TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

Individuals spend close to half of their lives preventing, or planning for, pregnancy. As such, contraception plays a major role in patient-provider interactions. Contraception counseling and management is a common scenario encountered in the general gynecologist’s practice. Luckily, we have two evidence-based guidelines developed by the US Centers for Disease Control and Prevention (CDC) that support the provision of contraceptive care:

1. US Medical Eligibility for Contraceptive Use (US-MEC),¹ which provides guidance on which patients can safely use a method
2. US Selected Practice Recommendations for Contraceptive Use (US-SPR),² which provides method-specific guidance on how to use a method (including how to: initiate or start a method; manage adherence issues, such as a missed pill, etc; and manage common issues like breakthrough bleeding). Both of these guidelines are updated routinely and are publicly available online or for free, through smartphone applications.

While most contraceptive care is straightforward, there are circumstances that require additional consideration. In this 3-part series we review 3 clinical cases, existing evidence to guide management decisions, and our recommendations. In part 1, we focus on restarting hormonal contraception after ulipristal acetate administration. In parts 2 and 3, we will discuss removal of a nonpalpable contraceptive implant and the consideration of a levonorgestrel-releasing intrauterine device (LNG-IUD) for emergency contraception.

CASE Meeting emergency and follow-up contraception needs

A 27-year-old woman (G0) presents to you after having unprotected intercourse 4 days ago. She does not formally track her menstrual cycles and is unsure when her last menstrual period was. She is not using contraception but is interested in starting a method. After counseling, she elects to take a dose of oral ulipristal acetate (UPA; Ella) now for emergency contraception and would like to start a combined oral contraceptive (COC) pill moving forward.

How soon after taking UPA should you tell her to start the combined hormonal pill?

Effectiveness of hormonal contraception following UPA

UPA does not appear to decrease the efficacy of COCs when started around the same time. However, immediately starting a hormonal contraceptive can decrease the effectiveness of UPA, and as such, it is recommended to take UPA and then abstain or use a backup method for 7 days before initiating a hormonal contraceptive method.¹ By obtaining some additional information from your patient and with the use of shared decision making, though, your patient may be able to start their contraceptive method earlier than 5 days after UPA.

What is UPA

UPA is a progesterone receptor modulator used for emergency contraception intenhded to prevent pregnancy after unprotected intercourse or contraceptive failure.³ It works by delaying follicular rupture at least 5 days, if taken before the peak of the luteinizing hormone (LH) surge. If taken after that timeframe, it does not work. Since UPA competes for the progesterone receptor, there is a concern that the effectiveness of UPA may be decreased if a progestin-containing form of contraception is started immediately after taking UPA, or vice versa.⁴ Several studies have now specifically looked at the interaction between UPA and progestin-containing contraceptives, including at how UPA is impacted by the contraceptive method, and conversely, how the contraceptive method is impacted by UPA.^5-8

Data on types of hormonal contraception. Brache and colleagues demonstrated that UPA users who started a desogestrel progestin-only pill (DSG POP) the next day had higher rates of ovulation within 5 days of taking UPA (45%), compared with those who the next day started a placebo pill (3%).⁶ This type of progestin-only pill is not available in the United States.

A study by Edelman and colleagues demonstrated similar findings in those starting a COC pill containing estrogen and progestin. When taking a COC two days after UPA use, more participants had evidence of follicular rupture in less than 5 days.⁵ It should be noted that these studies focused on ovulation, which—while necessary for conception to occur—is a surrogate biomarker for pregnancy risk. Additional studies have looked at the impact of UPA on the COC and have not found that UPA impacts ovulation suppression of the COC with its initiation or use.⁸

Considering unprotected intercourse and UPA timing. Of course, the risk of pregnancy is reliant on cycle timing plus the presence of viable sperm in the reproductive tract. Sperm have been shown to only be viable in the reproductive tract for 5 days, which could result in fertilization and subsequent pregnancy. Longevity of an egg is much shorter, at 12 to 24 hours after ovulation. For this patient, her exposure was 4 days ago, but sperm are only viable for approximately 5 days—she could consider taking the UPA now and then starting a COC earlier than 5 days since she only needs an extra day or two of protection from the UPA from the sperm in her reproductive tract. Your patient’s involvement in this decision making is paramount, as only they can prioritize their desire to avoid pregnancy from their recent act of unprotected intercourse versus their immediate needs for starting their method of contraception. It is important that individuals abstain from sexual activity or use an additional back-up method during the first 7 days of starting their method of contraception.

Continue to: Counseling considerations for the case patient...

For a patient planning to start or resume a hormonal contraceptive method after taking UPA, the waiting period recommended by the CDC (5 days) is most beneficial for patients who are uncertain about their menstrual cycle timing in relation to the act of unprotected intercourse that already occurred and need to prioritize maximum effectiveness of emergency contraception.

Patients with unsure cycle-sex timing planning to self-start or resume a short-term hormonal contraceptive method (eg, pills, patches, or rings), should be counseled to wait 5 days after the most recent act of unprotected sex, before taking their hormonal contraceptive method.⁷ Patients with unsure cycle-sex timing planning to use provider-dependent hormonal contraceptive methods (eg, those requiring a prescription, including a progestin-contraceptive implant or depot medroxyprogesterone acetate) should also be counseled to wait. Timing of levonorgestrel and copper intrauterine devices are addressed in part 3 of this series.

However, if your patient has a good understanding of their menstrual cycle, and the primary concern is exposure from subsequent sexual encounters and not the recent unprotected intercourse, it is advisable to provide UPA and immediately initiate a contraceptive method. One of the primary reasons for emergency contraception failure is that its effectiveness is limited to the most recent act of unprotected sexual intercourse and does not extend to subsequent acts throughout the month.

For these patients with sure cycle-sex timing who are planning to start or resume short-or long-term contraceptive methods, and whose primary concern is to prevent pregnancy risk from subsequent sexual encounters, immediately initiating a contraceptive method is advisable. For provider-dependent methods, we must weigh the risk of unintended pregnancy from the act of intercourse that already occurred (and the potential to increase that risk by initiating a method that could compromise UPA efficacy) versus the future risk of pregnancy if the patient cannot return for a contraception visit.⁷

In short, starting the contraceptive method at the time of UPA use can be considered after shared decision making with the patient and understanding what their primary concerns are.

Important point

Counsel on using backup barrier contraception after UPA

Oral emergency contraception only covers that one act of unprotected intercourse and does not continue to protect a patient from pregnancy for the rest of their cycle. When taken before ovulation, UPA works by delaying follicular development and rupture for at least 5 days. Patients who continue to have unprotected intercourse after taking UPA are at a high risk of an unintended pregnancy from this ‘stalled’ follicle that will eventually ovulate. Follicular maturation resumes after UPA’s effects wane, and the patient is primed for ovulation (and therefore unintended pregnancy) if ongoing unprotected intercourse occurs for the rest of their cycle.

Therefore, it is important to counsel patients on the need, if they do not desire a pregnancy, to abstain or start a method of contraception.

Final question

What about starting or resuming non–hormonal contraceptive methods?

Non-hormonal contraceptive methods can be started immediately with UPA use.¹

CASE Resolved

After shared decision making, the patient decides to start using the COC pill. You prescribe her both UPA for emergency contraception and a combined hormonal contraceptive pill. Given her unsure cycle-sex timing, she expresses to you that her most important priority is preventing unintended pregnancy. You counsel her to set a reminder on her phone to start taking the pill 5 days from her most recent act of unprotected intercourse. You also counsel her to use a back-up barrier method of contraception for 7 days after starting her COC pill. ●

CASE Pregnant woman asks about the RSV vaccine

A 28-year-old primigravid woman at 30 weeks’ gestation inquires about the new vaccine to protect her newborn baby against respiratory syncytial virus infection (RSV). Her neighbor’s daughter recently was hospitalized for the treatment of RSV, and she is understandably concerned about her own newborn. The patient is healthy, and she has never had any serious respiratory infection. She is taking no medications other than prenatal vitamins.

What advice should you give her? 

If you decide to administer this vaccine, what is the appropriate timing of administration?

Are there any maternal or fetal safety concerns related to use of this vaccine in pregnancy?
 

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family. It is an enveloped, single-stranded RNA virus that is 150-300 nm in size. The virus codes for 10 virus-specific proteins. The 2 most important are the G protein, which enables the virus to attach to host cells, and the F protein, which facilitates the entry of the virus into the host cell by fusing the host and viral membranes. Two distinct subtypes exist: A and B. There is genetic variation within each subtype and between subtypes. These subtle genetic variations create the potential for reinfections, and hence, research has focused on development of a vaccine that covers both subtypes.¹

RSV is the most common cause of acute lower respiratory tract infection in infants younger than 6 months of age. In these children, RSV is one of the most prominent causes of death, with mortality particularly marked in low- and middle-resource countries as well as in children who were born premature and/or who are immunocompromised. RSV has its greatest impact during winter epidemics in temperate climates and during the rainy seasons in tropical climates. The virus rarely is encountered in the summer.¹ Among young children, RSV primarily is transmitted via close contact with contaminated fingers or fomites and by self-inoculation of the conjunctiva or anterior nares. The incubation period of the infection is 4 to 6 days, and viral shedding may persist for 2 weeks or longer. Most patients gradually recover within 1 to 2 weeks.¹ Adults who contract RSV usually have symptoms suggestive of a common cold; however, in older adults or those who have comorbidities, serious and potentially life-threatening lower respiratory tract infections may develop.

Recently, there have been 2 main approaches to the prevention and treatment of RSV in infants. One has been the development of monoclonal antibodies such as motavizumab, palivizumab, and nirsevimab. The other has been the development of a vaccine that could be administered to pregnant women and which could provide protection for the neonate in the early months of life.^2,3

In late August 2023, the US Food and Drug Administration (FDA) announced the approval of a new bivalent RSV prefusion F vaccine (ABRYSVO, Pfizer) intended for administration to pregnant women.⁴ Of note, previous efforts to develop whole-virus vaccines either have been ineffective or have potentiated the disease in infants who became infected; development of an effective vaccine had eluded scientists and clinicians for nearly 50 years.² Thus, the new vaccine that targets the F protein of the virus represents a major and welcomed breakthrough.

This article reviews the 3 most recent investigations that preceded the ultimate approval of this vaccine and discusses specific logistical issues related to vaccine administration.

Continue to: First step toward vaccine approval...

First step toward vaccine approval

Madhi and colleagues⁵ were among the first to conduct a large well-designed study to evaluate the effectiveness of maternal vaccination in preventing neonatal infection in the first few months of life. The authors enrolled more than 4,500 healthy pregnant women at 28 to 36 weeks of gestation and assigned them to receive either a single intramuscular dose of an RSV fusion (F) protein vaccine or placebo in a ratio of 2:1. The primary end point was a “medically significant lower respiratory tract infection” within the first 90 days of life. The percentage of infants who met the primary end point was low in both groups: 1.5% in the vaccine group and 2.4% in the placebo group (efficacy 39.4%). The efficacy of the vaccine in preventing lower respiratory tract infection with severe hypoxemia was 48.3% and 44.4% in preventing hospitalization. Although there were differences between the 2 groups, they did not meet the prespecified success criterion for efficacy. Vaccine recipients had more local injection site reactions (40.7% vs 9.9%); however, there was no difference in the frequency of other adverse effects.

Intermediate step: Continued assessment of vaccine safety and immunogenicity

The next important step in the development of the RSV vaccine was a study by Simoes et al,⁶ who conducted a phase 2b trial to determine the safety and immunogenicity of the RSVpreF vaccine. The authors randomly assigned pregnant women at 24 to 36 weeks of gestation to receive either 120 or 240 µg of RSVpreF vaccine or placebo. The key endpoints were the following: maternal and infant safety; the maternal-to-infant transplacental transfer ratio; and the presence of RSV A, B, and combined A/B neutralizing antibody in maternal serum and umbilical cord blood at delivery. The authors conducted a planned interim analysis that included 327 mothers who received the vaccine. The incidence of adverse effects was similar in mothers and infants in the vaccine compared with the placebo group. None of the adverse effects were judged to be serious. The transplacental neutralizing antibody transfer ratios ranged from 1.4 to 2.1 across a range of gestational ages. The vaccine elicited meaningful neutralizing titers of antibody in maternal serum even up to 7 weeks after immunization. The levels of neutralizing antibodies in umbilical cord blood did not vary substantially with respect to gestational age. A post hoc analysis showed that the transferred antibodies prevented medically-attended RSV-associated lower respiratory tract illnesses in the infants.

Final step: Convincing proof of efficacy

The most recent of the 3 studies, and the one that had the greatest impact in convincing the FDA to approve the vaccine, was the report by Kampmann and colleagues.⁷ The authors conducted a phase 3 prospective, randomized, double-blind trial in 18 different countries over 4 RSV seasons: 2 in the northern hemisphere and 2 in the southern hemisphere. They enrolled healthy pregnant women with singleton gestations at 24 to 36 weeks of gestation and assigned them in a 1:1 ratio to a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. They excluded patients with any recognized risk factor for an adverse pregnancy outcome, including preterm labor. The 2 primary efficacy endpoints were a medically-attended severe RSV–lower respiratory tract infection and any medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.

The efficacy of the vaccine in preventing severe lower respiratory tract illness within 90 days of delivery was 81.8% (99.5% confidence interval [CI], 40.6–96.3). The efficacy within 180 days of delivery was 69.4% (97.58% CI, 44.3–84.1). These differences reached the study’s pre-established statistical criteria for success. The overall rate of lower respiratory tract infections was not significantly different. The frequencies of adverse effects in mothers and infants were similar in the vaccine and placebo groups. In particular, the frequency of preterm delivery in the vaccine group was 0.8%, compared with 0.6% in the placebo group (P = NS).

In previous reports to the FDA,⁴ the frequency rate of preterm delivery in RSV vaccine recipients was slightly increased in vaccine recipients compared with patients who received placebo. The difference among the groups was too small to infer a causal relationship; however, as a condition of vaccine approval, the FDA has required Pfizer to conduct a postmarketing study to be certain that administration of the vaccine does not increase the risk for preterm delivery.

Practical details

The new vaccine is a bivalent recombinant vaccine that elicits a robust antibody response against the F (fusion) protein of the virus. In addition to the F antigen, the vaccine contains the following buffer ingredients: tromethamine, sucrose, mannitol, polysorbate, and sodium chloride.⁸ There are no preservatives in the vaccine.

The vaccine should be administered in a single, 0.5 mL, intramuscular injection at 32 to 36 weeks of gestation. Patients who are allergic to any of the components of the vaccine should not be vaccinated. Patients with a mild upper respiratory tract infection may receive the vaccine. Administration should be delayed in patients who are moderately to severely ill. The vaccine may be administered at the same time as other vaccines, such as influenza or Tdap.

The most common side effects of the vaccine are local injection site reactions, such as pain, redness, or swelling. Some patients may experience mild systemic manifestations, including fatigue, fever, headache, nausea, diarrhea, arthralgias, and myalgias. According to the Centers for Disease Control and Prevention, the approximate wholesale acquisition cost of the vaccine is $320 for 1 injection.

CASE Resolution

This patient is healthy and has no contraindication to the new RSV vaccine. According to the FDA, the optimal time for administration of the vaccine is 32 to 36 weeks of gestation. The patient should anticipate very few side effects following the vaccination, and the vaccine has approximately 80% efficacy in preventing severe lower respiratory tract infection in her neonate. ●

CASE Pregnant woman asks about the RSV vaccine

A 28-year-old primigravid woman at 30 weeks’ gestation inquires about the new vaccine to protect her newborn baby against respiratory syncytial virus infection (RSV). Her neighbor’s daughter recently was hospitalized for the treatment of RSV, and she is understandably concerned about her own newborn. The patient is healthy, and she has never had any serious respiratory infection. She is taking no medications other than prenatal vitamins.

What advice should you give her? 

If you decide to administer this vaccine, what is the appropriate timing of administration?

Are there any maternal or fetal safety concerns related to use of this vaccine in pregnancy?
 

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family. It is an enveloped, single-stranded RNA virus that is 150-300 nm in size. The virus codes for 10 virus-specific proteins. The 2 most important are the G protein, which enables the virus to attach to host cells, and the F protein, which facilitates the entry of the virus into the host cell by fusing the host and viral membranes. Two distinct subtypes exist: A and B. There is genetic variation within each subtype and between subtypes. These subtle genetic variations create the potential for reinfections, and hence, research has focused on development of a vaccine that covers both subtypes.¹

RSV is the most common cause of acute lower respiratory tract infection in infants younger than 6 months of age. In these children, RSV is one of the most prominent causes of death, with mortality particularly marked in low- and middle-resource countries as well as in children who were born premature and/or who are immunocompromised. RSV has its greatest impact during winter epidemics in temperate climates and during the rainy seasons in tropical climates. The virus rarely is encountered in the summer.¹ Among young children, RSV primarily is transmitted via close contact with contaminated fingers or fomites and by self-inoculation of the conjunctiva or anterior nares. The incubation period of the infection is 4 to 6 days, and viral shedding may persist for 2 weeks or longer. Most patients gradually recover within 1 to 2 weeks.¹ Adults who contract RSV usually have symptoms suggestive of a common cold; however, in older adults or those who have comorbidities, serious and potentially life-threatening lower respiratory tract infections may develop.

Recently, there have been 2 main approaches to the prevention and treatment of RSV in infants. One has been the development of monoclonal antibodies such as motavizumab, palivizumab, and nirsevimab. The other has been the development of a vaccine that could be administered to pregnant women and which could provide protection for the neonate in the early months of life.^2,3

In late August 2023, the US Food and Drug Administration (FDA) announced the approval of a new bivalent RSV prefusion F vaccine (ABRYSVO, Pfizer) intended for administration to pregnant women.⁴ Of note, previous efforts to develop whole-virus vaccines either have been ineffective or have potentiated the disease in infants who became infected; development of an effective vaccine had eluded scientists and clinicians for nearly 50 years.² Thus, the new vaccine that targets the F protein of the virus represents a major and welcomed breakthrough.

This article reviews the 3 most recent investigations that preceded the ultimate approval of this vaccine and discusses specific logistical issues related to vaccine administration.

Continue to: First step toward vaccine approval...

First step toward vaccine approval

Madhi and colleagues⁵ were among the first to conduct a large well-designed study to evaluate the effectiveness of maternal vaccination in preventing neonatal infection in the first few months of life. The authors enrolled more than 4,500 healthy pregnant women at 28 to 36 weeks of gestation and assigned them to receive either a single intramuscular dose of an RSV fusion (F) protein vaccine or placebo in a ratio of 2:1. The primary end point was a “medically significant lower respiratory tract infection” within the first 90 days of life. The percentage of infants who met the primary end point was low in both groups: 1.5% in the vaccine group and 2.4% in the placebo group (efficacy 39.4%). The efficacy of the vaccine in preventing lower respiratory tract infection with severe hypoxemia was 48.3% and 44.4% in preventing hospitalization. Although there were differences between the 2 groups, they did not meet the prespecified success criterion for efficacy. Vaccine recipients had more local injection site reactions (40.7% vs 9.9%); however, there was no difference in the frequency of other adverse effects.

Intermediate step: Continued assessment of vaccine safety and immunogenicity

The next important step in the development of the RSV vaccine was a study by Simoes et al,⁶ who conducted a phase 2b trial to determine the safety and immunogenicity of the RSVpreF vaccine. The authors randomly assigned pregnant women at 24 to 36 weeks of gestation to receive either 120 or 240 µg of RSVpreF vaccine or placebo. The key endpoints were the following: maternal and infant safety; the maternal-to-infant transplacental transfer ratio; and the presence of RSV A, B, and combined A/B neutralizing antibody in maternal serum and umbilical cord blood at delivery. The authors conducted a planned interim analysis that included 327 mothers who received the vaccine. The incidence of adverse effects was similar in mothers and infants in the vaccine compared with the placebo group. None of the adverse effects were judged to be serious. The transplacental neutralizing antibody transfer ratios ranged from 1.4 to 2.1 across a range of gestational ages. The vaccine elicited meaningful neutralizing titers of antibody in maternal serum even up to 7 weeks after immunization. The levels of neutralizing antibodies in umbilical cord blood did not vary substantially with respect to gestational age. A post hoc analysis showed that the transferred antibodies prevented medically-attended RSV-associated lower respiratory tract illnesses in the infants.

Final step: Convincing proof of efficacy

The most recent of the 3 studies, and the one that had the greatest impact in convincing the FDA to approve the vaccine, was the report by Kampmann and colleagues.⁷ The authors conducted a phase 3 prospective, randomized, double-blind trial in 18 different countries over 4 RSV seasons: 2 in the northern hemisphere and 2 in the southern hemisphere. They enrolled healthy pregnant women with singleton gestations at 24 to 36 weeks of gestation and assigned them in a 1:1 ratio to a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. They excluded patients with any recognized risk factor for an adverse pregnancy outcome, including preterm labor. The 2 primary efficacy endpoints were a medically-attended severe RSV–lower respiratory tract infection and any medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.

The efficacy of the vaccine in preventing severe lower respiratory tract illness within 90 days of delivery was 81.8% (99.5% confidence interval [CI], 40.6–96.3). The efficacy within 180 days of delivery was 69.4% (97.58% CI, 44.3–84.1). These differences reached the study’s pre-established statistical criteria for success. The overall rate of lower respiratory tract infections was not significantly different. The frequencies of adverse effects in mothers and infants were similar in the vaccine and placebo groups. In particular, the frequency of preterm delivery in the vaccine group was 0.8%, compared with 0.6% in the placebo group (P = NS).

In previous reports to the FDA,⁴ the frequency rate of preterm delivery in RSV vaccine recipients was slightly increased in vaccine recipients compared with patients who received placebo. The difference among the groups was too small to infer a causal relationship; however, as a condition of vaccine approval, the FDA has required Pfizer to conduct a postmarketing study to be certain that administration of the vaccine does not increase the risk for preterm delivery.

Practical details

The new vaccine is a bivalent recombinant vaccine that elicits a robust antibody response against the F (fusion) protein of the virus. In addition to the F antigen, the vaccine contains the following buffer ingredients: tromethamine, sucrose, mannitol, polysorbate, and sodium chloride.⁸ There are no preservatives in the vaccine.

The vaccine should be administered in a single, 0.5 mL, intramuscular injection at 32 to 36 weeks of gestation. Patients who are allergic to any of the components of the vaccine should not be vaccinated. Patients with a mild upper respiratory tract infection may receive the vaccine. Administration should be delayed in patients who are moderately to severely ill. The vaccine may be administered at the same time as other vaccines, such as influenza or Tdap.

The most common side effects of the vaccine are local injection site reactions, such as pain, redness, or swelling. Some patients may experience mild systemic manifestations, including fatigue, fever, headache, nausea, diarrhea, arthralgias, and myalgias. According to the Centers for Disease Control and Prevention, the approximate wholesale acquisition cost of the vaccine is $320 for 1 injection.

CASE Resolution

This patient is healthy and has no contraindication to the new RSV vaccine. According to the FDA, the optimal time for administration of the vaccine is 32 to 36 weeks of gestation. The patient should anticipate very few side effects following the vaccination, and the vaccine has approximately 80% efficacy in preventing severe lower respiratory tract infection in her neonate. ●

CASE Pregnant woman asks about the RSV vaccine

A 28-year-old primigravid woman at 30 weeks’ gestation inquires about the new vaccine to protect her newborn baby against respiratory syncytial virus infection (RSV). Her neighbor’s daughter recently was hospitalized for the treatment of RSV, and she is understandably concerned about her own newborn. The patient is healthy, and she has never had any serious respiratory infection. She is taking no medications other than prenatal vitamins.

What advice should you give her? 

If you decide to administer this vaccine, what is the appropriate timing of administration?

Are there any maternal or fetal safety concerns related to use of this vaccine in pregnancy?
 

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family. It is an enveloped, single-stranded RNA virus that is 150-300 nm in size. The virus codes for 10 virus-specific proteins. The 2 most important are the G protein, which enables the virus to attach to host cells, and the F protein, which facilitates the entry of the virus into the host cell by fusing the host and viral membranes. Two distinct subtypes exist: A and B. There is genetic variation within each subtype and between subtypes. These subtle genetic variations create the potential for reinfections, and hence, research has focused on development of a vaccine that covers both subtypes.¹

RSV is the most common cause of acute lower respiratory tract infection in infants younger than 6 months of age. In these children, RSV is one of the most prominent causes of death, with mortality particularly marked in low- and middle-resource countries as well as in children who were born premature and/or who are immunocompromised. RSV has its greatest impact during winter epidemics in temperate climates and during the rainy seasons in tropical climates. The virus rarely is encountered in the summer.¹ Among young children, RSV primarily is transmitted via close contact with contaminated fingers or fomites and by self-inoculation of the conjunctiva or anterior nares. The incubation period of the infection is 4 to 6 days, and viral shedding may persist for 2 weeks or longer. Most patients gradually recover within 1 to 2 weeks.¹ Adults who contract RSV usually have symptoms suggestive of a common cold; however, in older adults or those who have comorbidities, serious and potentially life-threatening lower respiratory tract infections may develop.

Recently, there have been 2 main approaches to the prevention and treatment of RSV in infants. One has been the development of monoclonal antibodies such as motavizumab, palivizumab, and nirsevimab. The other has been the development of a vaccine that could be administered to pregnant women and which could provide protection for the neonate in the early months of life.^2,3

In late August 2023, the US Food and Drug Administration (FDA) announced the approval of a new bivalent RSV prefusion F vaccine (ABRYSVO, Pfizer) intended for administration to pregnant women.⁴ Of note, previous efforts to develop whole-virus vaccines either have been ineffective or have potentiated the disease in infants who became infected; development of an effective vaccine had eluded scientists and clinicians for nearly 50 years.² Thus, the new vaccine that targets the F protein of the virus represents a major and welcomed breakthrough.

This article reviews the 3 most recent investigations that preceded the ultimate approval of this vaccine and discusses specific logistical issues related to vaccine administration.

Continue to: First step toward vaccine approval...

First step toward vaccine approval

Madhi and colleagues⁵ were among the first to conduct a large well-designed study to evaluate the effectiveness of maternal vaccination in preventing neonatal infection in the first few months of life. The authors enrolled more than 4,500 healthy pregnant women at 28 to 36 weeks of gestation and assigned them to receive either a single intramuscular dose of an RSV fusion (F) protein vaccine or placebo in a ratio of 2:1. The primary end point was a “medically significant lower respiratory tract infection” within the first 90 days of life. The percentage of infants who met the primary end point was low in both groups: 1.5% in the vaccine group and 2.4% in the placebo group (efficacy 39.4%). The efficacy of the vaccine in preventing lower respiratory tract infection with severe hypoxemia was 48.3% and 44.4% in preventing hospitalization. Although there were differences between the 2 groups, they did not meet the prespecified success criterion for efficacy. Vaccine recipients had more local injection site reactions (40.7% vs 9.9%); however, there was no difference in the frequency of other adverse effects.

Intermediate step: Continued assessment of vaccine safety and immunogenicity

The next important step in the development of the RSV vaccine was a study by Simoes et al,⁶ who conducted a phase 2b trial to determine the safety and immunogenicity of the RSVpreF vaccine. The authors randomly assigned pregnant women at 24 to 36 weeks of gestation to receive either 120 or 240 µg of RSVpreF vaccine or placebo. The key endpoints were the following: maternal and infant safety; the maternal-to-infant transplacental transfer ratio; and the presence of RSV A, B, and combined A/B neutralizing antibody in maternal serum and umbilical cord blood at delivery. The authors conducted a planned interim analysis that included 327 mothers who received the vaccine. The incidence of adverse effects was similar in mothers and infants in the vaccine compared with the placebo group. None of the adverse effects were judged to be serious. The transplacental neutralizing antibody transfer ratios ranged from 1.4 to 2.1 across a range of gestational ages. The vaccine elicited meaningful neutralizing titers of antibody in maternal serum even up to 7 weeks after immunization. The levels of neutralizing antibodies in umbilical cord blood did not vary substantially with respect to gestational age. A post hoc analysis showed that the transferred antibodies prevented medically-attended RSV-associated lower respiratory tract illnesses in the infants.

Final step: Convincing proof of efficacy

The most recent of the 3 studies, and the one that had the greatest impact in convincing the FDA to approve the vaccine, was the report by Kampmann and colleagues.⁷ The authors conducted a phase 3 prospective, randomized, double-blind trial in 18 different countries over 4 RSV seasons: 2 in the northern hemisphere and 2 in the southern hemisphere. They enrolled healthy pregnant women with singleton gestations at 24 to 36 weeks of gestation and assigned them in a 1:1 ratio to a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. They excluded patients with any recognized risk factor for an adverse pregnancy outcome, including preterm labor. The 2 primary efficacy endpoints were a medically-attended severe RSV–lower respiratory tract infection and any medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth.

The efficacy of the vaccine in preventing severe lower respiratory tract illness within 90 days of delivery was 81.8% (99.5% confidence interval [CI], 40.6–96.3). The efficacy within 180 days of delivery was 69.4% (97.58% CI, 44.3–84.1). These differences reached the study’s pre-established statistical criteria for success. The overall rate of lower respiratory tract infections was not significantly different. The frequencies of adverse effects in mothers and infants were similar in the vaccine and placebo groups. In particular, the frequency of preterm delivery in the vaccine group was 0.8%, compared with 0.6% in the placebo group (P = NS).

In previous reports to the FDA,⁴ the frequency rate of preterm delivery in RSV vaccine recipients was slightly increased in vaccine recipients compared with patients who received placebo. The difference among the groups was too small to infer a causal relationship; however, as a condition of vaccine approval, the FDA has required Pfizer to conduct a postmarketing study to be certain that administration of the vaccine does not increase the risk for preterm delivery.

Practical details

The new vaccine is a bivalent recombinant vaccine that elicits a robust antibody response against the F (fusion) protein of the virus. In addition to the F antigen, the vaccine contains the following buffer ingredients: tromethamine, sucrose, mannitol, polysorbate, and sodium chloride.⁸ There are no preservatives in the vaccine.

The vaccine should be administered in a single, 0.5 mL, intramuscular injection at 32 to 36 weeks of gestation. Patients who are allergic to any of the components of the vaccine should not be vaccinated. Patients with a mild upper respiratory tract infection may receive the vaccine. Administration should be delayed in patients who are moderately to severely ill. The vaccine may be administered at the same time as other vaccines, such as influenza or Tdap.

The most common side effects of the vaccine are local injection site reactions, such as pain, redness, or swelling. Some patients may experience mild systemic manifestations, including fatigue, fever, headache, nausea, diarrhea, arthralgias, and myalgias. According to the Centers for Disease Control and Prevention, the approximate wholesale acquisition cost of the vaccine is $320 for 1 injection.

CASE Resolution

This patient is healthy and has no contraindication to the new RSV vaccine. According to the FDA, the optimal time for administration of the vaccine is 32 to 36 weeks of gestation. The patient should anticipate very few side effects following the vaccination, and the vaccine has approximately 80% efficacy in preventing severe lower respiratory tract infection in her neonate. ●

Routine screenings for signs of cavities and gum disease by primary care clinicians may not catch patients most at risk of these conditions, according to a statement by the U.S. Preventive Services Task Force (USPSTF) that was published in JAMA.

Suggesting ways to improve oral health also may fail to engage the patients who most need the message, the group said in its statement.

The task force is not suggesting that primary care providers stop all oral health screening of adults or that they never discuss ways to improve oral health. But the current evidence of the most effective oral health screenings or enhancement strategies in primary care settings received an “I” rating, for “Inconclusive.” The highest ranking a screening can receive is an “A” or “B,” which indicate that there is strong evidence for conducting a screening, while a “C” would indicate that clinicians could rarely provide a screening, and a “D” would indicate not to, given the current evidence.

Primary care clinicians should immediately refer any patients with apparent caries or gum disease to a dentist, the USPSTF noted. But what clinicians should do for patients who have no obvious oral health problems is up for debate.

“The ‘I’ is a note about where the evidence is at this point and then a call for more research to see if we can’t get some more clarity for next time,” said John Ruiz, PhD, professor of clinical psychology at the University of Arizona, Tucson, who is a member of the task force.

More than 90% of U.S. adults may have caries, including 26% with untreated caries that can cause serious infections or tooth loss. In addition, 42% of adults have some type of gum disease. More than two-thirds of Americans aged 65 or older have gum disease, and it is the leading cause of tooth loss in this population. People earning low incomes and those who do not have health insurance or who belong to a marginalized racial or ethnic group are at greater risk of the harms of caries and gum disease.

“Oral health care is important to overall health,” and any new research on oral health screening and enhancement efforts should be demographically representative of adults affected by these conditions, Dr. Ruiz said.

In an accompanying editorial, oral health researchers from the National Institutes of Health and the University of California, San Francisco, echoed the call for representative research and encouraged closer collaboration between primary care providers and dentists to promote oral health.

“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,” the authors wrote. “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.”
 

Lack of data

The USPSTF defined oral health screenings for patients older than 18 who have no obvious signs of caries or gum disease as looking at a patient’s mouth during physical exams. Additionally, clinicians might use prediction models to identify patients at greater risk of facing these problems.

Strategies to improve oral health include providing encouragement to patients to reduce intake of refined sugar, to floss and brush effectively to reduce bacteria, and to use fluoride gels, fluoride varnishes, or other kinds of sealants to make caries harder to form.

A literature review found that there has been limited analysis of primary care clinicians performing these tasks. Perhaps unsurprisingly, more such studies about dentists existed, leaving an open field for dedicated studies about what primary care clinicians should do to optimize oral health with patients.

“Clinicians, in the absence of clear guidelines, should continue to use their best judgment,” Dr. Ruiz said.

One dentist interviewed said screening could be as simple as doctors asking patients how often they brush their teeth and giving patients a toothbrush as part of the office visit.

“It all comes down to, ‘Is the person brushing their teeth?’ ” said Jennifer Hartshorn, DDS, who specializes in community and preventive dentistry at the University of Iowa, Iowa City.

“By all means look in their mouth, ask how much they are brushing, and urge them to find a dental home if at all possible,” Dr. Hartshorn said, especially for patients who smoke or have conditions such as dry mouth, which can increase the risk of oral disease.

Dr. Ruiz and Dr. Hartshorn report no relevant financial relationships.

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

Routine screenings for signs of cavities and gum disease by primary care clinicians may not catch patients most at risk of these conditions, according to a statement by the U.S. Preventive Services Task Force (USPSTF) that was published in JAMA.

Suggesting ways to improve oral health also may fail to engage the patients who most need the message, the group said in its statement.

The task force is not suggesting that primary care providers stop all oral health screening of adults or that they never discuss ways to improve oral health. But the current evidence of the most effective oral health screenings or enhancement strategies in primary care settings received an “I” rating, for “Inconclusive.” The highest ranking a screening can receive is an “A” or “B,” which indicate that there is strong evidence for conducting a screening, while a “C” would indicate that clinicians could rarely provide a screening, and a “D” would indicate not to, given the current evidence.

Primary care clinicians should immediately refer any patients with apparent caries or gum disease to a dentist, the USPSTF noted. But what clinicians should do for patients who have no obvious oral health problems is up for debate.

“The ‘I’ is a note about where the evidence is at this point and then a call for more research to see if we can’t get some more clarity for next time,” said John Ruiz, PhD, professor of clinical psychology at the University of Arizona, Tucson, who is a member of the task force.

More than 90% of U.S. adults may have caries, including 26% with untreated caries that can cause serious infections or tooth loss. In addition, 42% of adults have some type of gum disease. More than two-thirds of Americans aged 65 or older have gum disease, and it is the leading cause of tooth loss in this population. People earning low incomes and those who do not have health insurance or who belong to a marginalized racial or ethnic group are at greater risk of the harms of caries and gum disease.

“Oral health care is important to overall health,” and any new research on oral health screening and enhancement efforts should be demographically representative of adults affected by these conditions, Dr. Ruiz said.

In an accompanying editorial, oral health researchers from the National Institutes of Health and the University of California, San Francisco, echoed the call for representative research and encouraged closer collaboration between primary care providers and dentists to promote oral health.

“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,” the authors wrote. “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.”
 

Lack of data

The USPSTF defined oral health screenings for patients older than 18 who have no obvious signs of caries or gum disease as looking at a patient’s mouth during physical exams. Additionally, clinicians might use prediction models to identify patients at greater risk of facing these problems.

Strategies to improve oral health include providing encouragement to patients to reduce intake of refined sugar, to floss and brush effectively to reduce bacteria, and to use fluoride gels, fluoride varnishes, or other kinds of sealants to make caries harder to form.

A literature review found that there has been limited analysis of primary care clinicians performing these tasks. Perhaps unsurprisingly, more such studies about dentists existed, leaving an open field for dedicated studies about what primary care clinicians should do to optimize oral health with patients.

“Clinicians, in the absence of clear guidelines, should continue to use their best judgment,” Dr. Ruiz said.

One dentist interviewed said screening could be as simple as doctors asking patients how often they brush their teeth and giving patients a toothbrush as part of the office visit.

“It all comes down to, ‘Is the person brushing their teeth?’ ” said Jennifer Hartshorn, DDS, who specializes in community and preventive dentistry at the University of Iowa, Iowa City.

“By all means look in their mouth, ask how much they are brushing, and urge them to find a dental home if at all possible,” Dr. Hartshorn said, especially for patients who smoke or have conditions such as dry mouth, which can increase the risk of oral disease.

Dr. Ruiz and Dr. Hartshorn report no relevant financial relationships.

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

Routine screenings for signs of cavities and gum disease by primary care clinicians may not catch patients most at risk of these conditions, according to a statement by the U.S. Preventive Services Task Force (USPSTF) that was published in JAMA.

Suggesting ways to improve oral health also may fail to engage the patients who most need the message, the group said in its statement.

The task force is not suggesting that primary care providers stop all oral health screening of adults or that they never discuss ways to improve oral health. But the current evidence of the most effective oral health screenings or enhancement strategies in primary care settings received an “I” rating, for “Inconclusive.” The highest ranking a screening can receive is an “A” or “B,” which indicate that there is strong evidence for conducting a screening, while a “C” would indicate that clinicians could rarely provide a screening, and a “D” would indicate not to, given the current evidence.

Primary care clinicians should immediately refer any patients with apparent caries or gum disease to a dentist, the USPSTF noted. But what clinicians should do for patients who have no obvious oral health problems is up for debate.

“The ‘I’ is a note about where the evidence is at this point and then a call for more research to see if we can’t get some more clarity for next time,” said John Ruiz, PhD, professor of clinical psychology at the University of Arizona, Tucson, who is a member of the task force.

More than 90% of U.S. adults may have caries, including 26% with untreated caries that can cause serious infections or tooth loss. In addition, 42% of adults have some type of gum disease. More than two-thirds of Americans aged 65 or older have gum disease, and it is the leading cause of tooth loss in this population. People earning low incomes and those who do not have health insurance or who belong to a marginalized racial or ethnic group are at greater risk of the harms of caries and gum disease.

“Oral health care is important to overall health,” and any new research on oral health screening and enhancement efforts should be demographically representative of adults affected by these conditions, Dr. Ruiz said.

In an accompanying editorial, oral health researchers from the National Institutes of Health and the University of California, San Francisco, echoed the call for representative research and encouraged closer collaboration between primary care providers and dentists to promote oral health.

“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,” the authors wrote. “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.”
 

Lack of data

The USPSTF defined oral health screenings for patients older than 18 who have no obvious signs of caries or gum disease as looking at a patient’s mouth during physical exams. Additionally, clinicians might use prediction models to identify patients at greater risk of facing these problems.

Strategies to improve oral health include providing encouragement to patients to reduce intake of refined sugar, to floss and brush effectively to reduce bacteria, and to use fluoride gels, fluoride varnishes, or other kinds of sealants to make caries harder to form.

A literature review found that there has been limited analysis of primary care clinicians performing these tasks. Perhaps unsurprisingly, more such studies about dentists existed, leaving an open field for dedicated studies about what primary care clinicians should do to optimize oral health with patients.

“Clinicians, in the absence of clear guidelines, should continue to use their best judgment,” Dr. Ruiz said.

One dentist interviewed said screening could be as simple as doctors asking patients how often they brush their teeth and giving patients a toothbrush as part of the office visit.

“It all comes down to, ‘Is the person brushing their teeth?’ ” said Jennifer Hartshorn, DDS, who specializes in community and preventive dentistry at the University of Iowa, Iowa City.

“By all means look in their mouth, ask how much they are brushing, and urge them to find a dental home if at all possible,” Dr. Hartshorn said, especially for patients who smoke or have conditions such as dry mouth, which can increase the risk of oral disease.

Dr. Ruiz and Dr. Hartshorn report no relevant financial relationships.

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

Endoscopy centers may be able to improve their adenoma detection rate (ADR) by employing report cards and ensuring that each procedure is attended by an additional observer, according to results of a recent meta-analysis.

Although multimodal interventions like extra training with periodic feedback showed some signs of improving ADR, withdrawal time monitoring was not significantly associated with a better detection rate, reported Anshul Arora, MD, of Western University, London, Ont., and colleagues.

“Given the increased risk of postcolonoscopy colorectal cancer associated with low ADR, improving [this performance metric] has become a major focus for quality improvement,” the investigators wrote in Clinical Gastroenterology and Hepatology.

They noted that “numerous strategies” have been evaluated for this purpose, which may be sorted into three groups: endoscopy unit–level interventions (i.e., system changes), procedure-targeted interventions (i.e., technique changes), and technology-based interventions.

“Of these categories, endoscopy unit–level interventions are perhaps the easiest to implement widely because they generally require fewer changes in the technical aspect of how a colonoscopy is performed,” the investigators wrote. “Thus, the objective of this study was to conduct a systematic review and meta-analysis to identify endoscopy unit–level interventions aimed at improving ADRs and their effectiveness.”

To this end, Dr. Arora and colleagues analyzed data from 34 randomized controlled trials and observational studies involving 1,501 endoscopists and 371,041 procedures. They evaluated the relationship between ADR and implementation of four interventions: a performance report card, a multimodal intervention (e.g., training sessions with periodic feedback), presence of an additional observer, and withdrawal time monitoring.

Provision of report cards was associated with the greatest improvement in ADR, at 28% (odds ratio, 1.28; 95% confidence interval, 1.13-1.45; P less than .001), followed by presence of an additional observer, which bumped ADR by 25% (OR, 1.25; 95% CI, 1.09-1.43; P = .002). The impact of multimodal interventions was “borderline significant,” the investigators wrote, with an 18% improvement in ADR (OR, 1.18; 95% CI, 1.00-1.40; P = .05). In contrast, withdrawal time monitoring showed no significant benefit (OR, 1.35; 95% CI, 0.93-1.96; P = .11).

In their discussion, Dr. Arora and colleagues offered guidance on the use of report cards, which were associated with the greatest improvement in ADR.

“We found that benchmarking individual endoscopists against their peers was important for improving ADR performance because this was the common thread among all report card–based interventions,” they wrote. “In terms of the method of delivery for feedback, only one study used public reporting of colonoscopy quality indicators, whereas the rest delivered report cards privately to physicians. This suggests that confidential feedback did not impede self-improvement, which is desirable to avoid stigmatization of low ADR performers.”

The findings also suggest that additional observers can boost ADR without specialized training.

“[The benefit of an additional observer] may be explained by the presence of a second set of eyes to identify polyps or, more pragmatically, by the Hawthorne effect, whereby endoscopists may be more careful because they know someone else is watching the screen,” the investigators wrote. “Regardless, extra training for the observer does not seem to be necessary because the three RCTs [evaluating this intervention] all used endoscopy nurses who did not receive any additional polyp detection training. Thus, endoscopy unit nurses should be encouraged to speak up should they see a polyp the endoscopist missed.”

The investigators disclosed no conflicts of interest.

Endoscopy centers may be able to improve their adenoma detection rate (ADR) by employing report cards and ensuring that each procedure is attended by an additional observer, according to results of a recent meta-analysis.

Although multimodal interventions like extra training with periodic feedback showed some signs of improving ADR, withdrawal time monitoring was not significantly associated with a better detection rate, reported Anshul Arora, MD, of Western University, London, Ont., and colleagues.

“Given the increased risk of postcolonoscopy colorectal cancer associated with low ADR, improving [this performance metric] has become a major focus for quality improvement,” the investigators wrote in Clinical Gastroenterology and Hepatology.

They noted that “numerous strategies” have been evaluated for this purpose, which may be sorted into three groups: endoscopy unit–level interventions (i.e., system changes), procedure-targeted interventions (i.e., technique changes), and technology-based interventions.

“Of these categories, endoscopy unit–level interventions are perhaps the easiest to implement widely because they generally require fewer changes in the technical aspect of how a colonoscopy is performed,” the investigators wrote. “Thus, the objective of this study was to conduct a systematic review and meta-analysis to identify endoscopy unit–level interventions aimed at improving ADRs and their effectiveness.”

To this end, Dr. Arora and colleagues analyzed data from 34 randomized controlled trials and observational studies involving 1,501 endoscopists and 371,041 procedures. They evaluated the relationship between ADR and implementation of four interventions: a performance report card, a multimodal intervention (e.g., training sessions with periodic feedback), presence of an additional observer, and withdrawal time monitoring.

Provision of report cards was associated with the greatest improvement in ADR, at 28% (odds ratio, 1.28; 95% confidence interval, 1.13-1.45; P less than .001), followed by presence of an additional observer, which bumped ADR by 25% (OR, 1.25; 95% CI, 1.09-1.43; P = .002). The impact of multimodal interventions was “borderline significant,” the investigators wrote, with an 18% improvement in ADR (OR, 1.18; 95% CI, 1.00-1.40; P = .05). In contrast, withdrawal time monitoring showed no significant benefit (OR, 1.35; 95% CI, 0.93-1.96; P = .11).

In their discussion, Dr. Arora and colleagues offered guidance on the use of report cards, which were associated with the greatest improvement in ADR.

“We found that benchmarking individual endoscopists against their peers was important for improving ADR performance because this was the common thread among all report card–based interventions,” they wrote. “In terms of the method of delivery for feedback, only one study used public reporting of colonoscopy quality indicators, whereas the rest delivered report cards privately to physicians. This suggests that confidential feedback did not impede self-improvement, which is desirable to avoid stigmatization of low ADR performers.”

The findings also suggest that additional observers can boost ADR without specialized training.

“[The benefit of an additional observer] may be explained by the presence of a second set of eyes to identify polyps or, more pragmatically, by the Hawthorne effect, whereby endoscopists may be more careful because they know someone else is watching the screen,” the investigators wrote. “Regardless, extra training for the observer does not seem to be necessary because the three RCTs [evaluating this intervention] all used endoscopy nurses who did not receive any additional polyp detection training. Thus, endoscopy unit nurses should be encouraged to speak up should they see a polyp the endoscopist missed.”

The investigators disclosed no conflicts of interest.

Endoscopy centers may be able to improve their adenoma detection rate (ADR) by employing report cards and ensuring that each procedure is attended by an additional observer, according to results of a recent meta-analysis.

Although multimodal interventions like extra training with periodic feedback showed some signs of improving ADR, withdrawal time monitoring was not significantly associated with a better detection rate, reported Anshul Arora, MD, of Western University, London, Ont., and colleagues.

“Given the increased risk of postcolonoscopy colorectal cancer associated with low ADR, improving [this performance metric] has become a major focus for quality improvement,” the investigators wrote in Clinical Gastroenterology and Hepatology.

They noted that “numerous strategies” have been evaluated for this purpose, which may be sorted into three groups: endoscopy unit–level interventions (i.e., system changes), procedure-targeted interventions (i.e., technique changes), and technology-based interventions.

“Of these categories, endoscopy unit–level interventions are perhaps the easiest to implement widely because they generally require fewer changes in the technical aspect of how a colonoscopy is performed,” the investigators wrote. “Thus, the objective of this study was to conduct a systematic review and meta-analysis to identify endoscopy unit–level interventions aimed at improving ADRs and their effectiveness.”

To this end, Dr. Arora and colleagues analyzed data from 34 randomized controlled trials and observational studies involving 1,501 endoscopists and 371,041 procedures. They evaluated the relationship between ADR and implementation of four interventions: a performance report card, a multimodal intervention (e.g., training sessions with periodic feedback), presence of an additional observer, and withdrawal time monitoring.

Provision of report cards was associated with the greatest improvement in ADR, at 28% (odds ratio, 1.28; 95% confidence interval, 1.13-1.45; P less than .001), followed by presence of an additional observer, which bumped ADR by 25% (OR, 1.25; 95% CI, 1.09-1.43; P = .002). The impact of multimodal interventions was “borderline significant,” the investigators wrote, with an 18% improvement in ADR (OR, 1.18; 95% CI, 1.00-1.40; P = .05). In contrast, withdrawal time monitoring showed no significant benefit (OR, 1.35; 95% CI, 0.93-1.96; P = .11).

In their discussion, Dr. Arora and colleagues offered guidance on the use of report cards, which were associated with the greatest improvement in ADR.

“We found that benchmarking individual endoscopists against their peers was important for improving ADR performance because this was the common thread among all report card–based interventions,” they wrote. “In terms of the method of delivery for feedback, only one study used public reporting of colonoscopy quality indicators, whereas the rest delivered report cards privately to physicians. This suggests that confidential feedback did not impede self-improvement, which is desirable to avoid stigmatization of low ADR performers.”

The findings also suggest that additional observers can boost ADR without specialized training.

“[The benefit of an additional observer] may be explained by the presence of a second set of eyes to identify polyps or, more pragmatically, by the Hawthorne effect, whereby endoscopists may be more careful because they know someone else is watching the screen,” the investigators wrote. “Regardless, extra training for the observer does not seem to be necessary because the three RCTs [evaluating this intervention] all used endoscopy nurses who did not receive any additional polyp detection training. Thus, endoscopy unit nurses should be encouraged to speak up should they see a polyp the endoscopist missed.”

The investigators disclosed no conflicts of interest.

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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

SAN FRANCISCO – Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than 1 month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University, Seoul, Korea, told attendees at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Dr. Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.
 

Three months to 1 month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after less than 1 month of DAPT (n = 1,426) or to ticagrelor-based DAPT for 12 months (n = 1,424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19-80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets less than 100,000/mcL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the less than 1 month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE versus the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

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

TOPLINE:

There are no sex differences in the effectiveness and safety of pulsed field ablation (PFA), a novel modality that uses short, high-energy electrical pulses to treat atrial fibrillation (AFib), results of a large registry study show.

METHODOLOGY:

• The study included all 1,568 patients (mean age 64.5 years and 35.3% women) in the MANIFEST-PF registry, which includes 24 European centers that began using PFA for treating AFib after regulatory approval in 2021.
• Researchers categorized patients by sex and evaluated them for clinical outcomes of PFA, including freedom from AFib and adverse events.
• All patients underwent pulmonary vein isolation (Farawave, Boston Scientific) and were followed up at 3, 6, and 12 months.
• The primary effectiveness outcome was freedom from atrial arrhythmia outside the 90-day blanking period lasting 30 seconds or longer.
• The primary safety outcome included the composite of acute (less than 7 days post-procedure) and chronic (more than 7 days post-procedure) major adverse events, including atrioesophageal fistula, symptomatic pulmonary vein stenosis, cardiac tamponade/perforation requiring intervention or surgery, stroke or systemic thromboembolism, persistent phrenic nerve injury, vascular access complications requiring surgery, coronary artery spasm, and death.

TAKEAWAY:

• There was no significant difference in 12-month recurrence of atrial arrhythmia between male and female patients (79.0% vs 76.3%; P = .28), with greater overall effectiveness in the paroxysmal AFib cohort (men, 82.5% vs women, 80.2%; P = .30) than in the persistent AF/long-standing persistent AFib cohort (men, 73.3% vs women, 67.3%; P = .40).
• Repeated ablation rates were similar between sexes (men, 8.3% vs women, 10.0%; P = .32).
• Among patients who underwent repeat ablation, pulmonary vein isolation durability was higher in female than in male patients (per vein, 82.6% vs 68.1%; P = .15 and per patient, 63.0% vs 37.8%; P = .005).
• Major adverse events occurred in 2.5% of women and 1.5% of men (P = .19), with such events mostly consisting of cardiac tamponade (women, 1.4% vs men, 1.0%; P = .46) and stroke (0.4% vs 0.4%, P > .99), and with no atrioesophageal fistulas or symptomatic pulmonary valve stenosis in either group.

IN PRACTICE:

“These results are important, as women are underrepresented in prior ablation studies and the results have been mixed with regards to both safety and effectiveness using conventional ablation strategies such as radiofrequency or cryoablation,” lead author Mohit Turagam, MD, associate professor of medicine (cardiology), Icahn School of Medicine at Mount Sinai, New York, NY, said in a press release.

In an accompanying commentary, Peter M. Kistler, MBBS, PhD, Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia, and a colleague said that the study authors should be congratulated “for presenting much-needed data on sex-specific outcomes in catheter ablation,” which “reassuringly” suggest that success and safety for AFib ablation are comparable between the sexes, although the study does have “important limitations.”

SOURCE:

The study was conducted by Turagam and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Researchers can’t rule out the possibility that treatment selection and unmeasured confounders between sexes affected the validity of the study findings. The median number of follow-up 24-hour Holter monitors used for AFib monitoring was only two, which may have resulted in inaccurate estimates of AFib recurrence rates and treatment effectiveness.

DISCLOSURES:

The study was supported by Boston Scientific Corporation, the PFA device manufacturer. Turagam has no relevant conflicts of interest; see paper for disclosures of other study authors. The commentary authors have no relevant conflicts of interest.

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

TOPLINE:

There are no sex differences in the effectiveness and safety of pulsed field ablation (PFA), a novel modality that uses short, high-energy electrical pulses to treat atrial fibrillation (AFib), results of a large registry study show.

METHODOLOGY:

• The study included all 1,568 patients (mean age 64.5 years and 35.3% women) in the MANIFEST-PF registry, which includes 24 European centers that began using PFA for treating AFib after regulatory approval in 2021.
• Researchers categorized patients by sex and evaluated them for clinical outcomes of PFA, including freedom from AFib and adverse events.
• All patients underwent pulmonary vein isolation (Farawave, Boston Scientific) and were followed up at 3, 6, and 12 months.
• The primary effectiveness outcome was freedom from atrial arrhythmia outside the 90-day blanking period lasting 30 seconds or longer.
• The primary safety outcome included the composite of acute (less than 7 days post-procedure) and chronic (more than 7 days post-procedure) major adverse events, including atrioesophageal fistula, symptomatic pulmonary vein stenosis, cardiac tamponade/perforation requiring intervention or surgery, stroke or systemic thromboembolism, persistent phrenic nerve injury, vascular access complications requiring surgery, coronary artery spasm, and death.

TAKEAWAY:

• There was no significant difference in 12-month recurrence of atrial arrhythmia between male and female patients (79.0% vs 76.3%; P = .28), with greater overall effectiveness in the paroxysmal AFib cohort (men, 82.5% vs women, 80.2%; P = .30) than in the persistent AF/long-standing persistent AFib cohort (men, 73.3% vs women, 67.3%; P = .40).
• Repeated ablation rates were similar between sexes (men, 8.3% vs women, 10.0%; P = .32).
• Among patients who underwent repeat ablation, pulmonary vein isolation durability was higher in female than in male patients (per vein, 82.6% vs 68.1%; P = .15 and per patient, 63.0% vs 37.8%; P = .005).
• Major adverse events occurred in 2.5% of women and 1.5% of men (P = .19), with such events mostly consisting of cardiac tamponade (women, 1.4% vs men, 1.0%; P = .46) and stroke (0.4% vs 0.4%, P > .99), and with no atrioesophageal fistulas or symptomatic pulmonary valve stenosis in either group.

IN PRACTICE:

“These results are important, as women are underrepresented in prior ablation studies and the results have been mixed with regards to both safety and effectiveness using conventional ablation strategies such as radiofrequency or cryoablation,” lead author Mohit Turagam, MD, associate professor of medicine (cardiology), Icahn School of Medicine at Mount Sinai, New York, NY, said in a press release.

In an accompanying commentary, Peter M. Kistler, MBBS, PhD, Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia, and a colleague said that the study authors should be congratulated “for presenting much-needed data on sex-specific outcomes in catheter ablation,” which “reassuringly” suggest that success and safety for AFib ablation are comparable between the sexes, although the study does have “important limitations.”

SOURCE:

The study was conducted by Turagam and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Researchers can’t rule out the possibility that treatment selection and unmeasured confounders between sexes affected the validity of the study findings. The median number of follow-up 24-hour Holter monitors used for AFib monitoring was only two, which may have resulted in inaccurate estimates of AFib recurrence rates and treatment effectiveness.

DISCLOSURES:

The study was supported by Boston Scientific Corporation, the PFA device manufacturer. Turagam has no relevant conflicts of interest; see paper for disclosures of other study authors. The commentary authors have no relevant conflicts of interest.

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

TOPLINE:

There are no sex differences in the effectiveness and safety of pulsed field ablation (PFA), a novel modality that uses short, high-energy electrical pulses to treat atrial fibrillation (AFib), results of a large registry study show.

METHODOLOGY:

• The study included all 1,568 patients (mean age 64.5 years and 35.3% women) in the MANIFEST-PF registry, which includes 24 European centers that began using PFA for treating AFib after regulatory approval in 2021.
• Researchers categorized patients by sex and evaluated them for clinical outcomes of PFA, including freedom from AFib and adverse events.
• All patients underwent pulmonary vein isolation (Farawave, Boston Scientific) and were followed up at 3, 6, and 12 months.
• The primary effectiveness outcome was freedom from atrial arrhythmia outside the 90-day blanking period lasting 30 seconds or longer.
• The primary safety outcome included the composite of acute (less than 7 days post-procedure) and chronic (more than 7 days post-procedure) major adverse events, including atrioesophageal fistula, symptomatic pulmonary vein stenosis, cardiac tamponade/perforation requiring intervention or surgery, stroke or systemic thromboembolism, persistent phrenic nerve injury, vascular access complications requiring surgery, coronary artery spasm, and death.

TAKEAWAY:

• There was no significant difference in 12-month recurrence of atrial arrhythmia between male and female patients (79.0% vs 76.3%; P = .28), with greater overall effectiveness in the paroxysmal AFib cohort (men, 82.5% vs women, 80.2%; P = .30) than in the persistent AF/long-standing persistent AFib cohort (men, 73.3% vs women, 67.3%; P = .40).
• Repeated ablation rates were similar between sexes (men, 8.3% vs women, 10.0%; P = .32).
• Among patients who underwent repeat ablation, pulmonary vein isolation durability was higher in female than in male patients (per vein, 82.6% vs 68.1%; P = .15 and per patient, 63.0% vs 37.8%; P = .005).
• Major adverse events occurred in 2.5% of women and 1.5% of men (P = .19), with such events mostly consisting of cardiac tamponade (women, 1.4% vs men, 1.0%; P = .46) and stroke (0.4% vs 0.4%, P > .99), and with no atrioesophageal fistulas or symptomatic pulmonary valve stenosis in either group.

IN PRACTICE:

“These results are important, as women are underrepresented in prior ablation studies and the results have been mixed with regards to both safety and effectiveness using conventional ablation strategies such as radiofrequency or cryoablation,” lead author Mohit Turagam, MD, associate professor of medicine (cardiology), Icahn School of Medicine at Mount Sinai, New York, NY, said in a press release.

In an accompanying commentary, Peter M. Kistler, MBBS, PhD, Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia, and a colleague said that the study authors should be congratulated “for presenting much-needed data on sex-specific outcomes in catheter ablation,” which “reassuringly” suggest that success and safety for AFib ablation are comparable between the sexes, although the study does have “important limitations.”

SOURCE:

The study was conducted by Turagam and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Researchers can’t rule out the possibility that treatment selection and unmeasured confounders between sexes affected the validity of the study findings. The median number of follow-up 24-hour Holter monitors used for AFib monitoring was only two, which may have resulted in inaccurate estimates of AFib recurrence rates and treatment effectiveness.

DISCLOSURES:

The study was supported by Boston Scientific Corporation, the PFA device manufacturer. Turagam has no relevant conflicts of interest; see paper for disclosures of other study authors. The commentary authors have no relevant conflicts of interest.

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

The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.

It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”

“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”

The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.

The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.

For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.

However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned. “These medications change [the defended fat mass] to something that is more normal, rather than ‘fixing’ it.”

People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
 

Intermittent therapy: A practical strategy?

The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.

Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”

“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”

Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.

A version of this article appeared on Medscape.com.

The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.

It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”

“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”

The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.

The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.

For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.

However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned. “These medications change [the defended fat mass] to something that is more normal, rather than ‘fixing’ it.”

People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
 

Intermittent therapy: A practical strategy?

The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.

Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”

“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”

Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.

A version of this article appeared on Medscape.com.

The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.

It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”

“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”

The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.

The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.

For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.

However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned. “These medications change [the defended fat mass] to something that is more normal, rather than ‘fixing’ it.”

People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
 

Intermittent therapy: A practical strategy?

The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.

Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”

“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”

Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.

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]