Ob.Gyn. News

Transgender patients have unique needs regarding obstetric and gynecologic care as well as preventive care, and ob.gyns. can help by providing support, education, and understanding, according to new guidance from the American College of Obstetricians and Gynecologists.

“The American College of Obstetricians and Gynecologists opposes discrimination on the basis of gender identity, urges public and private health insurance plans to cover necessary services for individuals with gender dysphoria, and advocates for inclusive, thoughtful, and affirming care for transgender individuals,” according to the committee opinion, published in the March issue of Obstetrics & Gynecology. The opinion was developed jointly by ACOG’s Committee on Gynecologic Practice and Committee on Health Care for Underserved Women, led by Beth Cronin, MD, of Brown University, Providence, R.I., and Colleen K, Stockdale, MD, of the University of Iowa, Iowa City.

“Lack of awareness, knowledge, and sensitivity, as well as bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients,” the authors wrote.

The committee opinion provides guidance for ob.gyns. on topics including inclusivity, routine screening, fertility and reproductive issues, hormone therapy, medication use, and surgery.

“One of the most incredible things about being an ob.gyn. is that this field is a hybrid of primary care and surgical practice,” said K. Ashley Brandt, DO, in an interview. “Many patients seek out care from ob.gyns. for routine screening such as a Pap test, for initiation of hormone therapy, or for postoperative management,” said Dr. Brandt, an ob.gyn. and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa. “Many of my colleagues are starting to see an increase in transgender and gender-nonconforming individuals and do not know where to access resources or information on basic care needs. I think ACOG issuing this guidance is a great first step in providing an overview for the ob.gyn., who otherwise haven’t had formal training in transgender medicine,” she emphasized.

Dr. Brandt said she was not surprised by any of the recommendations. “These recommendations, while evolving and updating as new data emerge, have been in place by WPATH (the World Professional Association for Transgender Health) and the Endocrine Society for quite some time,” she noted. “However, this updated committee opinion is a summary of recommendations that are relevant to the clinical practice of an ob.gyn.”

“Since the publication of Care for Transgender Adolescents (2017) and Healthcare for Transgender Individuals (2011), there has been an exponential increase in data that have helped to improve and guide best practices for this patient population including better defining risks, needs, therapy, and follow-up,” said Nancy Sokkary, MD, a specialist in pediatric and adolescent gynecology in Macon, Ga., in an interview. “This document also served as an opportunity for ACOG to educate ob.gyns. about health inequities and emphasize need for gender-affirming and inclusive care,” she said.

“These recommendations are consistent with literature that has been published over the last several years,” she added. “It is certainly important for ob.gyns. to have a document unequivocally supporting hysterectomies and bilateral salpingo-oophorectomy as medically necessary for transgender patients that desire these procedures for their transition.”
 

Inclusive environment

Approximately 1.4 million adults and 150,000 youth aged 13-17 years in the United States identify as transgender, but these individuals are often marginalized socially and economically, which can lead to worse health outcomes, according to the committee. “Creating a safe and affirming health care environment for all patients, including transgender individuals, is essential,” the authors said. Steps to create a supportive office setting include educating staff to avoid assumptions about sex and gender, and ask appropriately about choice of pronouns and orientation. Use patient forms that reflect a full range of options and places for patients to write in a response. Also, use electronic medical records to track information on use of names other than legal names. “Ob.gyns. play an important role in caring for gender-nonconforming people,” said Dr. Sokkary. “Ob.gyn. providers may have varying levels of participation in gender-affirming hormone or surgery provision, but they can universally conduct routine health maintenance, contraceptive and fertility counseling, and obstetric care in a respectful and inclusive environment,” she said.

Track transition issues

The opinion notes that many gender-transition medications can be prescribed not only by ob.gyns., but by a range of health care professionals with training and education. When it comes to medication and surgery, neither medication nor surgery is required for legally changing one’s name or gender, but patient desires vary from those seeking only letters of support for such legal changes to those who want to pursue hormone therapy or procedures such as chest surgery, hysterectomy, or phalloplasty.

Transgender patients seeking care from ob.gyns. include transmasculine and transfeminine individuals who are seeking various degrees of masculinizing or feminizing therapies.

Masculinizing therapies may result in development of facial hair, deepening voice, and changes in muscle mass, but patients undergoing masculinizing therapies should be reminded of the potential for continued ovulation, according to the opinion. “The only absolute contraindications to masculinizing hormone therapy are current pregnancy, unstable coronary artery disease, and polycythemia (hematocrit greater than 55%),” the authors wrote.

Feminizing therapies have no absolute contraindications, but “risks include venous thromboembolism (VTE), hypertriglyceridemia, development of gallstones, and elevated liver enzymes,” they noted.
 

Talk about sex and fertility

Clinicians treating transgender patients should discuss fertility and parenting early in the process of any gender transition, ideally before the patient undergoes hormone therapy or surgery, according to the opinion. Fertility preservation options for transgender patients are the same as for cisgender patients who wish to preserve fertility for various reasons, and include “sperm banking, oocyte preservation, embryo preservation, and in some cases, ovarian or testicular tissue cryopreservation,” the authors noted.

However, patients who do not desire pregnancy but may have the potential to become pregnant or impregnate others should be counseled on contraceptive options and reminded that gender-affirming hormone therapy alone does not provide effective contraception, they emphasized. In addition, “all patients should be counseled on barrier use for prevention of sexually transmitted diseases,” they said.
 

Consistent routine screening and preventive care

The committee opinion also states that transgender patients should undergo routine screening for any anatomical structures that are present, such as breast cancer screening for transmasculine individuals with breast tissue, and cervical cancer screening for those with a cervix. Transfeminine individuals should undergo prostate cancer screening in accordance with the recommendations for cisgender men, the authors said.

“As for all patients, transgender individuals should be counseled about the importance of routine preventive health care,” according to the opinion. “All individuals should be routinely screened for intimate partner violence, depression, substance use, cancer, and other health care needs and should be screened for sexually transmitted infections and counseled about appropriate immunizations based on age and risk factors, including HPV vaccination,” the authors said.

“We continue to see patient discrimination and discomfort with the medical system as a barrier to preventive care among gender-nonconforming individuals,” said Dr. Sokkary. “[Ensuring] that your clinic is a safe, inclusive place is a good start. Also, having providers such as ob.gyns. and family medicine physicians provide gender-affirming care in addition to routine screening and testing is helpful,” she said. 

One of the ongoing challenges of counseling transgender patients across a range of age groups, from youth through menopause, is a lack of data on the long-term effects of hormone therapy or surgical intervention, Dr. Brandt noted. “Since there is a paucity of this information, many of the screening recommendations fall in line with that of cisgender patients; however, this is not always the case as screening is determined by hormonal usage, risk factors, and surgical state. It is important for clinicians to be aware of evolutions in screening that will continue to occur as more evidence becomes available,” she emphasized.

In addition, “This document did not include specific guidance for transgender and gender-diverse adolescents, and there are many factors and recommendations that are unique to this population,” Dr. Sokkary said.  
 

Barriers and overcoming them

The main barrier to care with transgender and gender-nonconfirming patients is access to care and finding providers who are competent in gender-affirming health, Dr. Brandt noted. “Another significant barrier involves caring for transgender male patients in a traditionally ‘women’s health’ specialty,” she said. “While the office of an ob.gyn. can be very affirming for transgender women, it has the potential to exacerbate discomfort in transgender male patients,” she noted. “Having gender-affirming posters and pamphlets in the waiting area are ways to make patients feel more at ease. Another of the ways to overcome this barrier is education of the staff and health care providers,” added Dr. Brandt. “Fortunately, this is starting to occur at medical school and residency levels. For ob.gyns. already in practice, articles such as this committee opinion can serve as a resource for providers seeking to understand health care needs of this community,” she said.

“Cost and insurance coverage continue to be barriers, but this has improved immensely: There are now several local and national resources that can help with this depending on the issue,” said Dr. Sokkary. “Additionally, we still lack robust data that define cancer risk among transgender individuals, and until we have more evidence-based recommendations providers should follow screening outlined in this document,” she said.
 

Use the ACOG opinion as a starting point

“This committee opinion is a great introduction and summary for ob.gyns. seeking to understand basic care needs for gender-nonconforming individuals,” said Dr. Brandt. “However, I strongly encourage ob.gyns. who wish to truly incorporate gender-affirming care as part of their routine clinical practice to participate in continuing education, read the WPATH standards of care among many of the resources provided in the committee opinion, and attend conferences that are specific to transgender health and medicine,” she said.

The opinion received no outside funding. The authors were vetted by ACOG and had no relevant financial conflicts to disclose. Dr. Brandt had no financial conflicts to disclose. Dr. Sokkary had no financial conflicts to disclose.

Transgender patients have unique needs regarding obstetric and gynecologic care as well as preventive care, and ob.gyns. can help by providing support, education, and understanding, according to new guidance from the American College of Obstetricians and Gynecologists.

“The American College of Obstetricians and Gynecologists opposes discrimination on the basis of gender identity, urges public and private health insurance plans to cover necessary services for individuals with gender dysphoria, and advocates for inclusive, thoughtful, and affirming care for transgender individuals,” according to the committee opinion, published in the March issue of Obstetrics & Gynecology. The opinion was developed jointly by ACOG’s Committee on Gynecologic Practice and Committee on Health Care for Underserved Women, led by Beth Cronin, MD, of Brown University, Providence, R.I., and Colleen K, Stockdale, MD, of the University of Iowa, Iowa City.

“Lack of awareness, knowledge, and sensitivity, as well as bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients,” the authors wrote.

The committee opinion provides guidance for ob.gyns. on topics including inclusivity, routine screening, fertility and reproductive issues, hormone therapy, medication use, and surgery.

“One of the most incredible things about being an ob.gyn. is that this field is a hybrid of primary care and surgical practice,” said K. Ashley Brandt, DO, in an interview. “Many patients seek out care from ob.gyns. for routine screening such as a Pap test, for initiation of hormone therapy, or for postoperative management,” said Dr. Brandt, an ob.gyn. and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa. “Many of my colleagues are starting to see an increase in transgender and gender-nonconforming individuals and do not know where to access resources or information on basic care needs. I think ACOG issuing this guidance is a great first step in providing an overview for the ob.gyn., who otherwise haven’t had formal training in transgender medicine,” she emphasized.

Dr. Brandt said she was not surprised by any of the recommendations. “These recommendations, while evolving and updating as new data emerge, have been in place by WPATH (the World Professional Association for Transgender Health) and the Endocrine Society for quite some time,” she noted. “However, this updated committee opinion is a summary of recommendations that are relevant to the clinical practice of an ob.gyn.”

“Since the publication of Care for Transgender Adolescents (2017) and Healthcare for Transgender Individuals (2011), there has been an exponential increase in data that have helped to improve and guide best practices for this patient population including better defining risks, needs, therapy, and follow-up,” said Nancy Sokkary, MD, a specialist in pediatric and adolescent gynecology in Macon, Ga., in an interview. “This document also served as an opportunity for ACOG to educate ob.gyns. about health inequities and emphasize need for gender-affirming and inclusive care,” she said.

“These recommendations are consistent with literature that has been published over the last several years,” she added. “It is certainly important for ob.gyns. to have a document unequivocally supporting hysterectomies and bilateral salpingo-oophorectomy as medically necessary for transgender patients that desire these procedures for their transition.”
 

Inclusive environment

Approximately 1.4 million adults and 150,000 youth aged 13-17 years in the United States identify as transgender, but these individuals are often marginalized socially and economically, which can lead to worse health outcomes, according to the committee. “Creating a safe and affirming health care environment for all patients, including transgender individuals, is essential,” the authors said. Steps to create a supportive office setting include educating staff to avoid assumptions about sex and gender, and ask appropriately about choice of pronouns and orientation. Use patient forms that reflect a full range of options and places for patients to write in a response. Also, use electronic medical records to track information on use of names other than legal names. “Ob.gyns. play an important role in caring for gender-nonconforming people,” said Dr. Sokkary. “Ob.gyn. providers may have varying levels of participation in gender-affirming hormone or surgery provision, but they can universally conduct routine health maintenance, contraceptive and fertility counseling, and obstetric care in a respectful and inclusive environment,” she said.

Track transition issues

The opinion notes that many gender-transition medications can be prescribed not only by ob.gyns., but by a range of health care professionals with training and education. When it comes to medication and surgery, neither medication nor surgery is required for legally changing one’s name or gender, but patient desires vary from those seeking only letters of support for such legal changes to those who want to pursue hormone therapy or procedures such as chest surgery, hysterectomy, or phalloplasty.

Transgender patients seeking care from ob.gyns. include transmasculine and transfeminine individuals who are seeking various degrees of masculinizing or feminizing therapies.

Masculinizing therapies may result in development of facial hair, deepening voice, and changes in muscle mass, but patients undergoing masculinizing therapies should be reminded of the potential for continued ovulation, according to the opinion. “The only absolute contraindications to masculinizing hormone therapy are current pregnancy, unstable coronary artery disease, and polycythemia (hematocrit greater than 55%),” the authors wrote.

Feminizing therapies have no absolute contraindications, but “risks include venous thromboembolism (VTE), hypertriglyceridemia, development of gallstones, and elevated liver enzymes,” they noted.
 

Talk about sex and fertility

Clinicians treating transgender patients should discuss fertility and parenting early in the process of any gender transition, ideally before the patient undergoes hormone therapy or surgery, according to the opinion. Fertility preservation options for transgender patients are the same as for cisgender patients who wish to preserve fertility for various reasons, and include “sperm banking, oocyte preservation, embryo preservation, and in some cases, ovarian or testicular tissue cryopreservation,” the authors noted.

However, patients who do not desire pregnancy but may have the potential to become pregnant or impregnate others should be counseled on contraceptive options and reminded that gender-affirming hormone therapy alone does not provide effective contraception, they emphasized. In addition, “all patients should be counseled on barrier use for prevention of sexually transmitted diseases,” they said.
 

Consistent routine screening and preventive care

The committee opinion also states that transgender patients should undergo routine screening for any anatomical structures that are present, such as breast cancer screening for transmasculine individuals with breast tissue, and cervical cancer screening for those with a cervix. Transfeminine individuals should undergo prostate cancer screening in accordance with the recommendations for cisgender men, the authors said.

“As for all patients, transgender individuals should be counseled about the importance of routine preventive health care,” according to the opinion. “All individuals should be routinely screened for intimate partner violence, depression, substance use, cancer, and other health care needs and should be screened for sexually transmitted infections and counseled about appropriate immunizations based on age and risk factors, including HPV vaccination,” the authors said.

“We continue to see patient discrimination and discomfort with the medical system as a barrier to preventive care among gender-nonconforming individuals,” said Dr. Sokkary. “[Ensuring] that your clinic is a safe, inclusive place is a good start. Also, having providers such as ob.gyns. and family medicine physicians provide gender-affirming care in addition to routine screening and testing is helpful,” she said. 

One of the ongoing challenges of counseling transgender patients across a range of age groups, from youth through menopause, is a lack of data on the long-term effects of hormone therapy or surgical intervention, Dr. Brandt noted. “Since there is a paucity of this information, many of the screening recommendations fall in line with that of cisgender patients; however, this is not always the case as screening is determined by hormonal usage, risk factors, and surgical state. It is important for clinicians to be aware of evolutions in screening that will continue to occur as more evidence becomes available,” she emphasized.

In addition, “This document did not include specific guidance for transgender and gender-diverse adolescents, and there are many factors and recommendations that are unique to this population,” Dr. Sokkary said.  
 

Barriers and overcoming them

The main barrier to care with transgender and gender-nonconfirming patients is access to care and finding providers who are competent in gender-affirming health, Dr. Brandt noted. “Another significant barrier involves caring for transgender male patients in a traditionally ‘women’s health’ specialty,” she said. “While the office of an ob.gyn. can be very affirming for transgender women, it has the potential to exacerbate discomfort in transgender male patients,” she noted. “Having gender-affirming posters and pamphlets in the waiting area are ways to make patients feel more at ease. Another of the ways to overcome this barrier is education of the staff and health care providers,” added Dr. Brandt. “Fortunately, this is starting to occur at medical school and residency levels. For ob.gyns. already in practice, articles such as this committee opinion can serve as a resource for providers seeking to understand health care needs of this community,” she said.

“Cost and insurance coverage continue to be barriers, but this has improved immensely: There are now several local and national resources that can help with this depending on the issue,” said Dr. Sokkary. “Additionally, we still lack robust data that define cancer risk among transgender individuals, and until we have more evidence-based recommendations providers should follow screening outlined in this document,” she said.
 

Use the ACOG opinion as a starting point

“This committee opinion is a great introduction and summary for ob.gyns. seeking to understand basic care needs for gender-nonconforming individuals,” said Dr. Brandt. “However, I strongly encourage ob.gyns. who wish to truly incorporate gender-affirming care as part of their routine clinical practice to participate in continuing education, read the WPATH standards of care among many of the resources provided in the committee opinion, and attend conferences that are specific to transgender health and medicine,” she said.

The opinion received no outside funding. The authors were vetted by ACOG and had no relevant financial conflicts to disclose. Dr. Brandt had no financial conflicts to disclose. Dr. Sokkary had no financial conflicts to disclose.

Transgender patients have unique needs regarding obstetric and gynecologic care as well as preventive care, and ob.gyns. can help by providing support, education, and understanding, according to new guidance from the American College of Obstetricians and Gynecologists.

“The American College of Obstetricians and Gynecologists opposes discrimination on the basis of gender identity, urges public and private health insurance plans to cover necessary services for individuals with gender dysphoria, and advocates for inclusive, thoughtful, and affirming care for transgender individuals,” according to the committee opinion, published in the March issue of Obstetrics & Gynecology. The opinion was developed jointly by ACOG’s Committee on Gynecologic Practice and Committee on Health Care for Underserved Women, led by Beth Cronin, MD, of Brown University, Providence, R.I., and Colleen K, Stockdale, MD, of the University of Iowa, Iowa City.

“Lack of awareness, knowledge, and sensitivity, as well as bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients,” the authors wrote.

The committee opinion provides guidance for ob.gyns. on topics including inclusivity, routine screening, fertility and reproductive issues, hormone therapy, medication use, and surgery.

“One of the most incredible things about being an ob.gyn. is that this field is a hybrid of primary care and surgical practice,” said K. Ashley Brandt, DO, in an interview. “Many patients seek out care from ob.gyns. for routine screening such as a Pap test, for initiation of hormone therapy, or for postoperative management,” said Dr. Brandt, an ob.gyn. and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa. “Many of my colleagues are starting to see an increase in transgender and gender-nonconforming individuals and do not know where to access resources or information on basic care needs. I think ACOG issuing this guidance is a great first step in providing an overview for the ob.gyn., who otherwise haven’t had formal training in transgender medicine,” she emphasized.

Dr. Brandt said she was not surprised by any of the recommendations. “These recommendations, while evolving and updating as new data emerge, have been in place by WPATH (the World Professional Association for Transgender Health) and the Endocrine Society for quite some time,” she noted. “However, this updated committee opinion is a summary of recommendations that are relevant to the clinical practice of an ob.gyn.”

“Since the publication of Care for Transgender Adolescents (2017) and Healthcare for Transgender Individuals (2011), there has been an exponential increase in data that have helped to improve and guide best practices for this patient population including better defining risks, needs, therapy, and follow-up,” said Nancy Sokkary, MD, a specialist in pediatric and adolescent gynecology in Macon, Ga., in an interview. “This document also served as an opportunity for ACOG to educate ob.gyns. about health inequities and emphasize need for gender-affirming and inclusive care,” she said.

“These recommendations are consistent with literature that has been published over the last several years,” she added. “It is certainly important for ob.gyns. to have a document unequivocally supporting hysterectomies and bilateral salpingo-oophorectomy as medically necessary for transgender patients that desire these procedures for their transition.”
 

Inclusive environment

Approximately 1.4 million adults and 150,000 youth aged 13-17 years in the United States identify as transgender, but these individuals are often marginalized socially and economically, which can lead to worse health outcomes, according to the committee. “Creating a safe and affirming health care environment for all patients, including transgender individuals, is essential,” the authors said. Steps to create a supportive office setting include educating staff to avoid assumptions about sex and gender, and ask appropriately about choice of pronouns and orientation. Use patient forms that reflect a full range of options and places for patients to write in a response. Also, use electronic medical records to track information on use of names other than legal names. “Ob.gyns. play an important role in caring for gender-nonconforming people,” said Dr. Sokkary. “Ob.gyn. providers may have varying levels of participation in gender-affirming hormone or surgery provision, but they can universally conduct routine health maintenance, contraceptive and fertility counseling, and obstetric care in a respectful and inclusive environment,” she said.

Track transition issues

The opinion notes that many gender-transition medications can be prescribed not only by ob.gyns., but by a range of health care professionals with training and education. When it comes to medication and surgery, neither medication nor surgery is required for legally changing one’s name or gender, but patient desires vary from those seeking only letters of support for such legal changes to those who want to pursue hormone therapy or procedures such as chest surgery, hysterectomy, or phalloplasty.

Transgender patients seeking care from ob.gyns. include transmasculine and transfeminine individuals who are seeking various degrees of masculinizing or feminizing therapies.

Masculinizing therapies may result in development of facial hair, deepening voice, and changes in muscle mass, but patients undergoing masculinizing therapies should be reminded of the potential for continued ovulation, according to the opinion. “The only absolute contraindications to masculinizing hormone therapy are current pregnancy, unstable coronary artery disease, and polycythemia (hematocrit greater than 55%),” the authors wrote.

Feminizing therapies have no absolute contraindications, but “risks include venous thromboembolism (VTE), hypertriglyceridemia, development of gallstones, and elevated liver enzymes,” they noted.
 

Talk about sex and fertility

Clinicians treating transgender patients should discuss fertility and parenting early in the process of any gender transition, ideally before the patient undergoes hormone therapy or surgery, according to the opinion. Fertility preservation options for transgender patients are the same as for cisgender patients who wish to preserve fertility for various reasons, and include “sperm banking, oocyte preservation, embryo preservation, and in some cases, ovarian or testicular tissue cryopreservation,” the authors noted.

However, patients who do not desire pregnancy but may have the potential to become pregnant or impregnate others should be counseled on contraceptive options and reminded that gender-affirming hormone therapy alone does not provide effective contraception, they emphasized. In addition, “all patients should be counseled on barrier use for prevention of sexually transmitted diseases,” they said.
 

Consistent routine screening and preventive care

The committee opinion also states that transgender patients should undergo routine screening for any anatomical structures that are present, such as breast cancer screening for transmasculine individuals with breast tissue, and cervical cancer screening for those with a cervix. Transfeminine individuals should undergo prostate cancer screening in accordance with the recommendations for cisgender men, the authors said.

“As for all patients, transgender individuals should be counseled about the importance of routine preventive health care,” according to the opinion. “All individuals should be routinely screened for intimate partner violence, depression, substance use, cancer, and other health care needs and should be screened for sexually transmitted infections and counseled about appropriate immunizations based on age and risk factors, including HPV vaccination,” the authors said.

“We continue to see patient discrimination and discomfort with the medical system as a barrier to preventive care among gender-nonconforming individuals,” said Dr. Sokkary. “[Ensuring] that your clinic is a safe, inclusive place is a good start. Also, having providers such as ob.gyns. and family medicine physicians provide gender-affirming care in addition to routine screening and testing is helpful,” she said. 

One of the ongoing challenges of counseling transgender patients across a range of age groups, from youth through menopause, is a lack of data on the long-term effects of hormone therapy or surgical intervention, Dr. Brandt noted. “Since there is a paucity of this information, many of the screening recommendations fall in line with that of cisgender patients; however, this is not always the case as screening is determined by hormonal usage, risk factors, and surgical state. It is important for clinicians to be aware of evolutions in screening that will continue to occur as more evidence becomes available,” she emphasized.

In addition, “This document did not include specific guidance for transgender and gender-diverse adolescents, and there are many factors and recommendations that are unique to this population,” Dr. Sokkary said.  
 

Barriers and overcoming them

The main barrier to care with transgender and gender-nonconfirming patients is access to care and finding providers who are competent in gender-affirming health, Dr. Brandt noted. “Another significant barrier involves caring for transgender male patients in a traditionally ‘women’s health’ specialty,” she said. “While the office of an ob.gyn. can be very affirming for transgender women, it has the potential to exacerbate discomfort in transgender male patients,” she noted. “Having gender-affirming posters and pamphlets in the waiting area are ways to make patients feel more at ease. Another of the ways to overcome this barrier is education of the staff and health care providers,” added Dr. Brandt. “Fortunately, this is starting to occur at medical school and residency levels. For ob.gyns. already in practice, articles such as this committee opinion can serve as a resource for providers seeking to understand health care needs of this community,” she said.

“Cost and insurance coverage continue to be barriers, but this has improved immensely: There are now several local and national resources that can help with this depending on the issue,” said Dr. Sokkary. “Additionally, we still lack robust data that define cancer risk among transgender individuals, and until we have more evidence-based recommendations providers should follow screening outlined in this document,” she said.
 

Use the ACOG opinion as a starting point

“This committee opinion is a great introduction and summary for ob.gyns. seeking to understand basic care needs for gender-nonconforming individuals,” said Dr. Brandt. “However, I strongly encourage ob.gyns. who wish to truly incorporate gender-affirming care as part of their routine clinical practice to participate in continuing education, read the WPATH standards of care among many of the resources provided in the committee opinion, and attend conferences that are specific to transgender health and medicine,” she said.

The opinion received no outside funding. The authors were vetted by ACOG and had no relevant financial conflicts to disclose. Dr. Brandt had no financial conflicts to disclose. Dr. Sokkary had no financial conflicts to disclose.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson &amp; Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson &amp; Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson &amp; Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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