Female genital cutting (FGC), also known as female circumcision or female genital mutilation, is defined by the World Health Organization (WHO) as “the partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons.”¹ It is a culturally determined practice that is mainly concentrated in certain parts of Africa, the Middle East, and Asia and now is observed worldwide among migrants from those areas.¹ Approximately 200 million women and girls alive today have undergone FGC in 31 countries, although encouragingly the practice’s prevalence seems to be declining, especially among younger women.²

Too often, FGC goes unrecognized in women who present for medical care, even in cases where a genitourinary exam is performed and documented.^3,4 As a result, patients face delays in diagnosis and management of associated complications and symptoms. Female genital cutting is usually excluded from medical school or residency training curricula,⁵ and physicians often lack familiarity with the necessary clinical or surgical management of patients who have had the procedure.⁶ It is crucial, however, that ObGyns feel comfortable recognizing FGC and clinically caring for pregnant and nonpregnant patients who have undergone the procedure. The obstetric-gynecologic setting should be the clinical space in which FGC is correctly diagnosed and from where patients with complications can be referred for appropriate care.

FGC: Through the lens of inequity

Providing culturally competent and sensitive care to women who have undergone FGC is paramount to reducing health care inequities for these patients. Beyond the medical recommendations we review below, we suggest the following considerations when approaching care for these patients.

Acknowledge our biases. It is paramount for us, as providers, to acknowledge our own biases and how these might affect our relationship with the patient and how our care is received. This starts with our language and terminology: The term female genital mutilation can be judgmental or offensive to our patients, many of whom do not consider themselves to have been mutilated. This is why we prefer to use the term female genital cutting, or whichever word the patient uses, so as not to alienate a patient who might already face many other barriers and microaggressions in seeking health care.

Control our responses. Another way we must check our bias is by controlling our reactions during history taking or examining patients who have undergone FGC. Understandably, providers might be shocked to hear patients recount their childhood experiences of FGC or by examining an infibulated scar, but patients report noticing and experiencing hurt, distress, and shame when providers display judgment, horror, or disgust.⁷ Patients have reported that they are acutely aware that they might be viewed as “backward” and “primitive” in US health care settings.⁸ These kinds of feelings and experiences can further exacerbate patients’ distrust and avoidance of the health care system altogether. Therefore, providers should acknowledge their own biases regarding the issue as well as those of their staff and work to mitigate them.

Avoid stigmatization. While FGC can have long-term effects (discussed below), it is important to remember that many women who have undergone FGC do not experience symptoms that are bothersome or feel that FGC is central to their lives or lived experiences. While we must be thorough in our history taking to explore possible urinary, gynecologic, and sexual symptoms of concern and bother to the patient, we must avoid stigmatizing our patients by assuming that all who have undergone FGC are “sexually disabled,” which may lead a provider to recommend medically unindicated intervention, such as clitoral reconstruction.⁹

Continue to: Classifying FGC types...

Classifying FGC types

The WHO has classified FGC into 4 different types¹:

• type 1, partial or total removal of the clitoris or prepuce
• type 2, partial or total removal of part of the clitoris and labia minora
• type 3 (also known as infibulation), the narrowing of the vaginal orifice by cutting, removing, and/or repositioning the labia, and
• type 4, all other procedures to the female genitalia for nonmedical reasons.

Long-term complications

Female genital cutting, especially types 2 and 3, can lead to long-term obstetric and gynecologic complications that the ObGyn should be able to diagnose and manage (TABLE).

The most common long-term complications of FGC are dysmenorrhea, dyspareunia, recurrent vaginal and urinary tract infections, and sexual dysfunction/dissatisfaction.¹⁰ One recent cross-sectional study that used validated questionnaires on pelvic floor and psychosexual symptoms found that women with FGC had higher distress scores than women who had not undergone FGC, indicating various pelvic floor symptoms responsible for impact on their daily lives.¹¹

Infertility can result from a combination of physical barriers (vaginal stenosis and an infibulated scar) and psychologic barriers secondary to dyspareunia, for example.¹² Labor and delivery also presents a challenge to both patients and providers, especially in cases of infibulation. Studies show that patients who have undergone FGC are at increased risk of adverse obstetric outcomes, including postpartum hemorrhage, episiotomy, cesarean delivery, and extended hospital stay.¹³ Neonatal complications, including infant resuscitation and perinatal death, are more commonly reported in studies outside the United States.¹³

Clinical management recommendations

It is important to be aware of the WHO FCG classifications and be able to recognize evidence of the procedure on examination. The ObGyn should perform a detailed physical exam of the external genitalia as well as a pelvic floor exam of every patient. If the patient does not disclose a history of FGC but it is suspected based on the examination, the clinician should inquire sensitively if the patient is aware of having undergone any genital procedures.

Especially when a history of FGC has been confirmed, clinicians should ask patients sensitively about their urinary and sexual function and satisfaction. Validated tools, such as the Female Sexual Function Index, the Female Sexual Distress Scale, and the Pelvic Floor Disability Index, may be helpful in gathering an objective and detailed assessment of the patient’s symptoms and level of distress.¹⁴ Clinicians also should ask about the patient’s detailed obstetric history, particularly regarding the second stage, delivery, and postpartum complications. The clinician also should specifically inquire about a history of defibulation or additional genital procedures.

Patients with urethral strictures or stenosis may require an exam under anesthesia, cystoscopy, urethral dilation, or urethroplasty.¹² Those with chronic urinary tract or vaginal infections may require chronic oral suppressive therapy or defibulation (described below). Defibulation also may be considered for relief of severe dysmenorrhea and menorrhagia that may be resulting from hematocolpos. The ObGyn also should make certain to evaluate for other common causes of these symptoms that may be unrelated to FGC, such as endometriosis.

Many women who have undergone FGC do not report dyspareunia or sexual dissatisfaction; however, infibulation especially has been associated with higher rates of these sequelae.¹² In addition to defibulation, pelvic floor physical therapy with an experienced therapist may be helpful for patients with pelvic floor dysfunction, vaginismus, and/or dyspareunia.

The defibulation procedure

Defibulation (or deinfibulation) is a surgical reconstructive procedure that opens the infibulated scar of patients who have undergone type 3 FGC (infibulation), thus exposing the urethra and introitus, and in almost half of cases an intact clitoris.¹⁵ Defibulation may be specifically requested by a patient or it may be recommended by the ObGyn either for reducing complications of pregnancy or to address the patient’s gynecologic, sexual, or urogynecologic symptoms by allowing penetrative intercourse, urinary flow, physiologic delivery, and menstruation.¹⁶

Defibulation should be performed under regional or general anesthesia and can be performed during pregnancy (or even in labor). An anterior incision is made on the infibulated scar, creating a new labia major, and the edges are sutured separately. Postoperatively, patients should be instructed to perform sitz baths and to expect a change in their urinary voiding stream.¹² The few studies that have evaluated defibulation have shown high rates of success in addressing preoperative symptoms; the complication rates of defibulation are low and the satisfaction rates are high.¹⁶

The ethical conundrum of reinfibulation

Reinfibulation is defined as the restitching or reapproximation of scar tissue or the labia after delivery or a gynecologic procedure, and it is often performed routinely after every delivery in patients’ countries of origin.¹⁷

Postpartum reinfibulation on patient request raises legal and ethical issues for the ObGyn. In the United Kingdom, reinfibulation is illegal, and some international organizations, including the International Federation of Gynecology and Obstetrics and the WHO, have recommended against the practice. In the United States, reinfibulation of an adult is legal, as it falls under the umbrella of elective female genital cosmetic surgery.^18,19

The procedure could create or exacerbate long-term complications and should generally be discouraged. However, if despite extensive counseling (preferably in the prenatal period) a patient insists on having the procedure, the ObGyn may need to elevate the principle of patient autonomy and either comply or find a practitioner who is comfortable performing it. One retrospective review in Switzerland suggested that specific care and informative counseling prenatally with the inclusion of a patient’s partner in the discussion can improve the acceptability of defibulation without reinfibulation.²⁰

Conclusion

It is important for ObGyns to be familiar with the practice of FGC and to be trained in its recognition on examination and care for the long-term complications that can result from the practice. At the same time, ObGyns should be especially conscious of their biases in order to provide culturally competent care and reduce health care stigmatization and inequities for these patients.

Female genital cutting (FGC), also known as female circumcision or female genital mutilation, is defined by the World Health Organization (WHO) as “the partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons.”¹ It is a culturally determined practice that is mainly concentrated in certain parts of Africa, the Middle East, and Asia and now is observed worldwide among migrants from those areas.¹ Approximately 200 million women and girls alive today have undergone FGC in 31 countries, although encouragingly the practice’s prevalence seems to be declining, especially among younger women.²

Too often, FGC goes unrecognized in women who present for medical care, even in cases where a genitourinary exam is performed and documented.^3,4 As a result, patients face delays in diagnosis and management of associated complications and symptoms. Female genital cutting is usually excluded from medical school or residency training curricula,⁵ and physicians often lack familiarity with the necessary clinical or surgical management of patients who have had the procedure.⁶ It is crucial, however, that ObGyns feel comfortable recognizing FGC and clinically caring for pregnant and nonpregnant patients who have undergone the procedure. The obstetric-gynecologic setting should be the clinical space in which FGC is correctly diagnosed and from where patients with complications can be referred for appropriate care.

FGC: Through the lens of inequity

Providing culturally competent and sensitive care to women who have undergone FGC is paramount to reducing health care inequities for these patients. Beyond the medical recommendations we review below, we suggest the following considerations when approaching care for these patients.

Acknowledge our biases. It is paramount for us, as providers, to acknowledge our own biases and how these might affect our relationship with the patient and how our care is received. This starts with our language and terminology: The term female genital mutilation can be judgmental or offensive to our patients, many of whom do not consider themselves to have been mutilated. This is why we prefer to use the term female genital cutting, or whichever word the patient uses, so as not to alienate a patient who might already face many other barriers and microaggressions in seeking health care.

Control our responses. Another way we must check our bias is by controlling our reactions during history taking or examining patients who have undergone FGC. Understandably, providers might be shocked to hear patients recount their childhood experiences of FGC or by examining an infibulated scar, but patients report noticing and experiencing hurt, distress, and shame when providers display judgment, horror, or disgust.⁷ Patients have reported that they are acutely aware that they might be viewed as “backward” and “primitive” in US health care settings.⁸ These kinds of feelings and experiences can further exacerbate patients’ distrust and avoidance of the health care system altogether. Therefore, providers should acknowledge their own biases regarding the issue as well as those of their staff and work to mitigate them.

Avoid stigmatization. While FGC can have long-term effects (discussed below), it is important to remember that many women who have undergone FGC do not experience symptoms that are bothersome or feel that FGC is central to their lives or lived experiences. While we must be thorough in our history taking to explore possible urinary, gynecologic, and sexual symptoms of concern and bother to the patient, we must avoid stigmatizing our patients by assuming that all who have undergone FGC are “sexually disabled,” which may lead a provider to recommend medically unindicated intervention, such as clitoral reconstruction.⁹

Continue to: Classifying FGC types...

Classifying FGC types

The WHO has classified FGC into 4 different types¹:

• type 1, partial or total removal of the clitoris or prepuce
• type 2, partial or total removal of part of the clitoris and labia minora
• type 3 (also known as infibulation), the narrowing of the vaginal orifice by cutting, removing, and/or repositioning the labia, and
• type 4, all other procedures to the female genitalia for nonmedical reasons.

Long-term complications

Female genital cutting, especially types 2 and 3, can lead to long-term obstetric and gynecologic complications that the ObGyn should be able to diagnose and manage (TABLE).

The most common long-term complications of FGC are dysmenorrhea, dyspareunia, recurrent vaginal and urinary tract infections, and sexual dysfunction/dissatisfaction.¹⁰ One recent cross-sectional study that used validated questionnaires on pelvic floor and psychosexual symptoms found that women with FGC had higher distress scores than women who had not undergone FGC, indicating various pelvic floor symptoms responsible for impact on their daily lives.¹¹

Infertility can result from a combination of physical barriers (vaginal stenosis and an infibulated scar) and psychologic barriers secondary to dyspareunia, for example.¹² Labor and delivery also presents a challenge to both patients and providers, especially in cases of infibulation. Studies show that patients who have undergone FGC are at increased risk of adverse obstetric outcomes, including postpartum hemorrhage, episiotomy, cesarean delivery, and extended hospital stay.¹³ Neonatal complications, including infant resuscitation and perinatal death, are more commonly reported in studies outside the United States.¹³

Clinical management recommendations

It is important to be aware of the WHO FCG classifications and be able to recognize evidence of the procedure on examination. The ObGyn should perform a detailed physical exam of the external genitalia as well as a pelvic floor exam of every patient. If the patient does not disclose a history of FGC but it is suspected based on the examination, the clinician should inquire sensitively if the patient is aware of having undergone any genital procedures.

Especially when a history of FGC has been confirmed, clinicians should ask patients sensitively about their urinary and sexual function and satisfaction. Validated tools, such as the Female Sexual Function Index, the Female Sexual Distress Scale, and the Pelvic Floor Disability Index, may be helpful in gathering an objective and detailed assessment of the patient’s symptoms and level of distress.¹⁴ Clinicians also should ask about the patient’s detailed obstetric history, particularly regarding the second stage, delivery, and postpartum complications. The clinician also should specifically inquire about a history of defibulation or additional genital procedures.

Patients with urethral strictures or stenosis may require an exam under anesthesia, cystoscopy, urethral dilation, or urethroplasty.¹² Those with chronic urinary tract or vaginal infections may require chronic oral suppressive therapy or defibulation (described below). Defibulation also may be considered for relief of severe dysmenorrhea and menorrhagia that may be resulting from hematocolpos. The ObGyn also should make certain to evaluate for other common causes of these symptoms that may be unrelated to FGC, such as endometriosis.

Many women who have undergone FGC do not report dyspareunia or sexual dissatisfaction; however, infibulation especially has been associated with higher rates of these sequelae.¹² In addition to defibulation, pelvic floor physical therapy with an experienced therapist may be helpful for patients with pelvic floor dysfunction, vaginismus, and/or dyspareunia.

The defibulation procedure

Defibulation (or deinfibulation) is a surgical reconstructive procedure that opens the infibulated scar of patients who have undergone type 3 FGC (infibulation), thus exposing the urethra and introitus, and in almost half of cases an intact clitoris.¹⁵ Defibulation may be specifically requested by a patient or it may be recommended by the ObGyn either for reducing complications of pregnancy or to address the patient’s gynecologic, sexual, or urogynecologic symptoms by allowing penetrative intercourse, urinary flow, physiologic delivery, and menstruation.¹⁶

Defibulation should be performed under regional or general anesthesia and can be performed during pregnancy (or even in labor). An anterior incision is made on the infibulated scar, creating a new labia major, and the edges are sutured separately. Postoperatively, patients should be instructed to perform sitz baths and to expect a change in their urinary voiding stream.¹² The few studies that have evaluated defibulation have shown high rates of success in addressing preoperative symptoms; the complication rates of defibulation are low and the satisfaction rates are high.¹⁶

The ethical conundrum of reinfibulation

Reinfibulation is defined as the restitching or reapproximation of scar tissue or the labia after delivery or a gynecologic procedure, and it is often performed routinely after every delivery in patients’ countries of origin.¹⁷

Postpartum reinfibulation on patient request raises legal and ethical issues for the ObGyn. In the United Kingdom, reinfibulation is illegal, and some international organizations, including the International Federation of Gynecology and Obstetrics and the WHO, have recommended against the practice. In the United States, reinfibulation of an adult is legal, as it falls under the umbrella of elective female genital cosmetic surgery.^18,19

The procedure could create or exacerbate long-term complications and should generally be discouraged. However, if despite extensive counseling (preferably in the prenatal period) a patient insists on having the procedure, the ObGyn may need to elevate the principle of patient autonomy and either comply or find a practitioner who is comfortable performing it. One retrospective review in Switzerland suggested that specific care and informative counseling prenatally with the inclusion of a patient’s partner in the discussion can improve the acceptability of defibulation without reinfibulation.²⁰

Conclusion

It is important for ObGyns to be familiar with the practice of FGC and to be trained in its recognition on examination and care for the long-term complications that can result from the practice. At the same time, ObGyns should be especially conscious of their biases in order to provide culturally competent care and reduce health care stigmatization and inequities for these patients.

Female genital cutting (FGC), also known as female circumcision or female genital mutilation, is defined by the World Health Organization (WHO) as “the partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons.”¹ It is a culturally determined practice that is mainly concentrated in certain parts of Africa, the Middle East, and Asia and now is observed worldwide among migrants from those areas.¹ Approximately 200 million women and girls alive today have undergone FGC in 31 countries, although encouragingly the practice’s prevalence seems to be declining, especially among younger women.²

Too often, FGC goes unrecognized in women who present for medical care, even in cases where a genitourinary exam is performed and documented.^3,4 As a result, patients face delays in diagnosis and management of associated complications and symptoms. Female genital cutting is usually excluded from medical school or residency training curricula,⁵ and physicians often lack familiarity with the necessary clinical or surgical management of patients who have had the procedure.⁶ It is crucial, however, that ObGyns feel comfortable recognizing FGC and clinically caring for pregnant and nonpregnant patients who have undergone the procedure. The obstetric-gynecologic setting should be the clinical space in which FGC is correctly diagnosed and from where patients with complications can be referred for appropriate care.

FGC: Through the lens of inequity

Providing culturally competent and sensitive care to women who have undergone FGC is paramount to reducing health care inequities for these patients. Beyond the medical recommendations we review below, we suggest the following considerations when approaching care for these patients.

Acknowledge our biases. It is paramount for us, as providers, to acknowledge our own biases and how these might affect our relationship with the patient and how our care is received. This starts with our language and terminology: The term female genital mutilation can be judgmental or offensive to our patients, many of whom do not consider themselves to have been mutilated. This is why we prefer to use the term female genital cutting, or whichever word the patient uses, so as not to alienate a patient who might already face many other barriers and microaggressions in seeking health care.

Control our responses. Another way we must check our bias is by controlling our reactions during history taking or examining patients who have undergone FGC. Understandably, providers might be shocked to hear patients recount their childhood experiences of FGC or by examining an infibulated scar, but patients report noticing and experiencing hurt, distress, and shame when providers display judgment, horror, or disgust.⁷ Patients have reported that they are acutely aware that they might be viewed as “backward” and “primitive” in US health care settings.⁸ These kinds of feelings and experiences can further exacerbate patients’ distrust and avoidance of the health care system altogether. Therefore, providers should acknowledge their own biases regarding the issue as well as those of their staff and work to mitigate them.

Avoid stigmatization. While FGC can have long-term effects (discussed below), it is important to remember that many women who have undergone FGC do not experience symptoms that are bothersome or feel that FGC is central to their lives or lived experiences. While we must be thorough in our history taking to explore possible urinary, gynecologic, and sexual symptoms of concern and bother to the patient, we must avoid stigmatizing our patients by assuming that all who have undergone FGC are “sexually disabled,” which may lead a provider to recommend medically unindicated intervention, such as clitoral reconstruction.⁹

Continue to: Classifying FGC types...

Classifying FGC types

The WHO has classified FGC into 4 different types¹:

• type 1, partial or total removal of the clitoris or prepuce
• type 2, partial or total removal of part of the clitoris and labia minora
• type 3 (also known as infibulation), the narrowing of the vaginal orifice by cutting, removing, and/or repositioning the labia, and
• type 4, all other procedures to the female genitalia for nonmedical reasons.

Long-term complications

Female genital cutting, especially types 2 and 3, can lead to long-term obstetric and gynecologic complications that the ObGyn should be able to diagnose and manage (TABLE).

The most common long-term complications of FGC are dysmenorrhea, dyspareunia, recurrent vaginal and urinary tract infections, and sexual dysfunction/dissatisfaction.¹⁰ One recent cross-sectional study that used validated questionnaires on pelvic floor and psychosexual symptoms found that women with FGC had higher distress scores than women who had not undergone FGC, indicating various pelvic floor symptoms responsible for impact on their daily lives.¹¹

Infertility can result from a combination of physical barriers (vaginal stenosis and an infibulated scar) and psychologic barriers secondary to dyspareunia, for example.¹² Labor and delivery also presents a challenge to both patients and providers, especially in cases of infibulation. Studies show that patients who have undergone FGC are at increased risk of adverse obstetric outcomes, including postpartum hemorrhage, episiotomy, cesarean delivery, and extended hospital stay.¹³ Neonatal complications, including infant resuscitation and perinatal death, are more commonly reported in studies outside the United States.¹³

Clinical management recommendations

It is important to be aware of the WHO FCG classifications and be able to recognize evidence of the procedure on examination. The ObGyn should perform a detailed physical exam of the external genitalia as well as a pelvic floor exam of every patient. If the patient does not disclose a history of FGC but it is suspected based on the examination, the clinician should inquire sensitively if the patient is aware of having undergone any genital procedures.

Especially when a history of FGC has been confirmed, clinicians should ask patients sensitively about their urinary and sexual function and satisfaction. Validated tools, such as the Female Sexual Function Index, the Female Sexual Distress Scale, and the Pelvic Floor Disability Index, may be helpful in gathering an objective and detailed assessment of the patient’s symptoms and level of distress.¹⁴ Clinicians also should ask about the patient’s detailed obstetric history, particularly regarding the second stage, delivery, and postpartum complications. The clinician also should specifically inquire about a history of defibulation or additional genital procedures.

Patients with urethral strictures or stenosis may require an exam under anesthesia, cystoscopy, urethral dilation, or urethroplasty.¹² Those with chronic urinary tract or vaginal infections may require chronic oral suppressive therapy or defibulation (described below). Defibulation also may be considered for relief of severe dysmenorrhea and menorrhagia that may be resulting from hematocolpos. The ObGyn also should make certain to evaluate for other common causes of these symptoms that may be unrelated to FGC, such as endometriosis.

Many women who have undergone FGC do not report dyspareunia or sexual dissatisfaction; however, infibulation especially has been associated with higher rates of these sequelae.¹² In addition to defibulation, pelvic floor physical therapy with an experienced therapist may be helpful for patients with pelvic floor dysfunction, vaginismus, and/or dyspareunia.

The defibulation procedure

Defibulation (or deinfibulation) is a surgical reconstructive procedure that opens the infibulated scar of patients who have undergone type 3 FGC (infibulation), thus exposing the urethra and introitus, and in almost half of cases an intact clitoris.¹⁵ Defibulation may be specifically requested by a patient or it may be recommended by the ObGyn either for reducing complications of pregnancy or to address the patient’s gynecologic, sexual, or urogynecologic symptoms by allowing penetrative intercourse, urinary flow, physiologic delivery, and menstruation.¹⁶

Defibulation should be performed under regional or general anesthesia and can be performed during pregnancy (or even in labor). An anterior incision is made on the infibulated scar, creating a new labia major, and the edges are sutured separately. Postoperatively, patients should be instructed to perform sitz baths and to expect a change in their urinary voiding stream.¹² The few studies that have evaluated defibulation have shown high rates of success in addressing preoperative symptoms; the complication rates of defibulation are low and the satisfaction rates are high.¹⁶

The ethical conundrum of reinfibulation

Reinfibulation is defined as the restitching or reapproximation of scar tissue or the labia after delivery or a gynecologic procedure, and it is often performed routinely after every delivery in patients’ countries of origin.¹⁷

Postpartum reinfibulation on patient request raises legal and ethical issues for the ObGyn. In the United Kingdom, reinfibulation is illegal, and some international organizations, including the International Federation of Gynecology and Obstetrics and the WHO, have recommended against the practice. In the United States, reinfibulation of an adult is legal, as it falls under the umbrella of elective female genital cosmetic surgery.^18,19

The procedure could create or exacerbate long-term complications and should generally be discouraged. However, if despite extensive counseling (preferably in the prenatal period) a patient insists on having the procedure, the ObGyn may need to elevate the principle of patient autonomy and either comply or find a practitioner who is comfortable performing it. One retrospective review in Switzerland suggested that specific care and informative counseling prenatally with the inclusion of a patient’s partner in the discussion can improve the acceptability of defibulation without reinfibulation.²⁰

Conclusion

It is important for ObGyns to be familiar with the practice of FGC and to be trained in its recognition on examination and care for the long-term complications that can result from the practice. At the same time, ObGyns should be especially conscious of their biases in order to provide culturally competent care and reduce health care stigmatization and inequities for these patients.

COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.

If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.

“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.

The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.

“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
 

Still aiming for herd immunity

Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.

Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”

In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.

As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.

Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
 

Masks and the uncommon cold

Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.

Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.

“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
 

Variants: Some good news?

Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.

Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.

“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
 

Hesitancy from misinformation

Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.

“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.

Even celebrities are getting drawn into the misinformation.

“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”

Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
 

The future is subject to change

“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.

However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.

Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”

“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”

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

COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.

If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.

“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.

The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.

“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
 

Still aiming for herd immunity

Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.

Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”

In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.

As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.

Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
 

Masks and the uncommon cold

Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.

Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.

“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
 

Variants: Some good news?

Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.

Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.

“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
 

Hesitancy from misinformation

Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.

“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.

Even celebrities are getting drawn into the misinformation.

“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”

Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
 

The future is subject to change

“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.

However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.

Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”

“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”

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

COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.

If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.

“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.

The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.

“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
 

Still aiming for herd immunity

Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.

Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”

In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.

As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.

Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
 

Masks and the uncommon cold

Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.

Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.

“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
 

Variants: Some good news?

Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.

Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.

“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
 

Hesitancy from misinformation

Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.

“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.

Even celebrities are getting drawn into the misinformation.

“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”

Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
 

The future is subject to change

“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.

However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.

Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”

“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”

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

Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.

According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.

Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.

Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.

Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.

State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”

Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”

Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.

The White House had not responded to a request from this news organization for comment by press time.

Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
 

Bringing pediatricians on board

Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.

She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.

Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.

The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.

Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.

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

Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.

According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.

Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.

Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.

Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.

State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”

Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”

Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.

The White House had not responded to a request from this news organization for comment by press time.

Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
 

Bringing pediatricians on board

Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.

She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.

Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.

The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.

Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.

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

Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.

According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.

Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.

Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.

Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.

State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”

Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”

Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.

The White House had not responded to a request from this news organization for comment by press time.

Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
 

Bringing pediatricians on board

Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.

She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.

Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.

The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.

Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.

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

Background: The beneficial role of high-intensity statins in secondary prevention of recurrent atherosclerotic stroke is well established. It is uncertain whether the observed benefit was from a reduction in the cholesterol level or to other pleotropic effects of atorvastatin. The ideal target cholesterol level for secondary prevention is unclear. This trial was conducted to help determine an ideal target LDL-C level in the prevention of CV events following ischemic stroke.

There were 2,860 patients enrolled, 1,430 were assigned to each target group. At the end of 3.5 years, the primary endpoint occurred in 8.5% of patients in the lower target group, compared with 10.9% in the higher target group (hazard ratio, 0.78; 95% confidence interval, 0.61-0.98; P = .04). Unfortunately, the trial was stopped early because of a lack of funding.

Bottom line: Using medications including statins to lower the LDL-C to less than 70 mg/dL leads to better cardiovascular outcomes following ischemic stroke.

Citation: Amarenco P et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020 Jan 2;382:9-19.

Dr. Garg is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: The beneficial role of high-intensity statins in secondary prevention of recurrent atherosclerotic stroke is well established. It is uncertain whether the observed benefit was from a reduction in the cholesterol level or to other pleotropic effects of atorvastatin. The ideal target cholesterol level for secondary prevention is unclear. This trial was conducted to help determine an ideal target LDL-C level in the prevention of CV events following ischemic stroke.

There were 2,860 patients enrolled, 1,430 were assigned to each target group. At the end of 3.5 years, the primary endpoint occurred in 8.5% of patients in the lower target group, compared with 10.9% in the higher target group (hazard ratio, 0.78; 95% confidence interval, 0.61-0.98; P = .04). Unfortunately, the trial was stopped early because of a lack of funding.

Bottom line: Using medications including statins to lower the LDL-C to less than 70 mg/dL leads to better cardiovascular outcomes following ischemic stroke.

Citation: Amarenco P et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020 Jan 2;382:9-19.

Dr. Garg is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: The beneficial role of high-intensity statins in secondary prevention of recurrent atherosclerotic stroke is well established. It is uncertain whether the observed benefit was from a reduction in the cholesterol level or to other pleotropic effects of atorvastatin. The ideal target cholesterol level for secondary prevention is unclear. This trial was conducted to help determine an ideal target LDL-C level in the prevention of CV events following ischemic stroke.

There were 2,860 patients enrolled, 1,430 were assigned to each target group. At the end of 3.5 years, the primary endpoint occurred in 8.5% of patients in the lower target group, compared with 10.9% in the higher target group (hazard ratio, 0.78; 95% confidence interval, 0.61-0.98; P = .04). Unfortunately, the trial was stopped early because of a lack of funding.

Bottom line: Using medications including statins to lower the LDL-C to less than 70 mg/dL leads to better cardiovascular outcomes following ischemic stroke.

Citation: Amarenco P et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020 Jan 2;382:9-19.

Dr. Garg is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

Oral evobrutinib, an investigational highly selective Bruton’s tyrosine kinase inhibitor, may have a beneficial effect on reducing nerve damage in multiple sclerosis (MS), based on how it’s been found to lower levels of a key blood biomarker, according to a post hoc analysis of a placebo-controlled clinical trial reported at the American Academy of Neurology’s 2021 annual meeting.

Jens Kuhle, MD, of the department of biomedicine at University Hospital Basel, Switzerland, said the conclusion was based on reductions in blood levels of neurofilament light chain (NfL), a biomarker of neuroaxonal damage, in treated patients. “These data on the effect of evobrutinib on NfL dynamics are the first to be reported for a BTK inhibitor investigated for MS,” Dr. Kuhle said. Evobrutinib targets beta cells and myeloid cells, including macrophages and microglia, to disrupt NfL production.

The analysis consisted of three treatment arms in addition to the placebo arm: 25 and 75 mg daily, and 75 mg twice daily. The post hoc analysis included 166 patients across all arms, with 148 being evaluated at week 24.

Dr. Kuhle said the 75-mg twice-daily group exhibited significantly lower blood NfL levels as early as week 12 with lowered levels maintained to week 24, the last time point the study evaluated – specifically reductions of 18.9% (P = .01) and 16.8% (P = .040) compared with placebo, respectively.

However, the 75-mg once daily dose also showed meaningful reductions when compared with placebo: 15.4% (P = .043) and 14.1% (P = .10) at 12 and 24 weeks, respectively, Dr. Kuhle said. “There were no significant differences seen with the 25-mg once-daily group,” he said.

“These results are promising and indicate evobrutinib at an efficacious dose of 75 mg twice daily has a beneficial effect on reducing neuroaxonal damage in MS,” he said.

In an interview, Dr. Kuhle explained the importance of lower NfL levels. “The hope is that detecting subclinical disease activity in a sensitive and comprehensive way will lead to more effective treatment of the individual MS patient,” he said.

The findings may also inform future studies of evobrutinib in MS, he said. “Neurofilaments and neurons are the key substrate of permanent disability in MS and other neurodegenerative diseases,” Dr. Kuhle said. “It is anticipated that normalization of NfL to levels in same-age healthy controls should be the adequate treatment target for individual patients.”

NfL could be an “easily accessible and modifiable biomarker” for use in clinical trials of relapsing and progressive MS, he said. The researchers plan to use NfL measurements in the extension phase of the trial.

“An important next step is the development of reliable and age-adjusted reference values for NfL measurements in blood to move this biomarker further toward individual application in clinical practice,” he added, noting that his group has already collected more than 10,000 serum samples from more than 5,000 healthy controls to do that.

The analysis adds to the growing body of evidence supporting the use of blood NfL levels to gauge the effectiveness of disease-modifying therapies on neuroaxonal degeneration in MS, said Fredrik Piehl, MD, PhD, a professor at Karolinska University Hospital in Stockholm.

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved a new indication for ALK’s under-the-tongue immunotherapy tablet Ragwitek (Ambrosia artemisiifolia) to treat ragweed pollen–induced hay fever in children aged 5-17 years.

Olivier Le Moal/Getty Images

Ragwitek received FDA approval in 2014 to treat short ragweed pollen–induced hay fever, with or without allergic rhinoconjunctivitis, in adults aged 18-65 years. This new indication expanded that age group to include children.

The approval for Ragwitek comes with a boxed warning regarding a risk for life-threatening allergic reactions associated with the immunotherapy treatment, including anaphylaxis and severe laryngopharyngeal restriction. The package insert specifies that physicians should prescribe autoinjectable epinephrine with the drug.

“Ragwitek tablets provide a new immunotherapy treatment option for children and adolescents with seasonal ragweed allergies which often causes uncomfortable nasal symptoms and red, itchy eyes during the late summer and early fall,” David I. Bernstein, MD, University of Cincinnati, Bernstein Clinical Research, said in a company press release. 

Short ragweed pollen is one of the most common weed allergies. Allergic rhinitis, or hay fever, affects 10%-30% of the population worldwide, according to the American Academy of Allergy Asthma & Immunology. In the United States, approximately 7.7% of adults and 7.2% of children were diagnosed with it annually, according to the Centers for Disease Control and Prevention.

The new indication was based partly on data from a phase 3 clinical trial in children with short ragweed–induced allergic rhinitis, or hay fever, published in the Journal of Allergy and Clinical Immunology. In the study, researchers evaluated the efficacy and safety of the treatment in 1,022 participants aged 5-17 years with a history of ragweed-induced rhinoconjunctivitis and sensitivity to ragweed over a 20- to 28-week treatment period.

Researchers found that Ragwitek improved symptoms in children and adolescents and decreased their use of symptom-relieving medication, compared with placebo.

Among children and adolescents aged 5-17 years, the most common adverse reactions reported were throat irritation/tickle (48.3% in the Ragwitek group vs. 17.7% in the placebo group), itching in the mouth (47.8% vs. 11.2%), itching in the ear (33.9% vs. 6.3%), mouth pain (18.9% vs. 4.5%), swelling of the lips (13.8% vs. 1.2%), nausea (11.5% vs. 3.3%), swelling of the tongue (11.3% vs. 0.8%), throat swelling (10.7% vs. 1.6%), and stomach pain (10.1% vs. 4.5%).

The FDA also recommends that Ragwitek not be prescribed to people with severe, unstable, or uncontrolled asthma, those with a history of severe systemic allergic reactions, and those with a history of eosinophilic esophagitis. The immunotherapy treatment also may not be suitable for people who are unresponsive to epinephrine or inhaled bronchodilators.

In addition, the treatment is not approved for the immediate relief of allergic symptoms in children or adults. The once-daily treatment, which contains an extract from short ragweed pollen, should begin 12 weeks before the start of ragweed pollen season and continue throughout the season, according to the FDA.

Dr. Bernstein said that the under-the-tongue immunotherapy works by targeting the specific allergy trigger and reducing allergy symptoms by “stimulating the immune system.”

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

The Food and Drug Administration has approved a new indication for ALK’s under-the-tongue immunotherapy tablet Ragwitek (Ambrosia artemisiifolia) to treat ragweed pollen–induced hay fever in children aged 5-17 years.

Olivier Le Moal/Getty Images

Ragwitek received FDA approval in 2014 to treat short ragweed pollen–induced hay fever, with or without allergic rhinoconjunctivitis, in adults aged 18-65 years. This new indication expanded that age group to include children.

The approval for Ragwitek comes with a boxed warning regarding a risk for life-threatening allergic reactions associated with the immunotherapy treatment, including anaphylaxis and severe laryngopharyngeal restriction. The package insert specifies that physicians should prescribe autoinjectable epinephrine with the drug.

“Ragwitek tablets provide a new immunotherapy treatment option for children and adolescents with seasonal ragweed allergies which often causes uncomfortable nasal symptoms and red, itchy eyes during the late summer and early fall,” David I. Bernstein, MD, University of Cincinnati, Bernstein Clinical Research, said in a company press release. 

Short ragweed pollen is one of the most common weed allergies. Allergic rhinitis, or hay fever, affects 10%-30% of the population worldwide, according to the American Academy of Allergy Asthma & Immunology. In the United States, approximately 7.7% of adults and 7.2% of children were diagnosed with it annually, according to the Centers for Disease Control and Prevention.

The new indication was based partly on data from a phase 3 clinical trial in children with short ragweed–induced allergic rhinitis, or hay fever, published in the Journal of Allergy and Clinical Immunology. In the study, researchers evaluated the efficacy and safety of the treatment in 1,022 participants aged 5-17 years with a history of ragweed-induced rhinoconjunctivitis and sensitivity to ragweed over a 20- to 28-week treatment period.

Researchers found that Ragwitek improved symptoms in children and adolescents and decreased their use of symptom-relieving medication, compared with placebo.

Among children and adolescents aged 5-17 years, the most common adverse reactions reported were throat irritation/tickle (48.3% in the Ragwitek group vs. 17.7% in the placebo group), itching in the mouth (47.8% vs. 11.2%), itching in the ear (33.9% vs. 6.3%), mouth pain (18.9% vs. 4.5%), swelling of the lips (13.8% vs. 1.2%), nausea (11.5% vs. 3.3%), swelling of the tongue (11.3% vs. 0.8%), throat swelling (10.7% vs. 1.6%), and stomach pain (10.1% vs. 4.5%).

The FDA also recommends that Ragwitek not be prescribed to people with severe, unstable, or uncontrolled asthma, those with a history of severe systemic allergic reactions, and those with a history of eosinophilic esophagitis. The immunotherapy treatment also may not be suitable for people who are unresponsive to epinephrine or inhaled bronchodilators.

In addition, the treatment is not approved for the immediate relief of allergic symptoms in children or adults. The once-daily treatment, which contains an extract from short ragweed pollen, should begin 12 weeks before the start of ragweed pollen season and continue throughout the season, according to the FDA.

Dr. Bernstein said that the under-the-tongue immunotherapy works by targeting the specific allergy trigger and reducing allergy symptoms by “stimulating the immune system.”

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

The Food and Drug Administration has approved a new indication for ALK’s under-the-tongue immunotherapy tablet Ragwitek (Ambrosia artemisiifolia) to treat ragweed pollen–induced hay fever in children aged 5-17 years.

Olivier Le Moal/Getty Images

Ragwitek received FDA approval in 2014 to treat short ragweed pollen–induced hay fever, with or without allergic rhinoconjunctivitis, in adults aged 18-65 years. This new indication expanded that age group to include children.

The approval for Ragwitek comes with a boxed warning regarding a risk for life-threatening allergic reactions associated with the immunotherapy treatment, including anaphylaxis and severe laryngopharyngeal restriction. The package insert specifies that physicians should prescribe autoinjectable epinephrine with the drug.

“Ragwitek tablets provide a new immunotherapy treatment option for children and adolescents with seasonal ragweed allergies which often causes uncomfortable nasal symptoms and red, itchy eyes during the late summer and early fall,” David I. Bernstein, MD, University of Cincinnati, Bernstein Clinical Research, said in a company press release. 

Short ragweed pollen is one of the most common weed allergies. Allergic rhinitis, or hay fever, affects 10%-30% of the population worldwide, according to the American Academy of Allergy Asthma & Immunology. In the United States, approximately 7.7% of adults and 7.2% of children were diagnosed with it annually, according to the Centers for Disease Control and Prevention.

The new indication was based partly on data from a phase 3 clinical trial in children with short ragweed–induced allergic rhinitis, or hay fever, published in the Journal of Allergy and Clinical Immunology. In the study, researchers evaluated the efficacy and safety of the treatment in 1,022 participants aged 5-17 years with a history of ragweed-induced rhinoconjunctivitis and sensitivity to ragweed over a 20- to 28-week treatment period.

Researchers found that Ragwitek improved symptoms in children and adolescents and decreased their use of symptom-relieving medication, compared with placebo.

Among children and adolescents aged 5-17 years, the most common adverse reactions reported were throat irritation/tickle (48.3% in the Ragwitek group vs. 17.7% in the placebo group), itching in the mouth (47.8% vs. 11.2%), itching in the ear (33.9% vs. 6.3%), mouth pain (18.9% vs. 4.5%), swelling of the lips (13.8% vs. 1.2%), nausea (11.5% vs. 3.3%), swelling of the tongue (11.3% vs. 0.8%), throat swelling (10.7% vs. 1.6%), and stomach pain (10.1% vs. 4.5%).

The FDA also recommends that Ragwitek not be prescribed to people with severe, unstable, or uncontrolled asthma, those with a history of severe systemic allergic reactions, and those with a history of eosinophilic esophagitis. The immunotherapy treatment also may not be suitable for people who are unresponsive to epinephrine or inhaled bronchodilators.

In addition, the treatment is not approved for the immediate relief of allergic symptoms in children or adults. The once-daily treatment, which contains an extract from short ragweed pollen, should begin 12 weeks before the start of ragweed pollen season and continue throughout the season, according to the FDA.

Dr. Bernstein said that the under-the-tongue immunotherapy works by targeting the specific allergy trigger and reducing allergy symptoms by “stimulating the immune system.”

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

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]

Mitochondrial DNA (mtDNA) copy number alterations are known to occur in acute myeloid leukemia (AML), however their biological significance has not been well studied. Pediatric AML has a distinct biology, different from adults, and with heterogeneous clinical outcomes, the biological basis of which are not well understood, according to researchers Shilpi Chaudhary, PhD, of the All India Institute of Medical Sciences, New Delhi, and colleagues.

wir0man/GettyImages

Their analysis of 123 pediatric patients with AML found that mtDNA copy number was an independent predictor of aggressive disease, lower event-free survival, and overall survival, according to a report published in Mitochondrion.

In an attempt to find the biological factors involved in the increased mtDNA copy numbers and their effect on the development and aggressiveness of pediatric AML, the researchers studied the regulation and significance of mtDNA copy number in pediatric AML patients using quantitative real time–polymerase chain reaction, as well as in vitro studies. For patients, results were correlated with clinical outcomes.

Mitochondrial biogenesis genes (TFAM, POLG, POLRMT) and two regulator of mitochondrial biogenesis, MYC and PGC1A, were also assessed, according to Dr. Chaudhary and colleagues.
 

Predictive results

MtDNA copy number was significantly higher in patients, compared with controls (P < .001) and was found to be an independent predictor of aggressive disease (P = .006), lower event-free survival (P = .033), and overall survival (P = .007).

TFAM, POLG & POLRMT and ND3 were also found to be significantly up-regulated in patients, compared with controls as was the expression of the mitochondrial biogenesis regulator MYC (P < .001). However, correlation analysis showed that mtDNA copy number was not associated with the expression of these genes.

In contrast, PGC1A expression was not significantly different in patients, compared with controls overall, although there was a subset of patients whose PGC1A expression was extremely high, according to the researchers.

Importantly, however, in the subset of patients with high PGC1A expression (n = 28), mtDNA copy number had a positive correlation with PGC1A expression (P = .013). On the other hand, among patients with low MYC expression (n = 27), there was no correlation of mtDNA copy number with either PGC1A or MYC expression.

These results were corroborated in in vitro studies, where treatment with the inhibitor tigecycline led to a significant decrease in expression of MYC (P < .001), TFAM (P = .037) and ND3 (P = .010) but resulted in no significant change in mtDNA copy number (P = .23) or expression of PGC1A (P = .10).
 

Therapeutic candidate?

In contrast to the case of MYC, in vitro PGC1A inhibition significantly reduced mtDNA copy number in along with expression of TFAM and even expression of POLG and POLRMT at higher concentration.

“This observation is in line with our finding in patient samples as well that PGC1A expression positively correlated with mtDNA copy number, more so in patients with higher PGC1A expression,” the researchers stated.

“This makes it plausible to infer that PGC1A may have a possible role in enhancing mtDNA copy number in AML patients, likely independent of MYC,” they added. “Therefore, a strategy of designing therapeutics using already approved inhibitors targeting PGC1A may be an exciting area of therapeutic intervention.”

The authors reported that they have no competing financial conflicts of interests.

[email protected]

In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.

These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.

“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.

“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”

The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”

Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.

“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
 

Measuring failure to rescue across racial and ethnic groups

According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.

Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.

The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.

Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).

Yet racial and ethnic inequities were apparent.

Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).

“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
 

Striving for progress through systemic change

According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”

“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”

Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.

“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
 

Comparing the U.S. with the rest of the world

In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.

They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.

“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”

Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.

“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”

To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”

The study received no external funding. The investigators reported no conflicts of interest.

In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.

These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.

“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.

“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”

The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”

Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.

“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
 

Measuring failure to rescue across racial and ethnic groups

According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.

Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.

The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.

Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).

Yet racial and ethnic inequities were apparent.

Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).

“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
 

Striving for progress through systemic change

According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”

“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”

Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.

“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
 

Comparing the U.S. with the rest of the world

In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.

They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.

“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”

Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.

“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”

To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”

The study received no external funding. The investigators reported no conflicts of interest.

In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.

These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.

“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.

“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”

The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”

Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.

“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
 

Measuring failure to rescue across racial and ethnic groups

According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.

Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.

The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.

Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).

Yet racial and ethnic inequities were apparent.

Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).

“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
 

Striving for progress through systemic change

According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”

“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”

Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.

“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
 

Comparing the U.S. with the rest of the world

In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.

They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.

“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”

Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.

“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”

To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”

The study received no external funding. The investigators reported no conflicts of interest.