; P = .04) and Day 3 (57% vs 51%; P = .05), but this difference was not seen on Day 7. Satisfaction, measured via a 7-point Likert scale (range from “extremely satisfied” to “extremely unsatisfied”), was slightly lower in the soft bandage group on Day 1 (median 2 [interquartile range = 1, 2] vs median 1 [interquartile range = 1, 2]; P < .0001) but was not different after 6 weeks. There were no measured differences in any other secondary outcomes, including function, quality of life, and complication rates.

Continue to: By the primary end point...

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

By the primary end point of 3 days, 36 patients (7%) in the soft bandage group returned to medical care requesting a change to rigid immobilization, compared with 1 patient (0.2%) in the rigid immobilization group declining intervention.

WHAT’S NEW

Equivalence in pain and function scores

This trial showed equivalence in pain at 3 days’ follow-up in children with distal radius torus fractures who were offered bandaging and then immediately discharged from the ED, compared with rigid immobilization and clinical follow-up. There were no significant differences in pain or function between groups during the 6 weeks following the initial injury. De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of these fractures.

CAVEATS

Lack of masking likely introduced bias

There are no major caveats associated with managing distal radius torus fractures with a soft bandage and discharge from the ED, compared with the traditional treatment of rigid immobilization. However, bias was likely introduced in patient-reported outcomes due to the inability to mask patients and families to the treatment allocation. This may have led to overstating the severity of outcomes in the bandage group, given the strong preference for rigid immobilization, although equivalence was illustrated despite this potential bias.

CHALLENGES TO IMPLEMENTATION

Preferences may be difficult to change

Parents and clinicians demonstrated a preference for rigid immobilization, as shown in the imbalance in treatment crossovers, with 7% of children changing to the rigid immobilization group by the primary study end point of 3 days. The study authors hypothesized that crossovers may have been due to the perception by some parents that rigid immobilization is the gold standard of treatment, as well as clinicians’ seeking to escalate care for patients returning for follow-up. Policy and guideline changes, as well as physician efforts to educate patients on outcomes with soft bandage treatment, are likely to improve these misconceptions.

ILLUSTRATIVE CASE

A 9-year-old girl presents to your urgent care clinic after a fall while snowboarding for the first time. She reports falling forward onto her outstretched right hand and describes pain in her distal right forearm. She denies paresthesias, weakness, or lacerations. Physical examination reveals mild edema of the dorsal aspect of her distal right forearm and tenderness to palpation of the dorsal aspect of her distal radius. She denies tenderness to palpation of her ulna, anatomic snuffbox, hand, and elbow. Range of motion of the wrist is full on passive testing, but she declines active testing due to pain. Wrist radiographs reveal an uncomplicated torus fracture of the distal radius. Can immobilization with a soft bandage alone sufficiently treat this fracture?

Fractures of the distal radius are among the most common fractures of the upper extremity and commonly occur from a fall onto an outstretched hand.² In the pediatric population, torus fractures, also known as buckle fractures, are the most common type of distal radius fracture, comprising an estimated 50% of pediatric wrist fractures.^3,4 This is due to the presence of a physeal growth plate, thicker periosteum, and softer underlying bone in pediatric patients.^4,5 When an axial load is applied, as in a fall onto an outstretched hand, the force can lead to plastic deformation, with or without cortical disruption of the bone.^4,5

Pediatric torus fractures of the distal radius generally are treated with immobilization,² traditionally through a short arm cast or a removable, rigid wrist splint.^2,6 The wrist often is immobilized for 3 to 4 weeks, with routine follow-up and potential repeat plain film radiography to ensure stability.^2,6

Despite common use of immobilization, torus fractures of the distal radius are anatomically stable, and displacement is unlikely to occur.^7,8 As such, many studies have suggested that treatment of torus fractures with rigid immobilization in a cast or splint may not be necessary.^9,10 However, a 2018 Cochrane review concluded that the quality of evidence illustrating similar recovery between treatments was low, leaving uncertainty as to the most appropriate management strategy.⁶ Less casting and follow-up imaging could have positive implications for patient satisfaction, health care–associated costs, and radiation exposure.¹⁰

This study, the Forearm Fracture Recovery in Children Evaluation (FORCE) trial, compared the traditional treatment of distal radius torus fractures with rigid immobilization to soft immobilization and immediate discharge.

STUDY SUMMARY

Providing quality evidence for a standard of care

FORCE was a randomized controlled equivalence trial (N = 965) across 23 emergency departments (EDs) in the United Kingdom that compared pain and function in pediatric patients with distal radius torus fractures treated with a soft bandage and immediate discharge vs rigid immobilization and routine follow-up.¹ Patients included children ages 4 to 15 years presenting to the ED with a distal radius torus fracture, which was confirmed radiologically.

At 3 days, pain scores improved by 3.2 points in the soft bandage group and 3.1 points in the rigid immobilization group.

Patients with concomitant ipsilateral ulnar fractures were included in the study. Researchers excluded patients with injuries older than 36 hours, evidence of cortical disruption on radiograph (eg, greenstick fracture), or additional fractures other than the wrist, or those who were deemed unable to follow up with the full study protocol (eg, having insufficient English comprehension).

Continue to: Patients were randomly assigned...

Patients were randomly assigned in a 1:1 ratio to receive treatment with either a soft bandage such as a gauze roller bandage (n = 489) or rigid immobilization (n = 476). For patients in the bandage group, a soft bandage was applied in the ED or provided for home application without planned clinical follow-up. Patients in the rigid immobilization group were treated in the ED with either a removable manufactured splint or a molded splint or cast, followed by the standard follow-up practice of the treating center. Patients in the soft bandage group were advised not to wear the bandage for more than 3 weeks. Blinding was not possible, but the treatment team did not take part in patient follow-up.

The primary outcome was change in pain 3 days after treatment, measured on the Wong-Baker FACES Pain Rating Scale (an ordinal assessment using 6 illustrated facial expressions translated to a numeric rating on a scale of 0-10, with higher scores indicating worse pain). This scale has an established minimum clinically important difference (MCID) value of 1 face (2 points).¹¹ Per standard practice in equivalence trials, the equivalence margin was defined as half the MCID, with a value of 1.0 used in this study.

Secondary outcomes measured over the 6-week follow-up period included additional pain measurements using the Wong-Baker scale, measures of function and health-­related quality of life, analgesia use, days of absence from school or childcare, complication rates, and patient satisfaction. This study used modified intention-to-treat and per-protocol analyses.

The mean age of participants was 9.6 years; 39% were girls and 61% were boys. In the bandage group, 94% opted to have the soft bandage applied in the ED, and 95% of the rigid immobilization group were treated with a removable wrist splint in the ED. At 3 days, pain scores improved by 3.2 points (standard deviation [SD] = 2.1) in the soft bandage group and 3.1 points (SD = 2.1) in the rigid immobilization group. The adjusted difference was –0.1 (95% CI, –0.37 to 0.17) in the intention-to-treat analysis and –0.06 (95% CI, –0.34 to 0.21) in the per-protocol analysis, which were both less than the predetermined equivalence margin. This equivalence margin also was met at all secondary time points (1 day, 7 days, 3 weeks, and 6 weeks after treatment) and in subgroup analysis of those 4 to 7 years and 8 to 15 years.

Use of any analgesia in the prior 24 hours was slightly higher in the soft bandage group on Day 1 (83% vs 78%; P = .04) and Day 3 (57% vs 51%; P = .05), but this difference was not seen on Day 7. Satisfaction, measured via a 7-point Likert scale (range from “extremely satisfied” to “extremely unsatisfied”), was slightly lower in the soft bandage group on Day 1 (median 2 [interquartile range = 1, 2] vs median 1 [interquartile range = 1, 2]; P < .0001) but was not different after 6 weeks. There were no measured differences in any other secondary outcomes, including function, quality of life, and complication rates.

Continue to: By the primary end point...

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

By the primary end point of 3 days, 36 patients (7%) in the soft bandage group returned to medical care requesting a change to rigid immobilization, compared with 1 patient (0.2%) in the rigid immobilization group declining intervention.

WHAT’S NEW

Equivalence in pain and function scores

This trial showed equivalence in pain at 3 days’ follow-up in children with distal radius torus fractures who were offered bandaging and then immediately discharged from the ED, compared with rigid immobilization and clinical follow-up. There were no significant differences in pain or function between groups during the 6 weeks following the initial injury. De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of these fractures.

CAVEATS

Lack of masking likely introduced bias

There are no major caveats associated with managing distal radius torus fractures with a soft bandage and discharge from the ED, compared with the traditional treatment of rigid immobilization. However, bias was likely introduced in patient-reported outcomes due to the inability to mask patients and families to the treatment allocation. This may have led to overstating the severity of outcomes in the bandage group, given the strong preference for rigid immobilization, although equivalence was illustrated despite this potential bias.

CHALLENGES TO IMPLEMENTATION

Preferences may be difficult to change

Parents and clinicians demonstrated a preference for rigid immobilization, as shown in the imbalance in treatment crossovers, with 7% of children changing to the rigid immobilization group by the primary study end point of 3 days. The study authors hypothesized that crossovers may have been due to the perception by some parents that rigid immobilization is the gold standard of treatment, as well as clinicians’ seeking to escalate care for patients returning for follow-up. Policy and guideline changes, as well as physician efforts to educate patients on outcomes with soft bandage treatment, are likely to improve these misconceptions.

ILLUSTRATIVE CASE

A 9-year-old girl presents to your urgent care clinic after a fall while snowboarding for the first time. She reports falling forward onto her outstretched right hand and describes pain in her distal right forearm. She denies paresthesias, weakness, or lacerations. Physical examination reveals mild edema of the dorsal aspect of her distal right forearm and tenderness to palpation of the dorsal aspect of her distal radius. She denies tenderness to palpation of her ulna, anatomic snuffbox, hand, and elbow. Range of motion of the wrist is full on passive testing, but she declines active testing due to pain. Wrist radiographs reveal an uncomplicated torus fracture of the distal radius. Can immobilization with a soft bandage alone sufficiently treat this fracture?

Fractures of the distal radius are among the most common fractures of the upper extremity and commonly occur from a fall onto an outstretched hand.² In the pediatric population, torus fractures, also known as buckle fractures, are the most common type of distal radius fracture, comprising an estimated 50% of pediatric wrist fractures.^3,4 This is due to the presence of a physeal growth plate, thicker periosteum, and softer underlying bone in pediatric patients.^4,5 When an axial load is applied, as in a fall onto an outstretched hand, the force can lead to plastic deformation, with or without cortical disruption of the bone.^4,5

Pediatric torus fractures of the distal radius generally are treated with immobilization,² traditionally through a short arm cast or a removable, rigid wrist splint.^2,6 The wrist often is immobilized for 3 to 4 weeks, with routine follow-up and potential repeat plain film radiography to ensure stability.^2,6

Despite common use of immobilization, torus fractures of the distal radius are anatomically stable, and displacement is unlikely to occur.^7,8 As such, many studies have suggested that treatment of torus fractures with rigid immobilization in a cast or splint may not be necessary.^9,10 However, a 2018 Cochrane review concluded that the quality of evidence illustrating similar recovery between treatments was low, leaving uncertainty as to the most appropriate management strategy.⁶ Less casting and follow-up imaging could have positive implications for patient satisfaction, health care–associated costs, and radiation exposure.¹⁰

This study, the Forearm Fracture Recovery in Children Evaluation (FORCE) trial, compared the traditional treatment of distal radius torus fractures with rigid immobilization to soft immobilization and immediate discharge.

STUDY SUMMARY

Providing quality evidence for a standard of care

FORCE was a randomized controlled equivalence trial (N = 965) across 23 emergency departments (EDs) in the United Kingdom that compared pain and function in pediatric patients with distal radius torus fractures treated with a soft bandage and immediate discharge vs rigid immobilization and routine follow-up.¹ Patients included children ages 4 to 15 years presenting to the ED with a distal radius torus fracture, which was confirmed radiologically.

At 3 days, pain scores improved by 3.2 points in the soft bandage group and 3.1 points in the rigid immobilization group.

Patients with concomitant ipsilateral ulnar fractures were included in the study. Researchers excluded patients with injuries older than 36 hours, evidence of cortical disruption on radiograph (eg, greenstick fracture), or additional fractures other than the wrist, or those who were deemed unable to follow up with the full study protocol (eg, having insufficient English comprehension).

Continue to: Patients were randomly assigned...

Patients were randomly assigned in a 1:1 ratio to receive treatment with either a soft bandage such as a gauze roller bandage (n = 489) or rigid immobilization (n = 476). For patients in the bandage group, a soft bandage was applied in the ED or provided for home application without planned clinical follow-up. Patients in the rigid immobilization group were treated in the ED with either a removable manufactured splint or a molded splint or cast, followed by the standard follow-up practice of the treating center. Patients in the soft bandage group were advised not to wear the bandage for more than 3 weeks. Blinding was not possible, but the treatment team did not take part in patient follow-up.

The primary outcome was change in pain 3 days after treatment, measured on the Wong-Baker FACES Pain Rating Scale (an ordinal assessment using 6 illustrated facial expressions translated to a numeric rating on a scale of 0-10, with higher scores indicating worse pain). This scale has an established minimum clinically important difference (MCID) value of 1 face (2 points).¹¹ Per standard practice in equivalence trials, the equivalence margin was defined as half the MCID, with a value of 1.0 used in this study.

Secondary outcomes measured over the 6-week follow-up period included additional pain measurements using the Wong-Baker scale, measures of function and health-­related quality of life, analgesia use, days of absence from school or childcare, complication rates, and patient satisfaction. This study used modified intention-to-treat and per-protocol analyses.

The mean age of participants was 9.6 years; 39% were girls and 61% were boys. In the bandage group, 94% opted to have the soft bandage applied in the ED, and 95% of the rigid immobilization group were treated with a removable wrist splint in the ED. At 3 days, pain scores improved by 3.2 points (standard deviation [SD] = 2.1) in the soft bandage group and 3.1 points (SD = 2.1) in the rigid immobilization group. The adjusted difference was –0.1 (95% CI, –0.37 to 0.17) in the intention-to-treat analysis and –0.06 (95% CI, –0.34 to 0.21) in the per-protocol analysis, which were both less than the predetermined equivalence margin. This equivalence margin also was met at all secondary time points (1 day, 7 days, 3 weeks, and 6 weeks after treatment) and in subgroup analysis of those 4 to 7 years and 8 to 15 years.

Use of any analgesia in the prior 24 hours was slightly higher in the soft bandage group on Day 1 (83% vs 78%; P = .04) and Day 3 (57% vs 51%; P = .05), but this difference was not seen on Day 7. Satisfaction, measured via a 7-point Likert scale (range from “extremely satisfied” to “extremely unsatisfied”), was slightly lower in the soft bandage group on Day 1 (median 2 [interquartile range = 1, 2] vs median 1 [interquartile range = 1, 2]; P < .0001) but was not different after 6 weeks. There were no measured differences in any other secondary outcomes, including function, quality of life, and complication rates.

Continue to: By the primary end point...

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

By the primary end point of 3 days, 36 patients (7%) in the soft bandage group returned to medical care requesting a change to rigid immobilization, compared with 1 patient (0.2%) in the rigid immobilization group declining intervention.

WHAT’S NEW

Equivalence in pain and function scores

This trial showed equivalence in pain at 3 days’ follow-up in children with distal radius torus fractures who were offered bandaging and then immediately discharged from the ED, compared with rigid immobilization and clinical follow-up. There were no significant differences in pain or function between groups during the 6 weeks following the initial injury. De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of these fractures.

CAVEATS

Lack of masking likely introduced bias

There are no major caveats associated with managing distal radius torus fractures with a soft bandage and discharge from the ED, compared with the traditional treatment of rigid immobilization. However, bias was likely introduced in patient-reported outcomes due to the inability to mask patients and families to the treatment allocation. This may have led to overstating the severity of outcomes in the bandage group, given the strong preference for rigid immobilization, although equivalence was illustrated despite this potential bias.

CHALLENGES TO IMPLEMENTATION

Preferences may be difficult to change

Parents and clinicians demonstrated a preference for rigid immobilization, as shown in the imbalance in treatment crossovers, with 7% of children changing to the rigid immobilization group by the primary study end point of 3 days. The study authors hypothesized that crossovers may have been due to the perception by some parents that rigid immobilization is the gold standard of treatment, as well as clinicians’ seeking to escalate care for patients returning for follow-up. Policy and guideline changes, as well as physician efforts to educate patients on outcomes with soft bandage treatment, are likely to improve these misconceptions.

Managing first-time seizures and epilepsy often requires consultation with a neurologist or epileptologist for diagnosis and subsequent management, including when medical treatment fails or in determining whether patients may benefit from surgery. However, given the high prevalence of epilepsy and even higher incidence of a single seizure, family physicians contribute significantly to the management of these patients. The main issues are managing a first-time seizure, making the diagnosis, establishing a treatment plan, and exploring triggers and mitigating factors.

Seizure vs epilepsy

All patients with epilepsy experience seizures, but not every person who experiences a seizure has (or will develop) epilepsy. Nearly 10% of the population has one seizure during their lifetime,whereas the risk for epilepsy is just 3%.¹ Therefore, a first-time seizure may not herald epilepsy, defined as repetitive (≥ 2) unprovoked seizures more than 24 hours apart.² Seizures can be provoked (acute symptomatic) or unprovoked; a clear distinction between these 2 occurrences—as well as between single and recurrent seizures—is critical for proper management. A close look at the circumstances of a first-time seizure is imperative to define the nature of the event and the possibility of further seizures before devising a treatment plan.

Provoked seizures are due to an acute brain insult such as toxic-metabolic disorders, concussion, alcohol withdrawal, an adverse effect of a medication or its withdrawal, or photic stimulation presumably by disrupting the brain’s metabolic homeostasis or integrity. The key factor is that provoked seizures always happen in close temporal association with an acute insult. A single provoked seizure happens each year in 29 to 39 individuals per 100,000.³ While these seizures typically occur singly, there is a small risk they may recur if the triggering insult persists or repeats.¹ Therefore, more than 1 seizure per se may not indicate epilepsy.³

Unprovoked seizures reflect an underlying brain dysfunction. A single unprovoked seizure happens in 23 to 61 individuals per 100,000 per year, often in men in either younger or older age groups.³ Unprovoked seizures may occur only once or may recur (ie, evolve into epilepsy). The latter scenario happens in only about half of cases; the overall risk for a recurrent seizure within 2 years of a first seizure is estimated at 42% (24% to 65%, depending on the etiology and electroencephalogram [EEG] findings).⁴ More specifically, without treatment the relapse rate will be 36% at 1 year and 47% at 2 years.⁴ Further, a second unprovoked seizure, if untreated, would increase the risk for third and fourth seizures to 73% and 76%, respectively, within 4 years.³

Evaluating the first-time seizure

Ask the patient or observers about the circumstances of the event to differentiate provoked from unprovoked onset. For one thing, not all “spells” are seizures. The differential diagnoses may include syncope, psychogenic nonepileptic events, drug intoxication or withdrawal, migraine, panic attacks, sleep disorders (parasomnia), transient global amnesia, concussion, and transient ischemic attack. EEG, neuroimaging, and other relevant diagnostic tests often are needed (eg, electrocardiogram/echocardiogram/Holter monitoring to evaluate for syncope/cardiac arrhythmia). Clinically, syncopal episodes tend to be brief with rapid recovery and no confusion, speech problems, aura, or lateralizing signs such as hand posturing or lip smacking that are typical with focal seizures. However, cases of convulsive syncope can be challenging to assess without diagnostic tests.

Many patients have experienced prior undiagnosed seizures. Subtle prior events include episodes of deja vu, transient feelings of fear, unusual smells, and speech difficulties.

True convulsive seizures do not have the variability in clinical signs seen with psychogenic nonepileptic events (eg, alternating body parts involved or direction of movements). Transient global amnesia is a rare condition with no established diagnostic test and is considered a diagnosis of exclusion, although bitemporal hyperintensities on magnetic resonance imaging (MRI) may appear 12 to 48 hours after the clinical episode.⁵ Blood work is needed in patients with medical issues treated with multiple medications to evaluate for metabolic derangements; otherwise, routine blood work provides minimal information in stable patients.

Region-specific causes. Neurocysticercosis is common in some regions, such as Latin America; therefore, attention should be paid to this aspect of patient history.

Continue to: Is it really a first-time seizure?

Is it really a first-time seizure? A “first,” usually dramatic, generalized tonic-clonic seizure that triggers the diagnostic work-up may not be the very first seizure. Evidence suggests that many patients have experienced prior undiagnosed seizures. Subtle prior events often missed include episodes of deja vu, transient feelings of fear or unusual smells, speech difficulties, staring spells, or myoclonic jerks.¹ A routine EEG to record epileptiform discharges and a high-resolution brain MRI to rule out any intracranial pathology are indicated. However, if the EEG indicates a primary generalized (as opposed to focal-onset) epilepsy, a brain MRI may not be needed. If a routine EEG is unrevealing, long-term video-EEG monitoring may be needed to detect an abnormality.

Accuracy of EEG and MRI. Following a first unprovoked seizure, routine EEG to detect epileptiform discharges in adults has yielded a sensitivity of 17.3% and specificity of 94.7%. In evaluating children, these values are 57.8% and 69.6%, respectively.⁶ If results are equivocal, a 24-hour EEG can increase the likelihood of detecting epileptiform discharges to 89% of patients.⁷ Brain MRI may detect an abnormality in 12% to 14% of patients with newly diagnosed epilepsy, and in up to 80% of those with recurrent seizures.⁸ In confirming hippocampus sclerosis, MRI has demonstrated a sensitivity of 93% and specificity of 86%.⁹

When to treat a first-time seizure. Available data and prediction models identify risk factors that would help determine whether to start an antiseizure medication after a first unprovoked seizure: abnormal EEG with particular epileptiform activity, abnormal neurologic exam, abnormal computerized tomography or MRI results, nocturnal seizure, focal seizure, or family history of seizures. In the absence of such risk factors, chances of further unprovoked seizures are not high enough to justify treatment with antiseizure medications. However, if a second unprovoked seizure were to occur, that would meet the definition of epilepsy, and treatment is indicated due to the high risk for further seizures.^10,11

Epilepsy diagnosis

The International League Against Epilepsy (ILAE) previously defined epilepsy as 2 unprovoked seizures more than 24 hours apart. However, a more recent ILAE task force modified this definition: even a single unprovoked seizure would be enough to diagnose epilepsy if there is high probability of further seizures—eg, in the presence of definitive epileptiform discharges on EEG or presence of a brain tumor or a remote brain insult on imaging, since such conditions induce an enduring predisposition to generate epileptic seizures. ² Also, a single unprovoked seizure is enough to diagnose epilepsy if it is part of an epileptic syndrome such as juvenile myoclonic epilepsy. Further, a time limit was added to the definition—ie, epilepsy is considered resolved if a patient remains seizure free for 10 years without use of antiseizure medications during the past 5 years. However, given the multitude of variables and evidence, the task force acknowledged the need for individualized considerations. ²

Seizure classification

Classification of seizure type is based on the site of seizure onset and its spread pattern—ie, focal, generalized, or unknown onset.

Continue to: Focal-onset seizures

Focal-onset seizures originate “within networks limited to one hemisphere,” although possibly in more than 1 region (ie, multifocal, and presence or absence of loss of awareness). ¹² Focal seizures may then be further classified into “motor onset” or “nonmotor onset” (eg, autonomic, emotional, sensory). ²

Generalized seizures are those “originating at some point within, and rapidly engaging, bilaterally distributed networks.” ¹³ Unlike focal-onset seizures, generalized seizures are not classified based on awareness, as most generalized seizures involve loss of awareness (absence) or total loss of consciousness (generalized tonic-clonic). They are instead categorized based on the presence of motor vs nonmotor features (eg, tonic-clonic, myoclonic, atonic). Epilepsy classification is quite dynamic and constantly updated based on new genetic, electroencephalographic, and neuroimaging discoveries.

Treatment of epilepsy

Antiseizure medications

Treatment with antiseizure medications (ASMs; formerly known as antiepileptic drugs ) is the mainstay of epilepsy management. Achieving efficacy (seizure freedom) and tolerability (minimal adverse effects) are the primary goals of treatment. Factors that should govern the selection of an ASM include the seizure type/epilepsy syndrome, adverse effect profile of the ASM, pharmacodynamic/pharmacokinetic considerations, and patient comorbidities.

Levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies.

The Standard and New Antiepileptic Drugs (SANAD I and II) trials provide data from direct, unblinded, and longitudinal comparisons of existing and new ASMs and their utility in different seizure types. In the SANAD I cohort of patients with generalized and unclassified epilepsies, valproate was superior to lamotrigine and topiramate for 12-month remission and treatment failure rates, respectively.¹⁴ However, valproate generally is avoided in women of childbearing age due its potential adverse effects during pregnancy. In focal epilepsies, lamotrigine was superior to carbamazepine, gabapentin, and topiramate with respect to treatment failure, and noninferior to carbamazepine for 12-month remission.¹⁵ In the SANAD II trial, levetiracetam was noninferior to valproate for incidence of adverse events in patients with generalized and unclassified epilepsies although was found to be neither more clinically effective nor more cost effective.¹⁶ For patients of childbearing potential with generalized and unclassified epilepsies, there is evidence to support the safe and effective use of levetiracetam.¹⁷In focal epilepsies, lamotrigine was superior to levetiracetam and zonisamide with respect to treatment failures and adverse events and was noninferior to zonisamide for 12-month remission.¹⁸ In summary, levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies while lamotrigine is deemed an appropriate first-line agent for focal epilepsies (TABLE 1^19-28).

Drug level monitoring. It is standard practice to periodically monitor serum levels in patients taking first-generation ASMs such as phenytoin, carbamazepine, phenobarbital, and valproic acid because of their narrow therapeutic range and the potential for overdose or interaction with other medications or foods (eg, grapefruit juice may increase carbamazepine serum level by inhibiting ­CYP3A4, the enzyme that metabolizes the drug). Patients taking newer ASMs may not require regular serum level monitoring except during titration, with hepatic or renal dosing, when concomitantly used with estrogen-based oral contraceptives (eg, lamotrigine), before or during pregnancy, or when nonadherence is suspected.

Continue to: Can antiseizure treatment be stopped?

Can antiseizure treatment be stopped?

Current evidence favors continuing ASM therapy in patients whose seizures are under control, although the decision should be tailored to an individual’s circumstances. According to the 2021 American Academy of Neurology (AAN) guidelines, adults who have been seizure free for at least 2 years and discontinue ASMs are possibly still at higher risk for seizure recurrence in the long term (24-60 months), compared with those who continue treatment.²⁹ On the other hand, for adults who have been seizure free for at least 12 months, ASM withdrawal may not increase their risk for status epilepticus, and there are insufficient data to support or refute an effect on mortality or quality of life with ASM withdrawal in this population. The decision to taper or maintain ASM therapy in seizure-free patients also should take into consideration other clinically relevant outcome measures such as the patient’s lifestyle and medication adverse effects. Therefore, this decision should be made after sufficient discussion with patients and their caregivers. (Information for patients can be found at: www.epilepsy.com/treatment/medicines/stopping-medication.)

There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

For children, the AAN guideline panel recommends discussing with family the small risk (2%) for becoming medication resistant if seizures recur during or after ASM withdrawal. ²⁹ For children who have been seizure free for 18 to 24 months, there is probably not a significant long-term (24-48 months) difference in seizure recurrence in those who taper ASMs vs those who do not. However, presence of epileptiform discharges on EEG before discontinuation of an ASM indicates increased risk for seizure recurrence. ²⁹

Intractable (refractory) epilepsy

While most patients with epilepsy attain complete seizure control with appropriate drug therapy, approximately 30% continue to experience seizures (“drug-resistant” epilepsy, also termed intractable or refractory ). ³⁰ In 2010, the ILAE defined drug-resistant epilepsy as “failure of adequate trials of two tolerated, appropriately chosen and used anti-epileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom” (defined as cessation of seizures for at least 3 times the longest pre-intervention inter-seizure interval or 12 months, whichever is longer). ^21,31 It should be noted that drug withdrawal due to adverse effects is not counted as failure of that ASM. Recognition of drug-resistant epilepsy may prompt referral to an epileptologist who can consider rational combination drug therapy or surgical resection of the seizure focus, vagus nerve stimulation, electrical stimulation of the seizure focus, or deep brain (thalamic) stimulation.

Seizure triggers and mitigating factors

Epilepsy mostly affects patients during seizure episodes; however, the unpredictability of these events adds significantly to the burden of disease. There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

Noncompliance with antiseizure medications is a common seizure trigger affecting up to one-half of patients with epilepsy.³²

Continue to: Medications

Medications may provoke seizures in susceptible individuals (TABLE 2^33-35).

Sleep deprivation is a potential seizure trigger in people with epilepsy based on observational studies, case reports, patient surveys, and EEG-based studies, although data from randomized controlled studies are limited.³⁶ The standard best practice is to encourage appropriate sleep hygiene, which involves getting at least 7 hours of sleep per night.³⁷

Alcohol is a GABAergic substance like benzodiazepines with antiseizure effects. However, it acts as a potential precipitant of seizures in cases of withdrawal or acute intoxication, or when it leads to sleep disruption or nonadherence to antiseizure medications. Therefore, advise patients with alcohol use disorder to slowly taper consumption (best done through a support program) and avoid sudden withdrawal. However, complete abstinence from alcohol use is not often recommended except in special circumstances (eg, a history of alcohol-related seizures). Several studies have demonstrated that modest alcohol use (1-2 drinks per occasion) does not increase seizure frequency or significantly alter serum concentrations of commonly used ASMs.³⁸

Cannabis and other substances. The 2 main biologically active components of marijuana are delta-9-tetrahydrocannibinol (THC), the main psychoactive constituent, and cannabidiol (CBD). Animal and human studies have demonstrated anticonvulsant properties of THC and CBD. But THC, in high amounts, can result in adverse cognitive effects and worsening seizures.³⁹ A purified 98% oil-based CBD extract (Epidiolex) has been approved as an adjunctive treatment for certain medically refractory epilepsy syndromes in children and young adults—ie, Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex syndrome.⁴⁰ There are no reliable data on the effect of recreational use of marijuana on seizure control. Other illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

Special clinical cases

Pregnancy and epilepsy

Despite the potential adverse effects of ASMs on fetal health, the current global consensus is to continue treatment during pregnancy, given that the potential harm of convulsive seizures outweighs the potential risks associated with in-utero exposure to ASMs. There is not enough evidence to indicate significant harm to the fetus caused by focal, absence, or myoclonic seizures. Low-dose folic acid is used to minimize the risks of ASMs during pregnancy.

Continue to: As the fetus develops...

Illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

As the fetus develops, there are changes in volume of ASM distribution, renal clearance, protein binding, and hepatic metabolism, which require checking serum levels at regular intervals and making dosage adjustments.

The ongoing study evaluating Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)⁴¹ has led to multiple landmark studies guiding the choice of preferred ASMs during pregnancy in patients with epilepsy.^42,43 This has culminated in today’s use of lamotrigine and levetiracetam as the 2 preferred agents (while avoiding valproate) in pregnant patients with epilepsy.⁴⁴

Psychogenic nonepileptic seizures

Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers.

A form of conversion disorder, psychogenic nonepileptic seizures (PNES) manifests as abnormal motor or behavioral events mimicking seizures but without associated epileptiform discharges on EEG. This is observed in 10% of patients seen in epilepsy clinics and even more often in those admitted to epilepsy­ monitoring units (25%-40%).⁴⁵ Diagnosis of PNES requires EEG monitoring both for confirmation and for discernment from true epileptic seizures, in particular frontal lobe epilepsy that may clinically mimic PNES. PNES often is associated with underlying psychological tensions or comorbid conditions such as depression, anxiety, or traumatic life experiences. There is no treatment for PNES per se, and its management is focused on controlling any underlying psychological comorbidities that may not always be obvious. There is some evidence suggesting that these patients experience an innate inability to verbally express their emotions and instead subconsciously resort to psychosomatics to express them in a somatic dimension.^46,47

Status epilepticus

Defined as prolonged seizures (> 5 min) or 2 consecutive seizures without regaining aware ness in between, status epilepticus (SE) is a potentially fatal condition. Subclinical nonconvulsive SE, especially in comatose patients, can be diagnosed only via EEG monitoring. Untreated SE may manifest as a diagnostic dilemma in unresponsive or critically ill patients and can increase the risk for mortality. ⁴⁸

Febrile seizures

Febrile seizures affect 2% to 5% of children most often in the second year of life.⁴⁹ The use of preventive antiseizure medication is not recommended; instead, the key is to investigate the underlying febrile illness. Lumbar puncture is indicated if there are signs and symptoms of meningitis (25% of children with bacterial meningitis present with seizures).⁴⁹ Febrile seizures often are self-limited, but there is risk for SE in up to 15% of cases.⁵⁰ If convulsive febrile seizures last longer than 5 minutes, initiate benzodiazepines followed by the standard protocol used for the management of SE.⁵¹

Continue to: Epilepsy as a spectrum disorder

The higher prevalence of comorbid cognitive and psychiatric conditions in patients with epilepsy, affecting about half of patients, ⁵² suggests that seizures may constitute only one aspect of a multifaceted disease that otherwise should be considered a spectrum disorder. Among such conditions are memory deficits, depression, and anxiety. Conversely, epilepsy is more common in patients with depression than in those without. ⁵²

Social impact of epilepsy

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

Vehicle driving regulations. Patients with epilepsy are required to follow state law regarding driving restrictions. Different states have different rules and regulations about driving restrictions and reporting requirements (by patients or their physicians). Refer patients to the Department of Motor Vehicles (DMV) in their state of residence for up-to-date instructions.⁵³ The Epilepsy Foundation (epilepsy.com) can serve as a resource for each state’s DMV website.

Employment assistance. Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers. The Americans with Disabilities Act (ADA) and the US Equal Employment Opportunity Commission (EEOC) forbid discrimination against qualified people with disabilities, including those with epilepsy, and require reasonable accommodations in the workplace (www.eeoc.gov/laws/guidance/­epilepsy-workplace-and-ada).⁵⁴

CORRESPONDENCE
Gholam K. Motamedi, MD, Department of Neurology, PHC 7, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007; [email protected]

Managing first-time seizures and epilepsy often requires consultation with a neurologist or epileptologist for diagnosis and subsequent management, including when medical treatment fails or in determining whether patients may benefit from surgery. However, given the high prevalence of epilepsy and even higher incidence of a single seizure, family physicians contribute significantly to the management of these patients. The main issues are managing a first-time seizure, making the diagnosis, establishing a treatment plan, and exploring triggers and mitigating factors.

Seizure vs epilepsy

All patients with epilepsy experience seizures, but not every person who experiences a seizure has (or will develop) epilepsy. Nearly 10% of the population has one seizure during their lifetime,whereas the risk for epilepsy is just 3%.¹ Therefore, a first-time seizure may not herald epilepsy, defined as repetitive (≥ 2) unprovoked seizures more than 24 hours apart.² Seizures can be provoked (acute symptomatic) or unprovoked; a clear distinction between these 2 occurrences—as well as between single and recurrent seizures—is critical for proper management. A close look at the circumstances of a first-time seizure is imperative to define the nature of the event and the possibility of further seizures before devising a treatment plan.

Provoked seizures are due to an acute brain insult such as toxic-metabolic disorders, concussion, alcohol withdrawal, an adverse effect of a medication or its withdrawal, or photic stimulation presumably by disrupting the brain’s metabolic homeostasis or integrity. The key factor is that provoked seizures always happen in close temporal association with an acute insult. A single provoked seizure happens each year in 29 to 39 individuals per 100,000.³ While these seizures typically occur singly, there is a small risk they may recur if the triggering insult persists or repeats.¹ Therefore, more than 1 seizure per se may not indicate epilepsy.³

Unprovoked seizures reflect an underlying brain dysfunction. A single unprovoked seizure happens in 23 to 61 individuals per 100,000 per year, often in men in either younger or older age groups.³ Unprovoked seizures may occur only once or may recur (ie, evolve into epilepsy). The latter scenario happens in only about half of cases; the overall risk for a recurrent seizure within 2 years of a first seizure is estimated at 42% (24% to 65%, depending on the etiology and electroencephalogram [EEG] findings).⁴ More specifically, without treatment the relapse rate will be 36% at 1 year and 47% at 2 years.⁴ Further, a second unprovoked seizure, if untreated, would increase the risk for third and fourth seizures to 73% and 76%, respectively, within 4 years.³

Evaluating the first-time seizure

Ask the patient or observers about the circumstances of the event to differentiate provoked from unprovoked onset. For one thing, not all “spells” are seizures. The differential diagnoses may include syncope, psychogenic nonepileptic events, drug intoxication or withdrawal, migraine, panic attacks, sleep disorders (parasomnia), transient global amnesia, concussion, and transient ischemic attack. EEG, neuroimaging, and other relevant diagnostic tests often are needed (eg, electrocardiogram/echocardiogram/Holter monitoring to evaluate for syncope/cardiac arrhythmia). Clinically, syncopal episodes tend to be brief with rapid recovery and no confusion, speech problems, aura, or lateralizing signs such as hand posturing or lip smacking that are typical with focal seizures. However, cases of convulsive syncope can be challenging to assess without diagnostic tests.

Many patients have experienced prior undiagnosed seizures. Subtle prior events include episodes of deja vu, transient feelings of fear, unusual smells, and speech difficulties.

True convulsive seizures do not have the variability in clinical signs seen with psychogenic nonepileptic events (eg, alternating body parts involved or direction of movements). Transient global amnesia is a rare condition with no established diagnostic test and is considered a diagnosis of exclusion, although bitemporal hyperintensities on magnetic resonance imaging (MRI) may appear 12 to 48 hours after the clinical episode.⁵ Blood work is needed in patients with medical issues treated with multiple medications to evaluate for metabolic derangements; otherwise, routine blood work provides minimal information in stable patients.

Region-specific causes. Neurocysticercosis is common in some regions, such as Latin America; therefore, attention should be paid to this aspect of patient history.

Continue to: Is it really a first-time seizure?

Is it really a first-time seizure? A “first,” usually dramatic, generalized tonic-clonic seizure that triggers the diagnostic work-up may not be the very first seizure. Evidence suggests that many patients have experienced prior undiagnosed seizures. Subtle prior events often missed include episodes of deja vu, transient feelings of fear or unusual smells, speech difficulties, staring spells, or myoclonic jerks.¹ A routine EEG to record epileptiform discharges and a high-resolution brain MRI to rule out any intracranial pathology are indicated. However, if the EEG indicates a primary generalized (as opposed to focal-onset) epilepsy, a brain MRI may not be needed. If a routine EEG is unrevealing, long-term video-EEG monitoring may be needed to detect an abnormality.

Accuracy of EEG and MRI. Following a first unprovoked seizure, routine EEG to detect epileptiform discharges in adults has yielded a sensitivity of 17.3% and specificity of 94.7%. In evaluating children, these values are 57.8% and 69.6%, respectively.⁶ If results are equivocal, a 24-hour EEG can increase the likelihood of detecting epileptiform discharges to 89% of patients.⁷ Brain MRI may detect an abnormality in 12% to 14% of patients with newly diagnosed epilepsy, and in up to 80% of those with recurrent seizures.⁸ In confirming hippocampus sclerosis, MRI has demonstrated a sensitivity of 93% and specificity of 86%.⁹

When to treat a first-time seizure. Available data and prediction models identify risk factors that would help determine whether to start an antiseizure medication after a first unprovoked seizure: abnormal EEG with particular epileptiform activity, abnormal neurologic exam, abnormal computerized tomography or MRI results, nocturnal seizure, focal seizure, or family history of seizures. In the absence of such risk factors, chances of further unprovoked seizures are not high enough to justify treatment with antiseizure medications. However, if a second unprovoked seizure were to occur, that would meet the definition of epilepsy, and treatment is indicated due to the high risk for further seizures.^10,11

Epilepsy diagnosis

The International League Against Epilepsy (ILAE) previously defined epilepsy as 2 unprovoked seizures more than 24 hours apart. However, a more recent ILAE task force modified this definition: even a single unprovoked seizure would be enough to diagnose epilepsy if there is high probability of further seizures—eg, in the presence of definitive epileptiform discharges on EEG or presence of a brain tumor or a remote brain insult on imaging, since such conditions induce an enduring predisposition to generate epileptic seizures. ² Also, a single unprovoked seizure is enough to diagnose epilepsy if it is part of an epileptic syndrome such as juvenile myoclonic epilepsy. Further, a time limit was added to the definition—ie, epilepsy is considered resolved if a patient remains seizure free for 10 years without use of antiseizure medications during the past 5 years. However, given the multitude of variables and evidence, the task force acknowledged the need for individualized considerations. ²

Seizure classification

Classification of seizure type is based on the site of seizure onset and its spread pattern—ie, focal, generalized, or unknown onset.

Continue to: Focal-onset seizures

Focal-onset seizures originate “within networks limited to one hemisphere,” although possibly in more than 1 region (ie, multifocal, and presence or absence of loss of awareness). ¹² Focal seizures may then be further classified into “motor onset” or “nonmotor onset” (eg, autonomic, emotional, sensory). ²

Generalized seizures are those “originating at some point within, and rapidly engaging, bilaterally distributed networks.” ¹³ Unlike focal-onset seizures, generalized seizures are not classified based on awareness, as most generalized seizures involve loss of awareness (absence) or total loss of consciousness (generalized tonic-clonic). They are instead categorized based on the presence of motor vs nonmotor features (eg, tonic-clonic, myoclonic, atonic). Epilepsy classification is quite dynamic and constantly updated based on new genetic, electroencephalographic, and neuroimaging discoveries.

Treatment of epilepsy

Antiseizure medications

Treatment with antiseizure medications (ASMs; formerly known as antiepileptic drugs ) is the mainstay of epilepsy management. Achieving efficacy (seizure freedom) and tolerability (minimal adverse effects) are the primary goals of treatment. Factors that should govern the selection of an ASM include the seizure type/epilepsy syndrome, adverse effect profile of the ASM, pharmacodynamic/pharmacokinetic considerations, and patient comorbidities.

Levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies.

The Standard and New Antiepileptic Drugs (SANAD I and II) trials provide data from direct, unblinded, and longitudinal comparisons of existing and new ASMs and their utility in different seizure types. In the SANAD I cohort of patients with generalized and unclassified epilepsies, valproate was superior to lamotrigine and topiramate for 12-month remission and treatment failure rates, respectively.¹⁴ However, valproate generally is avoided in women of childbearing age due its potential adverse effects during pregnancy. In focal epilepsies, lamotrigine was superior to carbamazepine, gabapentin, and topiramate with respect to treatment failure, and noninferior to carbamazepine for 12-month remission.¹⁵ In the SANAD II trial, levetiracetam was noninferior to valproate for incidence of adverse events in patients with generalized and unclassified epilepsies although was found to be neither more clinically effective nor more cost effective.¹⁶ For patients of childbearing potential with generalized and unclassified epilepsies, there is evidence to support the safe and effective use of levetiracetam.¹⁷In focal epilepsies, lamotrigine was superior to levetiracetam and zonisamide with respect to treatment failures and adverse events and was noninferior to zonisamide for 12-month remission.¹⁸ In summary, levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies while lamotrigine is deemed an appropriate first-line agent for focal epilepsies (TABLE 1^19-28).

Drug level monitoring. It is standard practice to periodically monitor serum levels in patients taking first-generation ASMs such as phenytoin, carbamazepine, phenobarbital, and valproic acid because of their narrow therapeutic range and the potential for overdose or interaction with other medications or foods (eg, grapefruit juice may increase carbamazepine serum level by inhibiting ­CYP3A4, the enzyme that metabolizes the drug). Patients taking newer ASMs may not require regular serum level monitoring except during titration, with hepatic or renal dosing, when concomitantly used with estrogen-based oral contraceptives (eg, lamotrigine), before or during pregnancy, or when nonadherence is suspected.

Continue to: Can antiseizure treatment be stopped?

Can antiseizure treatment be stopped?

Current evidence favors continuing ASM therapy in patients whose seizures are under control, although the decision should be tailored to an individual’s circumstances. According to the 2021 American Academy of Neurology (AAN) guidelines, adults who have been seizure free for at least 2 years and discontinue ASMs are possibly still at higher risk for seizure recurrence in the long term (24-60 months), compared with those who continue treatment.²⁹ On the other hand, for adults who have been seizure free for at least 12 months, ASM withdrawal may not increase their risk for status epilepticus, and there are insufficient data to support or refute an effect on mortality or quality of life with ASM withdrawal in this population. The decision to taper or maintain ASM therapy in seizure-free patients also should take into consideration other clinically relevant outcome measures such as the patient’s lifestyle and medication adverse effects. Therefore, this decision should be made after sufficient discussion with patients and their caregivers. (Information for patients can be found at: www.epilepsy.com/treatment/medicines/stopping-medication.)

There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

For children, the AAN guideline panel recommends discussing with family the small risk (2%) for becoming medication resistant if seizures recur during or after ASM withdrawal. ²⁹ For children who have been seizure free for 18 to 24 months, there is probably not a significant long-term (24-48 months) difference in seizure recurrence in those who taper ASMs vs those who do not. However, presence of epileptiform discharges on EEG before discontinuation of an ASM indicates increased risk for seizure recurrence. ²⁹

Intractable (refractory) epilepsy

While most patients with epilepsy attain complete seizure control with appropriate drug therapy, approximately 30% continue to experience seizures (“drug-resistant” epilepsy, also termed intractable or refractory ). ³⁰ In 2010, the ILAE defined drug-resistant epilepsy as “failure of adequate trials of two tolerated, appropriately chosen and used anti-epileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom” (defined as cessation of seizures for at least 3 times the longest pre-intervention inter-seizure interval or 12 months, whichever is longer). ^21,31 It should be noted that drug withdrawal due to adverse effects is not counted as failure of that ASM. Recognition of drug-resistant epilepsy may prompt referral to an epileptologist who can consider rational combination drug therapy or surgical resection of the seizure focus, vagus nerve stimulation, electrical stimulation of the seizure focus, or deep brain (thalamic) stimulation.

Seizure triggers and mitigating factors

Epilepsy mostly affects patients during seizure episodes; however, the unpredictability of these events adds significantly to the burden of disease. There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

Noncompliance with antiseizure medications is a common seizure trigger affecting up to one-half of patients with epilepsy.³²

Continue to: Medications

Medications may provoke seizures in susceptible individuals (TABLE 2^33-35).

Sleep deprivation is a potential seizure trigger in people with epilepsy based on observational studies, case reports, patient surveys, and EEG-based studies, although data from randomized controlled studies are limited.³⁶ The standard best practice is to encourage appropriate sleep hygiene, which involves getting at least 7 hours of sleep per night.³⁷

Alcohol is a GABAergic substance like benzodiazepines with antiseizure effects. However, it acts as a potential precipitant of seizures in cases of withdrawal or acute intoxication, or when it leads to sleep disruption or nonadherence to antiseizure medications. Therefore, advise patients with alcohol use disorder to slowly taper consumption (best done through a support program) and avoid sudden withdrawal. However, complete abstinence from alcohol use is not often recommended except in special circumstances (eg, a history of alcohol-related seizures). Several studies have demonstrated that modest alcohol use (1-2 drinks per occasion) does not increase seizure frequency or significantly alter serum concentrations of commonly used ASMs.³⁸

Cannabis and other substances. The 2 main biologically active components of marijuana are delta-9-tetrahydrocannibinol (THC), the main psychoactive constituent, and cannabidiol (CBD). Animal and human studies have demonstrated anticonvulsant properties of THC and CBD. But THC, in high amounts, can result in adverse cognitive effects and worsening seizures.³⁹ A purified 98% oil-based CBD extract (Epidiolex) has been approved as an adjunctive treatment for certain medically refractory epilepsy syndromes in children and young adults—ie, Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex syndrome.⁴⁰ There are no reliable data on the effect of recreational use of marijuana on seizure control. Other illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

Special clinical cases

Pregnancy and epilepsy

Despite the potential adverse effects of ASMs on fetal health, the current global consensus is to continue treatment during pregnancy, given that the potential harm of convulsive seizures outweighs the potential risks associated with in-utero exposure to ASMs. There is not enough evidence to indicate significant harm to the fetus caused by focal, absence, or myoclonic seizures. Low-dose folic acid is used to minimize the risks of ASMs during pregnancy.

Continue to: As the fetus develops...

Illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

As the fetus develops, there are changes in volume of ASM distribution, renal clearance, protein binding, and hepatic metabolism, which require checking serum levels at regular intervals and making dosage adjustments.

The ongoing study evaluating Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)⁴¹ has led to multiple landmark studies guiding the choice of preferred ASMs during pregnancy in patients with epilepsy.^42,43 This has culminated in today’s use of lamotrigine and levetiracetam as the 2 preferred agents (while avoiding valproate) in pregnant patients with epilepsy.⁴⁴

Psychogenic nonepileptic seizures

Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers.

A form of conversion disorder, psychogenic nonepileptic seizures (PNES) manifests as abnormal motor or behavioral events mimicking seizures but without associated epileptiform discharges on EEG. This is observed in 10% of patients seen in epilepsy clinics and even more often in those admitted to epilepsy­ monitoring units (25%-40%).⁴⁵ Diagnosis of PNES requires EEG monitoring both for confirmation and for discernment from true epileptic seizures, in particular frontal lobe epilepsy that may clinically mimic PNES. PNES often is associated with underlying psychological tensions or comorbid conditions such as depression, anxiety, or traumatic life experiences. There is no treatment for PNES per se, and its management is focused on controlling any underlying psychological comorbidities that may not always be obvious. There is some evidence suggesting that these patients experience an innate inability to verbally express their emotions and instead subconsciously resort to psychosomatics to express them in a somatic dimension.^46,47

Status epilepticus

Defined as prolonged seizures (> 5 min) or 2 consecutive seizures without regaining aware ness in between, status epilepticus (SE) is a potentially fatal condition. Subclinical nonconvulsive SE, especially in comatose patients, can be diagnosed only via EEG monitoring. Untreated SE may manifest as a diagnostic dilemma in unresponsive or critically ill patients and can increase the risk for mortality. ⁴⁸

Febrile seizures

Febrile seizures affect 2% to 5% of children most often in the second year of life.⁴⁹ The use of preventive antiseizure medication is not recommended; instead, the key is to investigate the underlying febrile illness. Lumbar puncture is indicated if there are signs and symptoms of meningitis (25% of children with bacterial meningitis present with seizures).⁴⁹ Febrile seizures often are self-limited, but there is risk for SE in up to 15% of cases.⁵⁰ If convulsive febrile seizures last longer than 5 minutes, initiate benzodiazepines followed by the standard protocol used for the management of SE.⁵¹

Continue to: Epilepsy as a spectrum disorder

The higher prevalence of comorbid cognitive and psychiatric conditions in patients with epilepsy, affecting about half of patients, ⁵² suggests that seizures may constitute only one aspect of a multifaceted disease that otherwise should be considered a spectrum disorder. Among such conditions are memory deficits, depression, and anxiety. Conversely, epilepsy is more common in patients with depression than in those without. ⁵²

Social impact of epilepsy

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

Vehicle driving regulations. Patients with epilepsy are required to follow state law regarding driving restrictions. Different states have different rules and regulations about driving restrictions and reporting requirements (by patients or their physicians). Refer patients to the Department of Motor Vehicles (DMV) in their state of residence for up-to-date instructions.⁵³ The Epilepsy Foundation (epilepsy.com) can serve as a resource for each state’s DMV website.

Employment assistance. Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers. The Americans with Disabilities Act (ADA) and the US Equal Employment Opportunity Commission (EEOC) forbid discrimination against qualified people with disabilities, including those with epilepsy, and require reasonable accommodations in the workplace (www.eeoc.gov/laws/guidance/­epilepsy-workplace-and-ada).⁵⁴

CORRESPONDENCE
Gholam K. Motamedi, MD, Department of Neurology, PHC 7, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007; [email protected]

Managing first-time seizures and epilepsy often requires consultation with a neurologist or epileptologist for diagnosis and subsequent management, including when medical treatment fails or in determining whether patients may benefit from surgery. However, given the high prevalence of epilepsy and even higher incidence of a single seizure, family physicians contribute significantly to the management of these patients. The main issues are managing a first-time seizure, making the diagnosis, establishing a treatment plan, and exploring triggers and mitigating factors.

Seizure vs epilepsy

All patients with epilepsy experience seizures, but not every person who experiences a seizure has (or will develop) epilepsy. Nearly 10% of the population has one seizure during their lifetime,whereas the risk for epilepsy is just 3%.¹ Therefore, a first-time seizure may not herald epilepsy, defined as repetitive (≥ 2) unprovoked seizures more than 24 hours apart.² Seizures can be provoked (acute symptomatic) or unprovoked; a clear distinction between these 2 occurrences—as well as between single and recurrent seizures—is critical for proper management. A close look at the circumstances of a first-time seizure is imperative to define the nature of the event and the possibility of further seizures before devising a treatment plan.

Provoked seizures are due to an acute brain insult such as toxic-metabolic disorders, concussion, alcohol withdrawal, an adverse effect of a medication or its withdrawal, or photic stimulation presumably by disrupting the brain’s metabolic homeostasis or integrity. The key factor is that provoked seizures always happen in close temporal association with an acute insult. A single provoked seizure happens each year in 29 to 39 individuals per 100,000.³ While these seizures typically occur singly, there is a small risk they may recur if the triggering insult persists or repeats.¹ Therefore, more than 1 seizure per se may not indicate epilepsy.³

Unprovoked seizures reflect an underlying brain dysfunction. A single unprovoked seizure happens in 23 to 61 individuals per 100,000 per year, often in men in either younger or older age groups.³ Unprovoked seizures may occur only once or may recur (ie, evolve into epilepsy). The latter scenario happens in only about half of cases; the overall risk for a recurrent seizure within 2 years of a first seizure is estimated at 42% (24% to 65%, depending on the etiology and electroencephalogram [EEG] findings).⁴ More specifically, without treatment the relapse rate will be 36% at 1 year and 47% at 2 years.⁴ Further, a second unprovoked seizure, if untreated, would increase the risk for third and fourth seizures to 73% and 76%, respectively, within 4 years.³

Evaluating the first-time seizure

Ask the patient or observers about the circumstances of the event to differentiate provoked from unprovoked onset. For one thing, not all “spells” are seizures. The differential diagnoses may include syncope, psychogenic nonepileptic events, drug intoxication or withdrawal, migraine, panic attacks, sleep disorders (parasomnia), transient global amnesia, concussion, and transient ischemic attack. EEG, neuroimaging, and other relevant diagnostic tests often are needed (eg, electrocardiogram/echocardiogram/Holter monitoring to evaluate for syncope/cardiac arrhythmia). Clinically, syncopal episodes tend to be brief with rapid recovery and no confusion, speech problems, aura, or lateralizing signs such as hand posturing or lip smacking that are typical with focal seizures. However, cases of convulsive syncope can be challenging to assess without diagnostic tests.

Many patients have experienced prior undiagnosed seizures. Subtle prior events include episodes of deja vu, transient feelings of fear, unusual smells, and speech difficulties.

True convulsive seizures do not have the variability in clinical signs seen with psychogenic nonepileptic events (eg, alternating body parts involved or direction of movements). Transient global amnesia is a rare condition with no established diagnostic test and is considered a diagnosis of exclusion, although bitemporal hyperintensities on magnetic resonance imaging (MRI) may appear 12 to 48 hours after the clinical episode.⁵ Blood work is needed in patients with medical issues treated with multiple medications to evaluate for metabolic derangements; otherwise, routine blood work provides minimal information in stable patients.

Region-specific causes. Neurocysticercosis is common in some regions, such as Latin America; therefore, attention should be paid to this aspect of patient history.

Continue to: Is it really a first-time seizure?

Is it really a first-time seizure? A “first,” usually dramatic, generalized tonic-clonic seizure that triggers the diagnostic work-up may not be the very first seizure. Evidence suggests that many patients have experienced prior undiagnosed seizures. Subtle prior events often missed include episodes of deja vu, transient feelings of fear or unusual smells, speech difficulties, staring spells, or myoclonic jerks.¹ A routine EEG to record epileptiform discharges and a high-resolution brain MRI to rule out any intracranial pathology are indicated. However, if the EEG indicates a primary generalized (as opposed to focal-onset) epilepsy, a brain MRI may not be needed. If a routine EEG is unrevealing, long-term video-EEG monitoring may be needed to detect an abnormality.

Accuracy of EEG and MRI. Following a first unprovoked seizure, routine EEG to detect epileptiform discharges in adults has yielded a sensitivity of 17.3% and specificity of 94.7%. In evaluating children, these values are 57.8% and 69.6%, respectively.⁶ If results are equivocal, a 24-hour EEG can increase the likelihood of detecting epileptiform discharges to 89% of patients.⁷ Brain MRI may detect an abnormality in 12% to 14% of patients with newly diagnosed epilepsy, and in up to 80% of those with recurrent seizures.⁸ In confirming hippocampus sclerosis, MRI has demonstrated a sensitivity of 93% and specificity of 86%.⁹

When to treat a first-time seizure. Available data and prediction models identify risk factors that would help determine whether to start an antiseizure medication after a first unprovoked seizure: abnormal EEG with particular epileptiform activity, abnormal neurologic exam, abnormal computerized tomography or MRI results, nocturnal seizure, focal seizure, or family history of seizures. In the absence of such risk factors, chances of further unprovoked seizures are not high enough to justify treatment with antiseizure medications. However, if a second unprovoked seizure were to occur, that would meet the definition of epilepsy, and treatment is indicated due to the high risk for further seizures.^10,11

Epilepsy diagnosis

The International League Against Epilepsy (ILAE) previously defined epilepsy as 2 unprovoked seizures more than 24 hours apart. However, a more recent ILAE task force modified this definition: even a single unprovoked seizure would be enough to diagnose epilepsy if there is high probability of further seizures—eg, in the presence of definitive epileptiform discharges on EEG or presence of a brain tumor or a remote brain insult on imaging, since such conditions induce an enduring predisposition to generate epileptic seizures. ² Also, a single unprovoked seizure is enough to diagnose epilepsy if it is part of an epileptic syndrome such as juvenile myoclonic epilepsy. Further, a time limit was added to the definition—ie, epilepsy is considered resolved if a patient remains seizure free for 10 years without use of antiseizure medications during the past 5 years. However, given the multitude of variables and evidence, the task force acknowledged the need for individualized considerations. ²

Seizure classification

Classification of seizure type is based on the site of seizure onset and its spread pattern—ie, focal, generalized, or unknown onset.

Continue to: Focal-onset seizures

Focal-onset seizures originate “within networks limited to one hemisphere,” although possibly in more than 1 region (ie, multifocal, and presence or absence of loss of awareness). ¹² Focal seizures may then be further classified into “motor onset” or “nonmotor onset” (eg, autonomic, emotional, sensory). ²

Generalized seizures are those “originating at some point within, and rapidly engaging, bilaterally distributed networks.” ¹³ Unlike focal-onset seizures, generalized seizures are not classified based on awareness, as most generalized seizures involve loss of awareness (absence) or total loss of consciousness (generalized tonic-clonic). They are instead categorized based on the presence of motor vs nonmotor features (eg, tonic-clonic, myoclonic, atonic). Epilepsy classification is quite dynamic and constantly updated based on new genetic, electroencephalographic, and neuroimaging discoveries.

Treatment of epilepsy

Antiseizure medications

Treatment with antiseizure medications (ASMs; formerly known as antiepileptic drugs ) is the mainstay of epilepsy management. Achieving efficacy (seizure freedom) and tolerability (minimal adverse effects) are the primary goals of treatment. Factors that should govern the selection of an ASM include the seizure type/epilepsy syndrome, adverse effect profile of the ASM, pharmacodynamic/pharmacokinetic considerations, and patient comorbidities.

Levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies.

The Standard and New Antiepileptic Drugs (SANAD I and II) trials provide data from direct, unblinded, and longitudinal comparisons of existing and new ASMs and their utility in different seizure types. In the SANAD I cohort of patients with generalized and unclassified epilepsies, valproate was superior to lamotrigine and topiramate for 12-month remission and treatment failure rates, respectively.¹⁴ However, valproate generally is avoided in women of childbearing age due its potential adverse effects during pregnancy. In focal epilepsies, lamotrigine was superior to carbamazepine, gabapentin, and topiramate with respect to treatment failure, and noninferior to carbamazepine for 12-month remission.¹⁵ In the SANAD II trial, levetiracetam was noninferior to valproate for incidence of adverse events in patients with generalized and unclassified epilepsies although was found to be neither more clinically effective nor more cost effective.¹⁶ For patients of childbearing potential with generalized and unclassified epilepsies, there is evidence to support the safe and effective use of levetiracetam.¹⁷In focal epilepsies, lamotrigine was superior to levetiracetam and zonisamide with respect to treatment failures and adverse events and was noninferior to zonisamide for 12-month remission.¹⁸ In summary, levetiracetam and valproate (not to be used in women of childbearing potential) are considered appropriate first-line agents for generalized and unclassified epilepsies while lamotrigine is deemed an appropriate first-line agent for focal epilepsies (TABLE 1^19-28).

Drug level monitoring. It is standard practice to periodically monitor serum levels in patients taking first-generation ASMs such as phenytoin, carbamazepine, phenobarbital, and valproic acid because of their narrow therapeutic range and the potential for overdose or interaction with other medications or foods (eg, grapefruit juice may increase carbamazepine serum level by inhibiting ­CYP3A4, the enzyme that metabolizes the drug). Patients taking newer ASMs may not require regular serum level monitoring except during titration, with hepatic or renal dosing, when concomitantly used with estrogen-based oral contraceptives (eg, lamotrigine), before or during pregnancy, or when nonadherence is suspected.

Continue to: Can antiseizure treatment be stopped?

Can antiseizure treatment be stopped?

Current evidence favors continuing ASM therapy in patients whose seizures are under control, although the decision should be tailored to an individual’s circumstances. According to the 2021 American Academy of Neurology (AAN) guidelines, adults who have been seizure free for at least 2 years and discontinue ASMs are possibly still at higher risk for seizure recurrence in the long term (24-60 months), compared with those who continue treatment.²⁹ On the other hand, for adults who have been seizure free for at least 12 months, ASM withdrawal may not increase their risk for status epilepticus, and there are insufficient data to support or refute an effect on mortality or quality of life with ASM withdrawal in this population. The decision to taper or maintain ASM therapy in seizure-free patients also should take into consideration other clinically relevant outcome measures such as the patient’s lifestyle and medication adverse effects. Therefore, this decision should be made after sufficient discussion with patients and their caregivers. (Information for patients can be found at: www.epilepsy.com/treatment/medicines/stopping-medication.)

There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

For children, the AAN guideline panel recommends discussing with family the small risk (2%) for becoming medication resistant if seizures recur during or after ASM withdrawal. ²⁹ For children who have been seizure free for 18 to 24 months, there is probably not a significant long-term (24-48 months) difference in seizure recurrence in those who taper ASMs vs those who do not. However, presence of epileptiform discharges on EEG before discontinuation of an ASM indicates increased risk for seizure recurrence. ²⁹

Intractable (refractory) epilepsy

While most patients with epilepsy attain complete seizure control with appropriate drug therapy, approximately 30% continue to experience seizures (“drug-resistant” epilepsy, also termed intractable or refractory ). ³⁰ In 2010, the ILAE defined drug-resistant epilepsy as “failure of adequate trials of two tolerated, appropriately chosen and used anti-epileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom” (defined as cessation of seizures for at least 3 times the longest pre-intervention inter-seizure interval or 12 months, whichever is longer). ^21,31 It should be noted that drug withdrawal due to adverse effects is not counted as failure of that ASM. Recognition of drug-resistant epilepsy may prompt referral to an epileptologist who can consider rational combination drug therapy or surgical resection of the seizure focus, vagus nerve stimulation, electrical stimulation of the seizure focus, or deep brain (thalamic) stimulation.

Seizure triggers and mitigating factors

Epilepsy mostly affects patients during seizure episodes; however, the unpredictability of these events adds significantly to the burden of disease. There are no reliable methods for predicting seizure other than knowing of the several potential risks and recognizing and avoiding these triggers.

Noncompliance with antiseizure medications is a common seizure trigger affecting up to one-half of patients with epilepsy.³²

Continue to: Medications

Medications may provoke seizures in susceptible individuals (TABLE 2^33-35).

Sleep deprivation is a potential seizure trigger in people with epilepsy based on observational studies, case reports, patient surveys, and EEG-based studies, although data from randomized controlled studies are limited.³⁶ The standard best practice is to encourage appropriate sleep hygiene, which involves getting at least 7 hours of sleep per night.³⁷

Alcohol is a GABAergic substance like benzodiazepines with antiseizure effects. However, it acts as a potential precipitant of seizures in cases of withdrawal or acute intoxication, or when it leads to sleep disruption or nonadherence to antiseizure medications. Therefore, advise patients with alcohol use disorder to slowly taper consumption (best done through a support program) and avoid sudden withdrawal. However, complete abstinence from alcohol use is not often recommended except in special circumstances (eg, a history of alcohol-related seizures). Several studies have demonstrated that modest alcohol use (1-2 drinks per occasion) does not increase seizure frequency or significantly alter serum concentrations of commonly used ASMs.³⁸

Cannabis and other substances. The 2 main biologically active components of marijuana are delta-9-tetrahydrocannibinol (THC), the main psychoactive constituent, and cannabidiol (CBD). Animal and human studies have demonstrated anticonvulsant properties of THC and CBD. But THC, in high amounts, can result in adverse cognitive effects and worsening seizures.³⁹ A purified 98% oil-based CBD extract (Epidiolex) has been approved as an adjunctive treatment for certain medically refractory epilepsy syndromes in children and young adults—ie, Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex syndrome.⁴⁰ There are no reliable data on the effect of recreational use of marijuana on seizure control. Other illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

Special clinical cases

Pregnancy and epilepsy

Despite the potential adverse effects of ASMs on fetal health, the current global consensus is to continue treatment during pregnancy, given that the potential harm of convulsive seizures outweighs the potential risks associated with in-utero exposure to ASMs. There is not enough evidence to indicate significant harm to the fetus caused by focal, absence, or myoclonic seizures. Low-dose folic acid is used to minimize the risks of ASMs during pregnancy.

Continue to: As the fetus develops...

Illicit substances such as cocaine may lower seizure threshold by their stimulatory and disruptive effects on sleep, diet, and healthy routines.

As the fetus develops, there are changes in volume of ASM distribution, renal clearance, protein binding, and hepatic metabolism, which require checking serum levels at regular intervals and making dosage adjustments.

The ongoing study evaluating Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)⁴¹ has led to multiple landmark studies guiding the choice of preferred ASMs during pregnancy in patients with epilepsy.^42,43 This has culminated in today’s use of lamotrigine and levetiracetam as the 2 preferred agents (while avoiding valproate) in pregnant patients with epilepsy.⁴⁴

Psychogenic nonepileptic seizures

Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers.

A form of conversion disorder, psychogenic nonepileptic seizures (PNES) manifests as abnormal motor or behavioral events mimicking seizures but without associated epileptiform discharges on EEG. This is observed in 10% of patients seen in epilepsy clinics and even more often in those admitted to epilepsy­ monitoring units (25%-40%).⁴⁵ Diagnosis of PNES requires EEG monitoring both for confirmation and for discernment from true epileptic seizures, in particular frontal lobe epilepsy that may clinically mimic PNES. PNES often is associated with underlying psychological tensions or comorbid conditions such as depression, anxiety, or traumatic life experiences. There is no treatment for PNES per se, and its management is focused on controlling any underlying psychological comorbidities that may not always be obvious. There is some evidence suggesting that these patients experience an innate inability to verbally express their emotions and instead subconsciously resort to psychosomatics to express them in a somatic dimension.^46,47

Status epilepticus

Defined as prolonged seizures (> 5 min) or 2 consecutive seizures without regaining aware ness in between, status epilepticus (SE) is a potentially fatal condition. Subclinical nonconvulsive SE, especially in comatose patients, can be diagnosed only via EEG monitoring. Untreated SE may manifest as a diagnostic dilemma in unresponsive or critically ill patients and can increase the risk for mortality. ⁴⁸

Febrile seizures

Febrile seizures affect 2% to 5% of children most often in the second year of life.⁴⁹ The use of preventive antiseizure medication is not recommended; instead, the key is to investigate the underlying febrile illness. Lumbar puncture is indicated if there are signs and symptoms of meningitis (25% of children with bacterial meningitis present with seizures).⁴⁹ Febrile seizures often are self-limited, but there is risk for SE in up to 15% of cases.⁵⁰ If convulsive febrile seizures last longer than 5 minutes, initiate benzodiazepines followed by the standard protocol used for the management of SE.⁵¹

Continue to: Epilepsy as a spectrum disorder

The higher prevalence of comorbid cognitive and psychiatric conditions in patients with epilepsy, affecting about half of patients, ⁵² suggests that seizures may constitute only one aspect of a multifaceted disease that otherwise should be considered a spectrum disorder. Among such conditions are memory deficits, depression, and anxiety. Conversely, epilepsy is more common in patients with depression than in those without. ⁵²

Social impact of epilepsy

De-escalation of treatment offers an equivalent, resource-sparing alternative to traditional treatment of pediatric torus fractures of the distal radius.

Vehicle driving regulations. Patients with epilepsy are required to follow state law regarding driving restrictions. Different states have different rules and regulations about driving restrictions and reporting requirements (by patients or their physicians). Refer patients to the Department of Motor Vehicles (DMV) in their state of residence for up-to-date instructions.⁵³ The Epilepsy Foundation (epilepsy.com) can serve as a resource for each state’s DMV website.

Employment assistance. Having epilepsy should not preclude patients from seeking employment and pursuing meaningful careers. The Americans with Disabilities Act (ADA) and the US Equal Employment Opportunity Commission (EEOC) forbid discrimination against qualified people with disabilities, including those with epilepsy, and require reasonable accommodations in the workplace (www.eeoc.gov/laws/guidance/­epilepsy-workplace-and-ada).⁵⁴

CORRESPONDENCE
Gholam K. Motamedi, MD, Department of Neurology, PHC 7, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC 20007; [email protected]

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Essential oils (EOs), which are concentrated plant-based oils, have become ubiquitous over the past decade. ­Given the far reach of EOs and their longtime use in traditional, complementary, alternative, and integrative medicine, it is imperative that clinicians have some knowledge of the potential benefits, risks, and overall efficacy.

Commonly used for aromatic benefits (aromatherapy), EOs are now also incorporated into a multitude of products promoting health and wellness. EOs are sold as individual products and can be a component in consumer goods such as cosmetics, body care/hygiene/beauty products, laundry detergents, insect repellents, over-the-counter medications, and food.

It is important to read ingredient labels before purchasing an essential oil. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process.

The review that follows presents the most current evidence available. With that said, it’s important to keep in mind some caveats that relate to this evidence. First, the studies cited tend to have a small sample size. Second, a majority of these studies were conducted in countries where there appears to be a significant culture of EO use, which could contribute to confirmation bias. Finally, in a number of the studies, there is concern for publication bias as well as a discrepancy between calculated statistical significance and actual clinical relevance.

What are essential oils?

EOs generally are made by extracting the oil from leaves, bark, flowers, seeds/fruit, rinds, and/or roots by steaming or pressing parts of a plant. It can take several pounds of plant material to produce a single bottle of EO, which usually contains ≥ 15 to 30 mL (.5 to 1 oz).¹

Some commonly used EOs in the United States are lavender, peppermint, rose, clary sage, tea tree, eucalyptus, and citrus; however, there are approximately 300 EOs available.² EOs are used most often via topical application, inhalation, or ingestion.

As with any botanical agent, EOs are complex substances often containing a multitude of chemical compounds.¹ Because of the complex makeup of EOs, which often contain up to 100 volatile organic compounds, and their wide-ranging potential effects, applying the scientific method to study effectiveness poses a challenge that has limited their adoption in evidence-based practice.²

Availability and cost. EOs can be purchased at large retailers (eg, grocery stores, drug stores) and smaller health food stores, as well as on the Internet. Various EO vehicles, such as inhalers and topical creams, also can be purchased at these stores.

Continue to: The cost varies...

The cost varies enormously by manufacturer and type of plant used to make the EO. Common EOs such as peppermint and lavender oil generally cost $10 to $25, while rarer plant oils can cost $80 or more per bottle.

How safe are essential oils?

Patients may assume EOs are harmless because they are derived from natural plants and have been used medicinally for centuries. However, care must be taken with their use.

The safest way to use EOs is topically, although due to their highly concentrated nature, EOs should be diluted in an unscented neutral carrier oil such as coconut, jojoba, olive, or sweet almond.³ Ingestion of certain oils can cause hepatotoxicity, seizures, and even death.³ In fact, patients should speak with a knowledgeable physician before purchasing any oral EO capsules.

Whether used topically or ingested, all EOs carry risk for skin irritation and allergic reactions, and oral ingestion may result in some negative gastrointestinal (GI) adverse effects.⁴ A case report of 3 patients published in 2007 identified the potential for lavender and tea tree EOs to be endocrine disruptors.⁵

Inhalation of EOs may be harmful, as they emit many volatile organic compounds, some of which are considered potentially hazardous.⁶ At this time, there is insufficient evidence regarding inhaled EOs and their direct connection to respiratory health. It is reasonable to suggest, however, that the prolonged use of EOs and their use by patients who have lung conditions such as asthma or COPD should be avoided.⁷

Continue to: How are quality and purity assessed?

How are quality and purity assessed?

Like other dietary supplements, EOs are not regulated. No US regulatory agencies (eg, the US Food and Drug Administration [FDA] or Department of Agriculture [USDA]) certify or approve EOs for quality and purity. Bottles labeled with “QAI” for Quality Assurance International or “USDA Organic” will ensure the plant constituents used in the EO are from organic farming but do not attest to quality or purity.

Essential oils are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for adjunctive treatment of migraine and tension-type headaches.

Manufacturers commonly use marketing terms such as “therapeutic grade” or “pure” to sell products, but again, these terms do not reflect the product’s quality or purity. A labeled single EO may contain contaminants, alcohol, or additional ingredients.⁷ When choosing to use EOs, identifying reputable brands is essential; one resource is the independent testing organization ConsumerLab.com.

It is important to assess the manufacturer and read ingredient labels before purchasing an EO to understand what the product contains. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process. A more certain way to assess the quality and purity of an EO is to ask the manufacturer to provide a certificate of analysis and gas chromatography/mass spectroscopy (GC/MS) data for the specific product. Some manufacturers offer GC/MS test results on their website Quality page.⁸ Others have detailed information on quality and testing, and GC/MS test reports can be obtained.⁹ Yet another manufacturer has test results on a product page matching reports to batch codes.¹⁰

Which conditions have evidence of benefit from essential oils?

EOs currently are being studied for treatment of many conditions—including pain, GI disorders, behavioral health disorders, and women’s health issues. The TABLE summarizes the conditions treated, outcomes, and practical applications of EOs.^11-44

Pain

Headache. As an adjunct to available medications and procedures for headache treatment, EOs are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for both migraine and ­tension-type headaches. A systematic review of 19 randomized controlled trials (RCTs) examining the effects of herbal ingredients for the acute treatment or prophylaxis of migraines found certain topically applied or inhaled EOs, such as peppermint and chamomile, to be effective for migraine pain alleviation; however, topically applied rose oil was not effective.^11-13 Note: “topical application” in these studies implies application of the EO to ≥ 1 of the following areas: temples, forehead, behind ears, or above upper lip/below the nose.

Continue to: One RCT with 120 patients...

One RCT with 120 patients evaluated diluted intranasal peppermint oil and found that it reduced migraine intensity at similar rates to intranasal lidocaine.¹³ In this study, patients were randomized to receive one of the following: 4% lidocaine, 1.5% peppermint EO, or placebo. Two drops of the intranasal intervention were self-administered while the patient was in a supine position with their head suspended off the edge of the surface on which they were lying. They were instructed to stay in this position for at least 30 seconds after administration.

With regard to tension headache treatment, there is limited literature on the use of EOs. One study found that a preparation of peppermint oil applied topically to the temples and forehead of study participants resulted in significant analgesic effect.¹⁴

Fibromyalgia. Usual treatments for fibromyalgia include exercise, antidepressant and anticonvulsant medications, and stress management. Evidence also supports the use of inhaled and topically applied (with and without massage) lavender oil to improve symptoms.²⁶ Positive effects may be related to the anal­gesic, anti-­inflammatory, sleep-regulating,­ and anxiety­-reducing effects of the major volatile compounds contained in lavender oil.

In one RCT with 42 patients with fibromyalgia, the use of inhaled lavender oil was shown to increase the perception of well-­being (assessed on the validated SF-36 Health Survey Questionnaire) after 4 weeks.²⁷ In this study, the patient applied 3 drops of an oil mixture, comprising 1 mL lavender EO and 10 mL of fixed neutral base oil, to the wrist and inhaled for 10 minutes before going to bed.

The use of a topical oil blend labeled “Oil 24” (containing camphor, rosemary, eucalyptus, peppermint, aloe vera, and lemon/orange) also has been shown to be more effective than placebo in managing fibromyalgia symptoms. A randomized controlled pilot study of 153 participants found that regular application of Oil 24 improved scores on pain scales and the Fibromyalgia Impact Questionnaire.²⁸

Continue to: GI disorders

GI disorders

Irritable bowel syndrome. Peppermint oil relaxes GI smooth muscle, which has led to investigation of its use in irritable bowel ­syndrome (IBS) symptom amelioration.¹⁷ One meta-analysis including 12 RCTs with 835 patients with undifferentiated IBS found that orally ingested peppermint EO capsules reduced patient-reported symptoms of either abdominal pain or global symptoms.¹⁸

One study utilized the Total IBS Symptom Score to evaluate symptom reduction in patients with IBS-D (with diarrhea) and IBS-M (mixed) using 180-mg peppermint EO capsules ingested 3 times daily. There was a significant improvement in abdominal pain/discomfort, bloating/distension, pain at evacuation, and bowel urgency.¹⁹ A reduction in symptoms was observed after the first 24 hours of treatment and at the end of the 4-week treatment period.

In another study, among the 190 patients meeting Rome IV criteria for general (nonspecific) IBS who were treated with 182-mg peppermint EO capsules, no statistically significant reduction in overall symptom relief was found (based on outcome measures by the FDA and European Medicines Agency). However, in a secondary outcome analysis, peppermint oil produced greater improvements than placebo for the alleviation of abdominal pain, discomfort, and general IBS severity.²⁰

Chemotherapy-induced nausea and vomiting. Patients with cancer undergoing chemotherapy often explore integrative medicine approaches, including aromatherapy, to ameliorate adverse effects and improve quality of life.³⁸ A few small studies have shown potential for the use of inhaled ginger oil to reduce nausea and vomiting severity and improve health-related quality-of-life measures in these patients.

Evidence supports the use of inhaled and topically applied lavender oil to improve fibromyalgia symptoms.

For example, a study with 60 participants found that inhaling ginger EO for 10 minutes was beneficial for reducing both nausea and vomiting.³⁹ A single-blind, controlled, ­randomized crossover study of 60 patients with breast cancer receiving chemotherapy showed that ginger EO inhaled 3 times per day for 2 minutes at a time can decrease the severity of nausea but had no effect on vomiting. The same study showed that health-­related quality of life improved with the ginger oil treatment.⁴⁰

Continue to: Other EOs such as cardamom...

Other EOs such as cardamom and peppermint show promise as an adjunctive treatment for chemotherapy-induced nausea and vomiting as well.³⁸

Postoperative nausea. A 2013 randomized trial of 303 patients examined the use of ginger EO, a blend of EOs (including ginger, spearmint, peppermint, and cardamom), and isopropyl alcohol. Both the single EO and EO blend significantly reduced the symptom of nausea. The number of antiemetic medications requested by patients receiving an EO also was significantly reduced compared to those receiving saline.¹⁵

The use of EOs to reduce nausea after cardiac operations was reviewed in an RCT of 60 surgical candidates using 10% peppermint oil via nebulization for 10 minutes.¹⁶ This technique was effective in reducing nausea during cardiac postoperative periods. Although the evidence for the use of EOs for postoperative nausea is not robust, it may be a useful and generally safe approach for this common issue.

Behavioral health

Insomnia. EOs have been used as a treatment for insomnia traditionally and in complementary, alternative, and integrative medicine. A 2014 systematic review of 15 quantitative studies, including 11 RCTs, evaluated the hypnotic effects of EOs through inhalation, finding the strongest evidence for lavender, jasmine, and peppermint oils.²⁹ The majority of the studies in the systematic review used the Pittsburgh Sleep Quality Index (PSQI) to evaluate EO effectiveness. A more recent 2021 systematic review and meta-analysis that evaluated 34 RCTs found that inhalation of EOs, most notably lavender aromatherapy, is effective in improving sleep problems such as insomnia.³⁰

Findings from multiple smaller RCTs were consistent with those of the aforementioned systematic reviews. For example, in a well-conducted parallel randomized double-blind placebo-controlled trial of 100 people using orally ingested lemon verbena, the authors concluded that this intervention can be a complementary therapy for improving sleep quality and reducing insomnia severity.³¹ Another RCT with 60 participants evaluated an inhaled EO blend (lemon, eucalyptus, tea tree, and peppermint) over 4 weeks and found lowered perceived stress and depression as well as better sleep quality, but no influence on objective physiologic data such as stress indices or immune states.³²

Continue to: In a 2020 randomized crossover...

In a 2020 randomized crossover placebo­controlled trial of 37 participants with diabetes reporting insomnia, inhaled lavender improved sleep quality and quantity, quality of life, and mood but not physiologic or metabolic measures, such as fasting glucose.³³ Findings were similar in a cohort of cardiac rehabilitation patients (n = 37) who were treated with either an inhaled combination of lavender, bergamot, and ylang ylang, or placebo; cotton balls infused with the intervention oil or placebo oil were placed at the patient’s bedside for 5 nights. Sleep quality of participants receiving intervention oil was significantly better than the sleep quality of participants receiving the placebo oil as measured by participant completion of the PSQI.³⁴

Anxiety is a common disorder that can be managed with nonpharmacologic treatments such as yoga, deep breathing, meditation, and EO therapy.^21,22 In a systematic review and meta-analysis, the inhaled and topical use (with or without massage) of lavender EO was shown to improve psychological and physical manifestations of anxiety.²³ Lavender EO is purported to affect the parasympathetic nervous system via anxiolytic, sedative, analgesic, and anticonvulsant properties.²⁴ One systematic review and meta-analysis evaluating the anxiolytic effect of both inhaled and topical lavender EO found improvement in several biomarkers and physiologic data including blood pressure, heart rate, and cortisol levels, as well as a reduction in self-reported levels of anxiety, compared with placebo.²⁵

Anxiety related to dental procedures is another area of study for the use of EOs. Two RCTs demonstrate statistically significant improvement in anxiety-related physiologic markers such as heart rate, blood pressure, and salivary cortisol levels in children who inhaled lavender EO during dental procedures.^41,42 In 1 of the RCTs, the intervention was described as 3 drops of 100% lavender EO applied to a cloth and inhaled over the course of 3 minutes.⁴¹ Additionally, 2 studies found that orange EO was beneficial for dental procedure–induced anxiety, reducing pulse rates, cortisol levels, and self-reported anxiety.^43,44

Dementia-related behavioral disturbances. A small, poorly designed study examining 2 EO blends—rosemary with lemon and lavender with orange—found some potential for improving cognitive function, especially in patients with Alzheimer disease.⁴⁵ A Cochrane review of 13 RCTs totaling 708 patients concluded that it is not certain from the available evidence that EO therapy benefits patients with dementia in long-term-care facilities and hospital wards.⁴⁶ Given that reporting of adverse events in the trials was poor, it is not possible to make conclusions about the risk vs benefit of EO therapy in this population.

Women’s health

Dysmenorrhea. Interest has grown in the use of EOs for dysmenorrhea symptom relief, and there is a small body of evidence demonstrating that a variety of oils—most notably lavender, rose, and clary sage—may reduce symptom severity. One meta-analysis of 9 RCTs and 12 controlled clinical trials including women with moderate-to-severe dysmenorrhea found that inhaled and/or topical use of singular or mixed lavender, clary sage, rose, marjoram, and cinnamon EOs demonstrated the strongest evidence of effectiveness in reducing menstrual cramping.³⁵

Continue to: In a randomized, double-blind clinical trial...

Use of an inhaled blend of lemon, eucalyptus, tea tree, and peppermint was associated with lower perceived stress and depression as well as better sleep quality.

In a randomized, double-blind clinical trial of 48 women, a cream-based blend of lavender, clary sage, and marjoram EO (used topically in a 2:1:1 ratio diluted in unscented cream at 3% concentration and applied daily via abdominal massage) reduced participants’ reported menstrual pain symptoms and duration of pain.³⁶ In a meta-analysis of 6 studies, topical abdominal application of EO (mainly lavender with or without other oils) with massage showed superiority over massage with placebo oils in reducing menstrual pain.³⁷ A reduction in pain, mood symptoms, and fatigue in women with premenstrual symptoms was seen in an RCT of 77 patients using 3 drops of inhaled lavender EO.⁴⁷

Labor. There is limited evidence for the use of EOs during labor. In an RCT of 104 women, patient-selected diffused EOs, including lavender, rose geranium, citrus, or jasmine, were found to help lower pain scores during the latent and early active phase of labor. There were no differences in labor augmentation, length of labor, perinatal outcomes, or need for additional pain medication.⁴⁸

Other uses

Antimicrobial support. Some common EOs that have demonstrated antimicrobial properties are oregano, thyme, clove, lavender, clary sage, garlic, and cinnamon.^49,50 Topical lemongrass and tea tree EOs have shown some degree of efficacy as an alternative treatment for acne, decolonization of methicillin-resistant Staphylococcus aureus, and superficial fungal infections.⁵¹ Support for an oral mixture of EOs labeled Myrtol (containing eucalyptus, citrus myrtle, and lavender) for viral acute bronchitis and sinusitis was found in a review of 7 studies.⁵² More research needs to be done before clear recommendations can be made on the use of EOs as antimicrobials, but the current data are encouraging.

Insect repellent. Reviews of the ­insect-repellent properties of EOs have shown promise and are in the public’s interest due to increasing awareness of the potential health and environmental hazards of synthetic repellents.⁵³ Individual compounds present in EOs such as citronella/lemongrass, basil, and eucalyptus species demonstrate high repellent activity.⁵⁴ Since EOs require frequent reapplication for efficacy due to their highly volatile nature, scientists are currently developing a means to prolong their protection time through cream-based formulations.⁵⁵

The bottom line

Because of the ubiquity of EOs, family physicians will undoubtedly be asked about them by patients, and it would be beneficial to feel comfortable discussing their most common uses. For most adult patients, the topical and periodic inhaled usage of EOs is generally safe.⁵⁶

There is a small body of evidence demonstrating that a variety of essential oils, most notably lavender, rose, and clary sage, may reduce dysmenorrhea symptom severity.

There is existing evidence of efficacy for a number of EOs, most strongly for lavender and peppermint. Future research into EOs should include higher-powered and higher-­quality studies in order to provide more conclusive evidence regarding the continued use of EOs for many common conditions. More evidence-based information on dosing, application/use regimens, and safety in long-term use also will help providers better instruct patients on how to utilize EOs effectively and safely. 

CORRESPONDENCE
Pooja Amy Shah, MD, Columbia University College of Physicians & Surgeons, 610 West 158th Street, New York, NY 10032; [email protected]

Essential oils (EOs), which are concentrated plant-based oils, have become ubiquitous over the past decade. ­Given the far reach of EOs and their longtime use in traditional, complementary, alternative, and integrative medicine, it is imperative that clinicians have some knowledge of the potential benefits, risks, and overall efficacy.

Commonly used for aromatic benefits (aromatherapy), EOs are now also incorporated into a multitude of products promoting health and wellness. EOs are sold as individual products and can be a component in consumer goods such as cosmetics, body care/hygiene/beauty products, laundry detergents, insect repellents, over-the-counter medications, and food.

It is important to read ingredient labels before purchasing an essential oil. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process.

The review that follows presents the most current evidence available. With that said, it’s important to keep in mind some caveats that relate to this evidence. First, the studies cited tend to have a small sample size. Second, a majority of these studies were conducted in countries where there appears to be a significant culture of EO use, which could contribute to confirmation bias. Finally, in a number of the studies, there is concern for publication bias as well as a discrepancy between calculated statistical significance and actual clinical relevance.

What are essential oils?

EOs generally are made by extracting the oil from leaves, bark, flowers, seeds/fruit, rinds, and/or roots by steaming or pressing parts of a plant. It can take several pounds of plant material to produce a single bottle of EO, which usually contains ≥ 15 to 30 mL (.5 to 1 oz).¹

Some commonly used EOs in the United States are lavender, peppermint, rose, clary sage, tea tree, eucalyptus, and citrus; however, there are approximately 300 EOs available.² EOs are used most often via topical application, inhalation, or ingestion.

As with any botanical agent, EOs are complex substances often containing a multitude of chemical compounds.¹ Because of the complex makeup of EOs, which often contain up to 100 volatile organic compounds, and their wide-ranging potential effects, applying the scientific method to study effectiveness poses a challenge that has limited their adoption in evidence-based practice.²

Availability and cost. EOs can be purchased at large retailers (eg, grocery stores, drug stores) and smaller health food stores, as well as on the Internet. Various EO vehicles, such as inhalers and topical creams, also can be purchased at these stores.

Continue to: The cost varies...

The cost varies enormously by manufacturer and type of plant used to make the EO. Common EOs such as peppermint and lavender oil generally cost $10 to $25, while rarer plant oils can cost $80 or more per bottle.

How safe are essential oils?

Patients may assume EOs are harmless because they are derived from natural plants and have been used medicinally for centuries. However, care must be taken with their use.

The safest way to use EOs is topically, although due to their highly concentrated nature, EOs should be diluted in an unscented neutral carrier oil such as coconut, jojoba, olive, or sweet almond.³ Ingestion of certain oils can cause hepatotoxicity, seizures, and even death.³ In fact, patients should speak with a knowledgeable physician before purchasing any oral EO capsules.

Whether used topically or ingested, all EOs carry risk for skin irritation and allergic reactions, and oral ingestion may result in some negative gastrointestinal (GI) adverse effects.⁴ A case report of 3 patients published in 2007 identified the potential for lavender and tea tree EOs to be endocrine disruptors.⁵

Inhalation of EOs may be harmful, as they emit many volatile organic compounds, some of which are considered potentially hazardous.⁶ At this time, there is insufficient evidence regarding inhaled EOs and their direct connection to respiratory health. It is reasonable to suggest, however, that the prolonged use of EOs and their use by patients who have lung conditions such as asthma or COPD should be avoided.⁷

Continue to: How are quality and purity assessed?

How are quality and purity assessed?

Like other dietary supplements, EOs are not regulated. No US regulatory agencies (eg, the US Food and Drug Administration [FDA] or Department of Agriculture [USDA]) certify or approve EOs for quality and purity. Bottles labeled with “QAI” for Quality Assurance International or “USDA Organic” will ensure the plant constituents used in the EO are from organic farming but do not attest to quality or purity.

Essential oils are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for adjunctive treatment of migraine and tension-type headaches.

Manufacturers commonly use marketing terms such as “therapeutic grade” or “pure” to sell products, but again, these terms do not reflect the product’s quality or purity. A labeled single EO may contain contaminants, alcohol, or additional ingredients.⁷ When choosing to use EOs, identifying reputable brands is essential; one resource is the independent testing organization ConsumerLab.com.

It is important to assess the manufacturer and read ingredient labels before purchasing an EO to understand what the product contains. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process. A more certain way to assess the quality and purity of an EO is to ask the manufacturer to provide a certificate of analysis and gas chromatography/mass spectroscopy (GC/MS) data for the specific product. Some manufacturers offer GC/MS test results on their website Quality page.⁸ Others have detailed information on quality and testing, and GC/MS test reports can be obtained.⁹ Yet another manufacturer has test results on a product page matching reports to batch codes.¹⁰

Which conditions have evidence of benefit from essential oils?

EOs currently are being studied for treatment of many conditions—including pain, GI disorders, behavioral health disorders, and women’s health issues. The TABLE summarizes the conditions treated, outcomes, and practical applications of EOs.^11-44

Pain

Headache. As an adjunct to available medications and procedures for headache treatment, EOs are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for both migraine and ­tension-type headaches. A systematic review of 19 randomized controlled trials (RCTs) examining the effects of herbal ingredients for the acute treatment or prophylaxis of migraines found certain topically applied or inhaled EOs, such as peppermint and chamomile, to be effective for migraine pain alleviation; however, topically applied rose oil was not effective.^11-13 Note: “topical application” in these studies implies application of the EO to ≥ 1 of the following areas: temples, forehead, behind ears, or above upper lip/below the nose.

Continue to: One RCT with 120 patients...

One RCT with 120 patients evaluated diluted intranasal peppermint oil and found that it reduced migraine intensity at similar rates to intranasal lidocaine.¹³ In this study, patients were randomized to receive one of the following: 4% lidocaine, 1.5% peppermint EO, or placebo. Two drops of the intranasal intervention were self-administered while the patient was in a supine position with their head suspended off the edge of the surface on which they were lying. They were instructed to stay in this position for at least 30 seconds after administration.

With regard to tension headache treatment, there is limited literature on the use of EOs. One study found that a preparation of peppermint oil applied topically to the temples and forehead of study participants resulted in significant analgesic effect.¹⁴

Fibromyalgia. Usual treatments for fibromyalgia include exercise, antidepressant and anticonvulsant medications, and stress management. Evidence also supports the use of inhaled and topically applied (with and without massage) lavender oil to improve symptoms.²⁶ Positive effects may be related to the anal­gesic, anti-­inflammatory, sleep-regulating,­ and anxiety­-reducing effects of the major volatile compounds contained in lavender oil.

In one RCT with 42 patients with fibromyalgia, the use of inhaled lavender oil was shown to increase the perception of well-­being (assessed on the validated SF-36 Health Survey Questionnaire) after 4 weeks.²⁷ In this study, the patient applied 3 drops of an oil mixture, comprising 1 mL lavender EO and 10 mL of fixed neutral base oil, to the wrist and inhaled for 10 minutes before going to bed.

The use of a topical oil blend labeled “Oil 24” (containing camphor, rosemary, eucalyptus, peppermint, aloe vera, and lemon/orange) also has been shown to be more effective than placebo in managing fibromyalgia symptoms. A randomized controlled pilot study of 153 participants found that regular application of Oil 24 improved scores on pain scales and the Fibromyalgia Impact Questionnaire.²⁸

Continue to: GI disorders

GI disorders

Irritable bowel syndrome. Peppermint oil relaxes GI smooth muscle, which has led to investigation of its use in irritable bowel ­syndrome (IBS) symptom amelioration.¹⁷ One meta-analysis including 12 RCTs with 835 patients with undifferentiated IBS found that orally ingested peppermint EO capsules reduced patient-reported symptoms of either abdominal pain or global symptoms.¹⁸

One study utilized the Total IBS Symptom Score to evaluate symptom reduction in patients with IBS-D (with diarrhea) and IBS-M (mixed) using 180-mg peppermint EO capsules ingested 3 times daily. There was a significant improvement in abdominal pain/discomfort, bloating/distension, pain at evacuation, and bowel urgency.¹⁹ A reduction in symptoms was observed after the first 24 hours of treatment and at the end of the 4-week treatment period.

In another study, among the 190 patients meeting Rome IV criteria for general (nonspecific) IBS who were treated with 182-mg peppermint EO capsules, no statistically significant reduction in overall symptom relief was found (based on outcome measures by the FDA and European Medicines Agency). However, in a secondary outcome analysis, peppermint oil produced greater improvements than placebo for the alleviation of abdominal pain, discomfort, and general IBS severity.²⁰

Chemotherapy-induced nausea and vomiting. Patients with cancer undergoing chemotherapy often explore integrative medicine approaches, including aromatherapy, to ameliorate adverse effects and improve quality of life.³⁸ A few small studies have shown potential for the use of inhaled ginger oil to reduce nausea and vomiting severity and improve health-related quality-of-life measures in these patients.

Evidence supports the use of inhaled and topically applied lavender oil to improve fibromyalgia symptoms.

For example, a study with 60 participants found that inhaling ginger EO for 10 minutes was beneficial for reducing both nausea and vomiting.³⁹ A single-blind, controlled, ­randomized crossover study of 60 patients with breast cancer receiving chemotherapy showed that ginger EO inhaled 3 times per day for 2 minutes at a time can decrease the severity of nausea but had no effect on vomiting. The same study showed that health-­related quality of life improved with the ginger oil treatment.⁴⁰

Continue to: Other EOs such as cardamom...

Other EOs such as cardamom and peppermint show promise as an adjunctive treatment for chemotherapy-induced nausea and vomiting as well.³⁸

Postoperative nausea. A 2013 randomized trial of 303 patients examined the use of ginger EO, a blend of EOs (including ginger, spearmint, peppermint, and cardamom), and isopropyl alcohol. Both the single EO and EO blend significantly reduced the symptom of nausea. The number of antiemetic medications requested by patients receiving an EO also was significantly reduced compared to those receiving saline.¹⁵

The use of EOs to reduce nausea after cardiac operations was reviewed in an RCT of 60 surgical candidates using 10% peppermint oil via nebulization for 10 minutes.¹⁶ This technique was effective in reducing nausea during cardiac postoperative periods. Although the evidence for the use of EOs for postoperative nausea is not robust, it may be a useful and generally safe approach for this common issue.

Behavioral health

Insomnia. EOs have been used as a treatment for insomnia traditionally and in complementary, alternative, and integrative medicine. A 2014 systematic review of 15 quantitative studies, including 11 RCTs, evaluated the hypnotic effects of EOs through inhalation, finding the strongest evidence for lavender, jasmine, and peppermint oils.²⁹ The majority of the studies in the systematic review used the Pittsburgh Sleep Quality Index (PSQI) to evaluate EO effectiveness. A more recent 2021 systematic review and meta-analysis that evaluated 34 RCTs found that inhalation of EOs, most notably lavender aromatherapy, is effective in improving sleep problems such as insomnia.³⁰

Findings from multiple smaller RCTs were consistent with those of the aforementioned systematic reviews. For example, in a well-conducted parallel randomized double-blind placebo-controlled trial of 100 people using orally ingested lemon verbena, the authors concluded that this intervention can be a complementary therapy for improving sleep quality and reducing insomnia severity.³¹ Another RCT with 60 participants evaluated an inhaled EO blend (lemon, eucalyptus, tea tree, and peppermint) over 4 weeks and found lowered perceived stress and depression as well as better sleep quality, but no influence on objective physiologic data such as stress indices or immune states.³²

Continue to: In a 2020 randomized crossover...

In a 2020 randomized crossover placebo­controlled trial of 37 participants with diabetes reporting insomnia, inhaled lavender improved sleep quality and quantity, quality of life, and mood but not physiologic or metabolic measures, such as fasting glucose.³³ Findings were similar in a cohort of cardiac rehabilitation patients (n = 37) who were treated with either an inhaled combination of lavender, bergamot, and ylang ylang, or placebo; cotton balls infused with the intervention oil or placebo oil were placed at the patient’s bedside for 5 nights. Sleep quality of participants receiving intervention oil was significantly better than the sleep quality of participants receiving the placebo oil as measured by participant completion of the PSQI.³⁴

Anxiety is a common disorder that can be managed with nonpharmacologic treatments such as yoga, deep breathing, meditation, and EO therapy.^21,22 In a systematic review and meta-analysis, the inhaled and topical use (with or without massage) of lavender EO was shown to improve psychological and physical manifestations of anxiety.²³ Lavender EO is purported to affect the parasympathetic nervous system via anxiolytic, sedative, analgesic, and anticonvulsant properties.²⁴ One systematic review and meta-analysis evaluating the anxiolytic effect of both inhaled and topical lavender EO found improvement in several biomarkers and physiologic data including blood pressure, heart rate, and cortisol levels, as well as a reduction in self-reported levels of anxiety, compared with placebo.²⁵

Anxiety related to dental procedures is another area of study for the use of EOs. Two RCTs demonstrate statistically significant improvement in anxiety-related physiologic markers such as heart rate, blood pressure, and salivary cortisol levels in children who inhaled lavender EO during dental procedures.^41,42 In 1 of the RCTs, the intervention was described as 3 drops of 100% lavender EO applied to a cloth and inhaled over the course of 3 minutes.⁴¹ Additionally, 2 studies found that orange EO was beneficial for dental procedure–induced anxiety, reducing pulse rates, cortisol levels, and self-reported anxiety.^43,44

Dementia-related behavioral disturbances. A small, poorly designed study examining 2 EO blends—rosemary with lemon and lavender with orange—found some potential for improving cognitive function, especially in patients with Alzheimer disease.⁴⁵ A Cochrane review of 13 RCTs totaling 708 patients concluded that it is not certain from the available evidence that EO therapy benefits patients with dementia in long-term-care facilities and hospital wards.⁴⁶ Given that reporting of adverse events in the trials was poor, it is not possible to make conclusions about the risk vs benefit of EO therapy in this population.

Women’s health

Dysmenorrhea. Interest has grown in the use of EOs for dysmenorrhea symptom relief, and there is a small body of evidence demonstrating that a variety of oils—most notably lavender, rose, and clary sage—may reduce symptom severity. One meta-analysis of 9 RCTs and 12 controlled clinical trials including women with moderate-to-severe dysmenorrhea found that inhaled and/or topical use of singular or mixed lavender, clary sage, rose, marjoram, and cinnamon EOs demonstrated the strongest evidence of effectiveness in reducing menstrual cramping.³⁵

Continue to: In a randomized, double-blind clinical trial...

Use of an inhaled blend of lemon, eucalyptus, tea tree, and peppermint was associated with lower perceived stress and depression as well as better sleep quality.

In a randomized, double-blind clinical trial of 48 women, a cream-based blend of lavender, clary sage, and marjoram EO (used topically in a 2:1:1 ratio diluted in unscented cream at 3% concentration and applied daily via abdominal massage) reduced participants’ reported menstrual pain symptoms and duration of pain.³⁶ In a meta-analysis of 6 studies, topical abdominal application of EO (mainly lavender with or without other oils) with massage showed superiority over massage with placebo oils in reducing menstrual pain.³⁷ A reduction in pain, mood symptoms, and fatigue in women with premenstrual symptoms was seen in an RCT of 77 patients using 3 drops of inhaled lavender EO.⁴⁷

Labor. There is limited evidence for the use of EOs during labor. In an RCT of 104 women, patient-selected diffused EOs, including lavender, rose geranium, citrus, or jasmine, were found to help lower pain scores during the latent and early active phase of labor. There were no differences in labor augmentation, length of labor, perinatal outcomes, or need for additional pain medication.⁴⁸

Other uses

Antimicrobial support. Some common EOs that have demonstrated antimicrobial properties are oregano, thyme, clove, lavender, clary sage, garlic, and cinnamon.^49,50 Topical lemongrass and tea tree EOs have shown some degree of efficacy as an alternative treatment for acne, decolonization of methicillin-resistant Staphylococcus aureus, and superficial fungal infections.⁵¹ Support for an oral mixture of EOs labeled Myrtol (containing eucalyptus, citrus myrtle, and lavender) for viral acute bronchitis and sinusitis was found in a review of 7 studies.⁵² More research needs to be done before clear recommendations can be made on the use of EOs as antimicrobials, but the current data are encouraging.

Insect repellent. Reviews of the ­insect-repellent properties of EOs have shown promise and are in the public’s interest due to increasing awareness of the potential health and environmental hazards of synthetic repellents.⁵³ Individual compounds present in EOs such as citronella/lemongrass, basil, and eucalyptus species demonstrate high repellent activity.⁵⁴ Since EOs require frequent reapplication for efficacy due to their highly volatile nature, scientists are currently developing a means to prolong their protection time through cream-based formulations.⁵⁵

The bottom line

Because of the ubiquity of EOs, family physicians will undoubtedly be asked about them by patients, and it would be beneficial to feel comfortable discussing their most common uses. For most adult patients, the topical and periodic inhaled usage of EOs is generally safe.⁵⁶

There is a small body of evidence demonstrating that a variety of essential oils, most notably lavender, rose, and clary sage, may reduce dysmenorrhea symptom severity.

There is existing evidence of efficacy for a number of EOs, most strongly for lavender and peppermint. Future research into EOs should include higher-powered and higher-­quality studies in order to provide more conclusive evidence regarding the continued use of EOs for many common conditions. More evidence-based information on dosing, application/use regimens, and safety in long-term use also will help providers better instruct patients on how to utilize EOs effectively and safely. 

CORRESPONDENCE
Pooja Amy Shah, MD, Columbia University College of Physicians & Surgeons, 610 West 158th Street, New York, NY 10032; [email protected]

Essential oils (EOs), which are concentrated plant-based oils, have become ubiquitous over the past decade. ­Given the far reach of EOs and their longtime use in traditional, complementary, alternative, and integrative medicine, it is imperative that clinicians have some knowledge of the potential benefits, risks, and overall efficacy.

Commonly used for aromatic benefits (aromatherapy), EOs are now also incorporated into a multitude of products promoting health and wellness. EOs are sold as individual products and can be a component in consumer goods such as cosmetics, body care/hygiene/beauty products, laundry detergents, insect repellents, over-the-counter medications, and food.

It is important to read ingredient labels before purchasing an essential oil. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process.

The review that follows presents the most current evidence available. With that said, it’s important to keep in mind some caveats that relate to this evidence. First, the studies cited tend to have a small sample size. Second, a majority of these studies were conducted in countries where there appears to be a significant culture of EO use, which could contribute to confirmation bias. Finally, in a number of the studies, there is concern for publication bias as well as a discrepancy between calculated statistical significance and actual clinical relevance.

What are essential oils?

EOs generally are made by extracting the oil from leaves, bark, flowers, seeds/fruit, rinds, and/or roots by steaming or pressing parts of a plant. It can take several pounds of plant material to produce a single bottle of EO, which usually contains ≥ 15 to 30 mL (.5 to 1 oz).¹

Some commonly used EOs in the United States are lavender, peppermint, rose, clary sage, tea tree, eucalyptus, and citrus; however, there are approximately 300 EOs available.² EOs are used most often via topical application, inhalation, or ingestion.

As with any botanical agent, EOs are complex substances often containing a multitude of chemical compounds.¹ Because of the complex makeup of EOs, which often contain up to 100 volatile organic compounds, and their wide-ranging potential effects, applying the scientific method to study effectiveness poses a challenge that has limited their adoption in evidence-based practice.²

Availability and cost. EOs can be purchased at large retailers (eg, grocery stores, drug stores) and smaller health food stores, as well as on the Internet. Various EO vehicles, such as inhalers and topical creams, also can be purchased at these stores.

Continue to: The cost varies...

The cost varies enormously by manufacturer and type of plant used to make the EO. Common EOs such as peppermint and lavender oil generally cost $10 to $25, while rarer plant oils can cost $80 or more per bottle.

How safe are essential oils?

Patients may assume EOs are harmless because they are derived from natural plants and have been used medicinally for centuries. However, care must be taken with their use.

The safest way to use EOs is topically, although due to their highly concentrated nature, EOs should be diluted in an unscented neutral carrier oil such as coconut, jojoba, olive, or sweet almond.³ Ingestion of certain oils can cause hepatotoxicity, seizures, and even death.³ In fact, patients should speak with a knowledgeable physician before purchasing any oral EO capsules.

Whether used topically or ingested, all EOs carry risk for skin irritation and allergic reactions, and oral ingestion may result in some negative gastrointestinal (GI) adverse effects.⁴ A case report of 3 patients published in 2007 identified the potential for lavender and tea tree EOs to be endocrine disruptors.⁵

Inhalation of EOs may be harmful, as they emit many volatile organic compounds, some of which are considered potentially hazardous.⁶ At this time, there is insufficient evidence regarding inhaled EOs and their direct connection to respiratory health. It is reasonable to suggest, however, that the prolonged use of EOs and their use by patients who have lung conditions such as asthma or COPD should be avoided.⁷

Continue to: How are quality and purity assessed?

How are quality and purity assessed?

Like other dietary supplements, EOs are not regulated. No US regulatory agencies (eg, the US Food and Drug Administration [FDA] or Department of Agriculture [USDA]) certify or approve EOs for quality and purity. Bottles labeled with “QAI” for Quality Assurance International or “USDA Organic” will ensure the plant constituents used in the EO are from organic farming but do not attest to quality or purity.

Essential oils are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for adjunctive treatment of migraine and tension-type headaches.

Manufacturers commonly use marketing terms such as “therapeutic grade” or “pure” to sell products, but again, these terms do not reflect the product’s quality or purity. A labeled single EO may contain contaminants, alcohol, or additional ingredients.⁷ When choosing to use EOs, identifying reputable brands is essential; one resource is the independent testing organization ConsumerLab.com.

It is important to assess the manufacturer and read ingredient labels before purchasing an EO to understand what the product contains. Reputable companies will identify the plant ingredient, usually by the formal Latin binomial name, and explain the extraction process. A more certain way to assess the quality and purity of an EO is to ask the manufacturer to provide a certificate of analysis and gas chromatography/mass spectroscopy (GC/MS) data for the specific product. Some manufacturers offer GC/MS test results on their website Quality page.⁸ Others have detailed information on quality and testing, and GC/MS test reports can be obtained.⁹ Yet another manufacturer has test results on a product page matching reports to batch codes.¹⁰

Which conditions have evidence of benefit from essential oils?

EOs currently are being studied for treatment of many conditions—including pain, GI disorders, behavioral health disorders, and women’s health issues. The TABLE summarizes the conditions treated, outcomes, and practical applications of EOs.^11-44

Pain

Headache. As an adjunct to available medications and procedures for headache treatment, EOs are one of the nonpharmacologic modalities that patients and clinicians have at their disposal for both migraine and ­tension-type headaches. A systematic review of 19 randomized controlled trials (RCTs) examining the effects of herbal ingredients for the acute treatment or prophylaxis of migraines found certain topically applied or inhaled EOs, such as peppermint and chamomile, to be effective for migraine pain alleviation; however, topically applied rose oil was not effective.^11-13 Note: “topical application” in these studies implies application of the EO to ≥ 1 of the following areas: temples, forehead, behind ears, or above upper lip/below the nose.

Continue to: One RCT with 120 patients...

One RCT with 120 patients evaluated diluted intranasal peppermint oil and found that it reduced migraine intensity at similar rates to intranasal lidocaine.¹³ In this study, patients were randomized to receive one of the following: 4% lidocaine, 1.5% peppermint EO, or placebo. Two drops of the intranasal intervention were self-administered while the patient was in a supine position with their head suspended off the edge of the surface on which they were lying. They were instructed to stay in this position for at least 30 seconds after administration.

With regard to tension headache treatment, there is limited literature on the use of EOs. One study found that a preparation of peppermint oil applied topically to the temples and forehead of study participants resulted in significant analgesic effect.¹⁴

Fibromyalgia. Usual treatments for fibromyalgia include exercise, antidepressant and anticonvulsant medications, and stress management. Evidence also supports the use of inhaled and topically applied (with and without massage) lavender oil to improve symptoms.²⁶ Positive effects may be related to the anal­gesic, anti-­inflammatory, sleep-regulating,­ and anxiety­-reducing effects of the major volatile compounds contained in lavender oil.

In one RCT with 42 patients with fibromyalgia, the use of inhaled lavender oil was shown to increase the perception of well-­being (assessed on the validated SF-36 Health Survey Questionnaire) after 4 weeks.²⁷ In this study, the patient applied 3 drops of an oil mixture, comprising 1 mL lavender EO and 10 mL of fixed neutral base oil, to the wrist and inhaled for 10 minutes before going to bed.

The use of a topical oil blend labeled “Oil 24” (containing camphor, rosemary, eucalyptus, peppermint, aloe vera, and lemon/orange) also has been shown to be more effective than placebo in managing fibromyalgia symptoms. A randomized controlled pilot study of 153 participants found that regular application of Oil 24 improved scores on pain scales and the Fibromyalgia Impact Questionnaire.²⁸

Continue to: GI disorders

GI disorders

Irritable bowel syndrome. Peppermint oil relaxes GI smooth muscle, which has led to investigation of its use in irritable bowel ­syndrome (IBS) symptom amelioration.¹⁷ One meta-analysis including 12 RCTs with 835 patients with undifferentiated IBS found that orally ingested peppermint EO capsules reduced patient-reported symptoms of either abdominal pain or global symptoms.¹⁸

One study utilized the Total IBS Symptom Score to evaluate symptom reduction in patients with IBS-D (with diarrhea) and IBS-M (mixed) using 180-mg peppermint EO capsules ingested 3 times daily. There was a significant improvement in abdominal pain/discomfort, bloating/distension, pain at evacuation, and bowel urgency.¹⁹ A reduction in symptoms was observed after the first 24 hours of treatment and at the end of the 4-week treatment period.

In another study, among the 190 patients meeting Rome IV criteria for general (nonspecific) IBS who were treated with 182-mg peppermint EO capsules, no statistically significant reduction in overall symptom relief was found (based on outcome measures by the FDA and European Medicines Agency). However, in a secondary outcome analysis, peppermint oil produced greater improvements than placebo for the alleviation of abdominal pain, discomfort, and general IBS severity.²⁰

Chemotherapy-induced nausea and vomiting. Patients with cancer undergoing chemotherapy often explore integrative medicine approaches, including aromatherapy, to ameliorate adverse effects and improve quality of life.³⁸ A few small studies have shown potential for the use of inhaled ginger oil to reduce nausea and vomiting severity and improve health-related quality-of-life measures in these patients.

Evidence supports the use of inhaled and topically applied lavender oil to improve fibromyalgia symptoms.

For example, a study with 60 participants found that inhaling ginger EO for 10 minutes was beneficial for reducing both nausea and vomiting.³⁹ A single-blind, controlled, ­randomized crossover study of 60 patients with breast cancer receiving chemotherapy showed that ginger EO inhaled 3 times per day for 2 minutes at a time can decrease the severity of nausea but had no effect on vomiting. The same study showed that health-­related quality of life improved with the ginger oil treatment.⁴⁰

Continue to: Other EOs such as cardamom...

Other EOs such as cardamom and peppermint show promise as an adjunctive treatment for chemotherapy-induced nausea and vomiting as well.³⁸

Postoperative nausea. A 2013 randomized trial of 303 patients examined the use of ginger EO, a blend of EOs (including ginger, spearmint, peppermint, and cardamom), and isopropyl alcohol. Both the single EO and EO blend significantly reduced the symptom of nausea. The number of antiemetic medications requested by patients receiving an EO also was significantly reduced compared to those receiving saline.¹⁵

The use of EOs to reduce nausea after cardiac operations was reviewed in an RCT of 60 surgical candidates using 10% peppermint oil via nebulization for 10 minutes.¹⁶ This technique was effective in reducing nausea during cardiac postoperative periods. Although the evidence for the use of EOs for postoperative nausea is not robust, it may be a useful and generally safe approach for this common issue.

Behavioral health

Insomnia. EOs have been used as a treatment for insomnia traditionally and in complementary, alternative, and integrative medicine. A 2014 systematic review of 15 quantitative studies, including 11 RCTs, evaluated the hypnotic effects of EOs through inhalation, finding the strongest evidence for lavender, jasmine, and peppermint oils.²⁹ The majority of the studies in the systematic review used the Pittsburgh Sleep Quality Index (PSQI) to evaluate EO effectiveness. A more recent 2021 systematic review and meta-analysis that evaluated 34 RCTs found that inhalation of EOs, most notably lavender aromatherapy, is effective in improving sleep problems such as insomnia.³⁰

Findings from multiple smaller RCTs were consistent with those of the aforementioned systematic reviews. For example, in a well-conducted parallel randomized double-blind placebo-controlled trial of 100 people using orally ingested lemon verbena, the authors concluded that this intervention can be a complementary therapy for improving sleep quality and reducing insomnia severity.³¹ Another RCT with 60 participants evaluated an inhaled EO blend (lemon, eucalyptus, tea tree, and peppermint) over 4 weeks and found lowered perceived stress and depression as well as better sleep quality, but no influence on objective physiologic data such as stress indices or immune states.³²

Continue to: In a 2020 randomized crossover...

In a 2020 randomized crossover placebo­controlled trial of 37 participants with diabetes reporting insomnia, inhaled lavender improved sleep quality and quantity, quality of life, and mood but not physiologic or metabolic measures, such as fasting glucose.³³ Findings were similar in a cohort of cardiac rehabilitation patients (n = 37) who were treated with either an inhaled combination of lavender, bergamot, and ylang ylang, or placebo; cotton balls infused with the intervention oil or placebo oil were placed at the patient’s bedside for 5 nights. Sleep quality of participants receiving intervention oil was significantly better than the sleep quality of participants receiving the placebo oil as measured by participant completion of the PSQI.³⁴

Anxiety is a common disorder that can be managed with nonpharmacologic treatments such as yoga, deep breathing, meditation, and EO therapy.^21,22 In a systematic review and meta-analysis, the inhaled and topical use (with or without massage) of lavender EO was shown to improve psychological and physical manifestations of anxiety.²³ Lavender EO is purported to affect the parasympathetic nervous system via anxiolytic, sedative, analgesic, and anticonvulsant properties.²⁴ One systematic review and meta-analysis evaluating the anxiolytic effect of both inhaled and topical lavender EO found improvement in several biomarkers and physiologic data including blood pressure, heart rate, and cortisol levels, as well as a reduction in self-reported levels of anxiety, compared with placebo.²⁵

Anxiety related to dental procedures is another area of study for the use of EOs. Two RCTs demonstrate statistically significant improvement in anxiety-related physiologic markers such as heart rate, blood pressure, and salivary cortisol levels in children who inhaled lavender EO during dental procedures.^41,42 In 1 of the RCTs, the intervention was described as 3 drops of 100% lavender EO applied to a cloth and inhaled over the course of 3 minutes.⁴¹ Additionally, 2 studies found that orange EO was beneficial for dental procedure–induced anxiety, reducing pulse rates, cortisol levels, and self-reported anxiety.^43,44

Dementia-related behavioral disturbances. A small, poorly designed study examining 2 EO blends—rosemary with lemon and lavender with orange—found some potential for improving cognitive function, especially in patients with Alzheimer disease.⁴⁵ A Cochrane review of 13 RCTs totaling 708 patients concluded that it is not certain from the available evidence that EO therapy benefits patients with dementia in long-term-care facilities and hospital wards.⁴⁶ Given that reporting of adverse events in the trials was poor, it is not possible to make conclusions about the risk vs benefit of EO therapy in this population.

Women’s health

Dysmenorrhea. Interest has grown in the use of EOs for dysmenorrhea symptom relief, and there is a small body of evidence demonstrating that a variety of oils—most notably lavender, rose, and clary sage—may reduce symptom severity. One meta-analysis of 9 RCTs and 12 controlled clinical trials including women with moderate-to-severe dysmenorrhea found that inhaled and/or topical use of singular or mixed lavender, clary sage, rose, marjoram, and cinnamon EOs demonstrated the strongest evidence of effectiveness in reducing menstrual cramping.³⁵

Continue to: In a randomized, double-blind clinical trial...

Use of an inhaled blend of lemon, eucalyptus, tea tree, and peppermint was associated with lower perceived stress and depression as well as better sleep quality.

In a randomized, double-blind clinical trial of 48 women, a cream-based blend of lavender, clary sage, and marjoram EO (used topically in a 2:1:1 ratio diluted in unscented cream at 3% concentration and applied daily via abdominal massage) reduced participants’ reported menstrual pain symptoms and duration of pain.³⁶ In a meta-analysis of 6 studies, topical abdominal application of EO (mainly lavender with or without other oils) with massage showed superiority over massage with placebo oils in reducing menstrual pain.³⁷ A reduction in pain, mood symptoms, and fatigue in women with premenstrual symptoms was seen in an RCT of 77 patients using 3 drops of inhaled lavender EO.⁴⁷

Labor. There is limited evidence for the use of EOs during labor. In an RCT of 104 women, patient-selected diffused EOs, including lavender, rose geranium, citrus, or jasmine, were found to help lower pain scores during the latent and early active phase of labor. There were no differences in labor augmentation, length of labor, perinatal outcomes, or need for additional pain medication.⁴⁸

Other uses

Antimicrobial support. Some common EOs that have demonstrated antimicrobial properties are oregano, thyme, clove, lavender, clary sage, garlic, and cinnamon.^49,50 Topical lemongrass and tea tree EOs have shown some degree of efficacy as an alternative treatment for acne, decolonization of methicillin-resistant Staphylococcus aureus, and superficial fungal infections.⁵¹ Support for an oral mixture of EOs labeled Myrtol (containing eucalyptus, citrus myrtle, and lavender) for viral acute bronchitis and sinusitis was found in a review of 7 studies.⁵² More research needs to be done before clear recommendations can be made on the use of EOs as antimicrobials, but the current data are encouraging.

Insect repellent. Reviews of the ­insect-repellent properties of EOs have shown promise and are in the public’s interest due to increasing awareness of the potential health and environmental hazards of synthetic repellents.⁵³ Individual compounds present in EOs such as citronella/lemongrass, basil, and eucalyptus species demonstrate high repellent activity.⁵⁴ Since EOs require frequent reapplication for efficacy due to their highly volatile nature, scientists are currently developing a means to prolong their protection time through cream-based formulations.⁵⁵

The bottom line

Because of the ubiquity of EOs, family physicians will undoubtedly be asked about them by patients, and it would be beneficial to feel comfortable discussing their most common uses. For most adult patients, the topical and periodic inhaled usage of EOs is generally safe.⁵⁶

There is a small body of evidence demonstrating that a variety of essential oils, most notably lavender, rose, and clary sage, may reduce dysmenorrhea symptom severity.

There is existing evidence of efficacy for a number of EOs, most strongly for lavender and peppermint. Future research into EOs should include higher-powered and higher-­quality studies in order to provide more conclusive evidence regarding the continued use of EOs for many common conditions. More evidence-based information on dosing, application/use regimens, and safety in long-term use also will help providers better instruct patients on how to utilize EOs effectively and safely. 

CORRESPONDENCE
Pooja Amy Shah, MD, Columbia University College of Physicians & Surgeons, 610 West 158th Street, New York, NY 10032; [email protected]

Prior authorization requirements delay or preclude recommended treatment in a substantial proportion of oncology patients, findings from a survey-based cross-sectional study suggest.

Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.

Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.

Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.

The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.

“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”

To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.

PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).

“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.

PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.

Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.

The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.

“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.

“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.

Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.

Prior authorization requirements delay or preclude recommended treatment in a substantial proportion of oncology patients, findings from a survey-based cross-sectional study suggest.

Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.

Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.

Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.

The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.

“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”

To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.

PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).

“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.

PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.

Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.

The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.

“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.

“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.

Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.

Prior authorization requirements delay or preclude recommended treatment in a substantial proportion of oncology patients, findings from a survey-based cross-sectional study suggest.

Of 178 respondents with a prior authorization (PA) experience, 39 (22%) did not receive the care recommended by their treatment team because of a PA requirement, and 123 (69%) experienced a delay in receiving the recommended care, Fumiko Chino, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported.

Reasons for not receiving recommended care included complete denial by the insurance company (26 of 39 patients), and a change in treatment plan because of initial denial (13 of 39 patients). Delays in receiving recommended care were 2 or more weeks for 90 of 123 patients, and 1 month or more in 40 of 123 patients.

Delays in receiving recommended care were associated with increased patient anxiety, a negative perception of the PA process, and patient administrative burden, the investigators noted.

The findings, which capture patient-based perspectives in the ongoing PA debacle, were reported online in JAMA Network Open.

“Prior authorization requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denial can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management,” the investigators explained. “Focusing on patient experiences with PA highlights a missing perspective in policy discussions and suggests another potential factor associated with eroding trust in the health care system.”

To assess the impact of PA, they conducted an anonymous survey using a convenience sample of patients with any cancer-related PA experience from July 1 to Oct. 6, 2022. Mean self-reported PA-related anxiety scores were 74.7 on a scale of 0-100, whereas usual anxiety scores were 37.5.

PA-related anxiety scores were significantly correlated with the length of treatment delay (P = .04), time spent on PA (P < .001), and overall PA experience (P < .001).

“Dealing with PA issues adds an extra layer of stress, which is known to increase anxiety and can worsen treatment-related and disease-related symptoms and adverse effects,” the investigators noted.

PA issues also eroded trust: 89% of respondents trusted their insurance company less, and 83% trusted the health care system less after a PA experience. Patient involvement in the PA process increased the likelihood of such distrust and of having a negative experience.

Of the 178 respondents, most were women (88%), non-Hispanic White individuals (84%), college graduates (84%), and young (18-39 years, 41%; 40-54 years, 33%). Most (67%) had to personally become involved in the PA process by calling their insurance or filing an appeal.

The investigators noted that “efforts to create national health policy solutions that streamline PA and make the process more transparent have been a major lobbying effort of large oncology societies,” and that bipartisan legislation to “establish regulations on the quality and timeliness of PA in the Medicare Advantage population” has stalled.

“In the meantime, the Centers for Medicare & Medicaid Services acted directly by issuing a final rule in April 2023 aimed at improving PA processes within the Medicare Advantage population by 2024,” they wrote, adding that “streamlining the PA process is key to optimizing the quality of care delivered and improving patients’ experience with cancer care.

“Policy interventions will be necessary to reform the PA process, as will advocacy efforts at the patient, clinician, and hospital level,” they concluded.

Chino reported funding through a National Institutes of Health/National Cancer Institute Cancer Center Support Grant.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Hearing loss and tinnitus are the top and third most common service-connected disabilities among veterans. According to a Veterans Benefits Administration report, as of fiscal year 2020, more than 1.3 million veterans were receiving disability compensation for hearing loss and more than 2.3 million for tinnitus. Not surprisingly, the US Department of Veterans Affairs (VA) is the largest employer of audiologists and speech-language pathologists in the US.

On the bright side, military hearing losses are at stable levels—but “it’s not improving,” said US Army Lt Col Michael Murphy, chief of the studies and analysis section and Army audiology liaison at the Defense Health Agency Hearing Center of Excellence (HCE), in an interview for Department of Defense news.

Hearing protection is critical to reduce injury. Exposure to firearms, explosives, and other “continuous hazardous noise” puts service members and US Department of Defense (DoD) civilians at risk of permanent hearing loss, said Theresa Schulz, PhD, chief of the HCE prevention and surveillance section. “Good hearing is a key to mission success.”

Hearing protectors, which Shulz calls “the last line of defense from noise-induced hearing loss,” work best when they fit right: protecting against noise and, when necessary, not muffling voices, alarms, and other important sounds. That is why the DoD has updated its requirements for fit testing. All DoD personnel who are exposed to continuous and intermittent noise ≥ 85 decibels (in an 8-hour average) or impulse noise sound pressure ≥ 140 decibels (for ≥ 1 day per year) must be enrolled in a hearing conservation program. Additional criteria are expected for release by December 2023. According to HCE, each service may have more stringent requirements for hearing protector fit testing that better meets the needs of their hearing conservation program.

The question of proper fit was at the root of a recent lawsuit charging 3M with knowingly selling defective earplugs to the US military. The 3M dual-ended Combat Arms Earplug (CAEv2) was designed to eliminate the need for soldiers to carry 2 different sets of earplugs. Worn one way, it was intended to block sound like traditional earplugs; worn in reverse, it would block only certain types of loud battlefield noise while allowing the wearer to hear softer, closer sounds.

However, no 2 ears are the same—even on the same person. According to the HCE, during hearing protection testing, there is a < 2 mm difference in insertion depth between left and right ears for 85% of subjects. A 2016 whistleblower lawsuit accused 3M of not disclosing that the CAEv2 was too short for proper insertion into users’ ears and that it could loosen imperceptibly and fail to form the protective seal.

In 2018, 3M agreed to pay $9.1 million to the Department of Justice to resolve the allegations without admitting liability. That case led to the largest mass tort multidistrict litigation in US history. Last February, Veterans of Foreign Wars (VFW) filed an amicus curiae brief to the Seventh Circuit Court of Appeals in support of claimants seeking relief from 3M for defective ear protection. Approximately 240,000 veterans filed lawsuits against 3M. In September the parties reached a $6 billion settlement—nearly half of 3M’s worth. According to John Muckelbauer, a veteran and general counsel for the VFW in a military.com opinion piece, the settlement achieves balance: not pushing the already financially strapped 3M into bankruptcy, but sending “a strong signal that the safety of our service members can never be compromised.”

Crucially, Muckelbauer notes, the VA says participating in the lawsuit will not result in the loss of health or disability benefits, nor will it adversely affect disability ratings. VA facilities are also barred from recovering any portion of a plaintiff’s award as part of a medical lien.

3M has not admitted responsibility in this settlement either, frustrating the veteran claimants. An admission of guilt was never on the table, says Ronald Miller, Jr., writing for the Lawsuit Information Center, which posts updates on class action lawsuits. “Admitting responsibility would open the door for everyone to opt out and move forward on that admission… Admitting guilt would also be harmful to 3M’s reputation. They have long vigorously denied responsibility, so the optics would be terrible.”

A new twist cropped up almost immediately when claimants began getting cold calls from scammers impersonating employees of Archer Systems LLC, the company designated to administer the settlement. The scammers attempted to extract sensitive personal information, including Social Security numbers. Judge M. Casey Rodgers alerted the Federal Bureau of Investigation and warned claimants to safeguard their data vigilantly and report any fraudulent attempts.

The settlement money will be paid out from 2023 to 2029, with $1 billion in the form of 3M stock, 3M said in a statement. (In August 2023, upon news of the settlement, the price of 3M shares had risen nearly 5%.) Miller says the whole $6 billion will be distributed using a point system that awards amounts according to disability, with, for instance, tinnitus without contemporaneous corroboration getting the least and moderate or greater hearing loss getting the most. “This settlement is a tremendous outcome for veterans of Iraq and Afghanistan who put their lives on the line for our freedom,” said Duane Sarmiento, VFW national commander in a statement. “For those who came home with hearing damage due to 3M’s faulty earplugs, this is not only compensation, it’s a statement that their sacrifices won’t be ignored.”

Hearing loss and tinnitus are the top and third most common service-connected disabilities among veterans. According to a Veterans Benefits Administration report, as of fiscal year 2020, more than 1.3 million veterans were receiving disability compensation for hearing loss and more than 2.3 million for tinnitus. Not surprisingly, the US Department of Veterans Affairs (VA) is the largest employer of audiologists and speech-language pathologists in the US.

On the bright side, military hearing losses are at stable levels—but “it’s not improving,” said US Army Lt Col Michael Murphy, chief of the studies and analysis section and Army audiology liaison at the Defense Health Agency Hearing Center of Excellence (HCE), in an interview for Department of Defense news.

Hearing protection is critical to reduce injury. Exposure to firearms, explosives, and other “continuous hazardous noise” puts service members and US Department of Defense (DoD) civilians at risk of permanent hearing loss, said Theresa Schulz, PhD, chief of the HCE prevention and surveillance section. “Good hearing is a key to mission success.”

Hearing protectors, which Shulz calls “the last line of defense from noise-induced hearing loss,” work best when they fit right: protecting against noise and, when necessary, not muffling voices, alarms, and other important sounds. That is why the DoD has updated its requirements for fit testing. All DoD personnel who are exposed to continuous and intermittent noise ≥ 85 decibels (in an 8-hour average) or impulse noise sound pressure ≥ 140 decibels (for ≥ 1 day per year) must be enrolled in a hearing conservation program. Additional criteria are expected for release by December 2023. According to HCE, each service may have more stringent requirements for hearing protector fit testing that better meets the needs of their hearing conservation program.

The question of proper fit was at the root of a recent lawsuit charging 3M with knowingly selling defective earplugs to the US military. The 3M dual-ended Combat Arms Earplug (CAEv2) was designed to eliminate the need for soldiers to carry 2 different sets of earplugs. Worn one way, it was intended to block sound like traditional earplugs; worn in reverse, it would block only certain types of loud battlefield noise while allowing the wearer to hear softer, closer sounds.

However, no 2 ears are the same—even on the same person. According to the HCE, during hearing protection testing, there is a < 2 mm difference in insertion depth between left and right ears for 85% of subjects. A 2016 whistleblower lawsuit accused 3M of not disclosing that the CAEv2 was too short for proper insertion into users’ ears and that it could loosen imperceptibly and fail to form the protective seal.

In 2018, 3M agreed to pay $9.1 million to the Department of Justice to resolve the allegations without admitting liability. That case led to the largest mass tort multidistrict litigation in US history. Last February, Veterans of Foreign Wars (VFW) filed an amicus curiae brief to the Seventh Circuit Court of Appeals in support of claimants seeking relief from 3M for defective ear protection. Approximately 240,000 veterans filed lawsuits against 3M. In September the parties reached a $6 billion settlement—nearly half of 3M’s worth. According to John Muckelbauer, a veteran and general counsel for the VFW in a military.com opinion piece, the settlement achieves balance: not pushing the already financially strapped 3M into bankruptcy, but sending “a strong signal that the safety of our service members can never be compromised.”

Crucially, Muckelbauer notes, the VA says participating in the lawsuit will not result in the loss of health or disability benefits, nor will it adversely affect disability ratings. VA facilities are also barred from recovering any portion of a plaintiff’s award as part of a medical lien.

3M has not admitted responsibility in this settlement either, frustrating the veteran claimants. An admission of guilt was never on the table, says Ronald Miller, Jr., writing for the Lawsuit Information Center, which posts updates on class action lawsuits. “Admitting responsibility would open the door for everyone to opt out and move forward on that admission… Admitting guilt would also be harmful to 3M’s reputation. They have long vigorously denied responsibility, so the optics would be terrible.”

A new twist cropped up almost immediately when claimants began getting cold calls from scammers impersonating employees of Archer Systems LLC, the company designated to administer the settlement. The scammers attempted to extract sensitive personal information, including Social Security numbers. Judge M. Casey Rodgers alerted the Federal Bureau of Investigation and warned claimants to safeguard their data vigilantly and report any fraudulent attempts.

The settlement money will be paid out from 2023 to 2029, with $1 billion in the form of 3M stock, 3M said in a statement. (In August 2023, upon news of the settlement, the price of 3M shares had risen nearly 5%.) Miller says the whole $6 billion will be distributed using a point system that awards amounts according to disability, with, for instance, tinnitus without contemporaneous corroboration getting the least and moderate or greater hearing loss getting the most. “This settlement is a tremendous outcome for veterans of Iraq and Afghanistan who put their lives on the line for our freedom,” said Duane Sarmiento, VFW national commander in a statement. “For those who came home with hearing damage due to 3M’s faulty earplugs, this is not only compensation, it’s a statement that their sacrifices won’t be ignored.”

Hearing loss and tinnitus are the top and third most common service-connected disabilities among veterans. According to a Veterans Benefits Administration report, as of fiscal year 2020, more than 1.3 million veterans were receiving disability compensation for hearing loss and more than 2.3 million for tinnitus. Not surprisingly, the US Department of Veterans Affairs (VA) is the largest employer of audiologists and speech-language pathologists in the US.

On the bright side, military hearing losses are at stable levels—but “it’s not improving,” said US Army Lt Col Michael Murphy, chief of the studies and analysis section and Army audiology liaison at the Defense Health Agency Hearing Center of Excellence (HCE), in an interview for Department of Defense news.

Hearing protection is critical to reduce injury. Exposure to firearms, explosives, and other “continuous hazardous noise” puts service members and US Department of Defense (DoD) civilians at risk of permanent hearing loss, said Theresa Schulz, PhD, chief of the HCE prevention and surveillance section. “Good hearing is a key to mission success.”

Hearing protectors, which Shulz calls “the last line of defense from noise-induced hearing loss,” work best when they fit right: protecting against noise and, when necessary, not muffling voices, alarms, and other important sounds. That is why the DoD has updated its requirements for fit testing. All DoD personnel who are exposed to continuous and intermittent noise ≥ 85 decibels (in an 8-hour average) or impulse noise sound pressure ≥ 140 decibels (for ≥ 1 day per year) must be enrolled in a hearing conservation program. Additional criteria are expected for release by December 2023. According to HCE, each service may have more stringent requirements for hearing protector fit testing that better meets the needs of their hearing conservation program.

The question of proper fit was at the root of a recent lawsuit charging 3M with knowingly selling defective earplugs to the US military. The 3M dual-ended Combat Arms Earplug (CAEv2) was designed to eliminate the need for soldiers to carry 2 different sets of earplugs. Worn one way, it was intended to block sound like traditional earplugs; worn in reverse, it would block only certain types of loud battlefield noise while allowing the wearer to hear softer, closer sounds.

However, no 2 ears are the same—even on the same person. According to the HCE, during hearing protection testing, there is a < 2 mm difference in insertion depth between left and right ears for 85% of subjects. A 2016 whistleblower lawsuit accused 3M of not disclosing that the CAEv2 was too short for proper insertion into users’ ears and that it could loosen imperceptibly and fail to form the protective seal.

In 2018, 3M agreed to pay $9.1 million to the Department of Justice to resolve the allegations without admitting liability. That case led to the largest mass tort multidistrict litigation in US history. Last February, Veterans of Foreign Wars (VFW) filed an amicus curiae brief to the Seventh Circuit Court of Appeals in support of claimants seeking relief from 3M for defective ear protection. Approximately 240,000 veterans filed lawsuits against 3M. In September the parties reached a $6 billion settlement—nearly half of 3M’s worth. According to John Muckelbauer, a veteran and general counsel for the VFW in a military.com opinion piece, the settlement achieves balance: not pushing the already financially strapped 3M into bankruptcy, but sending “a strong signal that the safety of our service members can never be compromised.”

Crucially, Muckelbauer notes, the VA says participating in the lawsuit will not result in the loss of health or disability benefits, nor will it adversely affect disability ratings. VA facilities are also barred from recovering any portion of a plaintiff’s award as part of a medical lien.

3M has not admitted responsibility in this settlement either, frustrating the veteran claimants. An admission of guilt was never on the table, says Ronald Miller, Jr., writing for the Lawsuit Information Center, which posts updates on class action lawsuits. “Admitting responsibility would open the door for everyone to opt out and move forward on that admission… Admitting guilt would also be harmful to 3M’s reputation. They have long vigorously denied responsibility, so the optics would be terrible.”

A new twist cropped up almost immediately when claimants began getting cold calls from scammers impersonating employees of Archer Systems LLC, the company designated to administer the settlement. The scammers attempted to extract sensitive personal information, including Social Security numbers. Judge M. Casey Rodgers alerted the Federal Bureau of Investigation and warned claimants to safeguard their data vigilantly and report any fraudulent attempts.

The settlement money will be paid out from 2023 to 2029, with $1 billion in the form of 3M stock, 3M said in a statement. (In August 2023, upon news of the settlement, the price of 3M shares had risen nearly 5%.) Miller says the whole $6 billion will be distributed using a point system that awards amounts according to disability, with, for instance, tinnitus without contemporaneous corroboration getting the least and moderate or greater hearing loss getting the most. “This settlement is a tremendous outcome for veterans of Iraq and Afghanistan who put their lives on the line for our freedom,” said Duane Sarmiento, VFW national commander in a statement. “For those who came home with hearing damage due to 3M’s faulty earplugs, this is not only compensation, it’s a statement that their sacrifices won’t be ignored.”