Heidi Splete

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

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

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

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

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

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

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Young adults aged 15-34 years derive no significant health benefits from alcohol consumption, but moderate drinking may benefit the over-40 crowd, according to a new analysis.

The health risks and benefits of moderate alcohol consumption are complex and remain a hot topic of debate. The data suggest that small amounts of alcohol may reduce the risk of certain health outcomes over time, but increase the risk of others, wrote Dana Bryazka, MS, a researcher at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, and colleagues, in a paper published in the Lancet.

“The amount of alcohol that minimizes health loss is likely to depend on the distribution of underlying causes of disease burden in a given population. Since this distribution varies widely by geography, age, sex, and time, the level of alcohol consumption associated with the lowest risk to health would depend on the age structure and disease composition of that population,” the researchers wrote.

“We estimate that 1.78 million people worldwide died due to alcohol use in 2020,” Ms. Bryazka said in an interview. “It is important that alcohol consumption guidelines and policies are updated to minimize this harm, particularly in the populations at greatest risk,” she said.  

“Existing alcohol consumption guidelines frequently vary by sex, with higher consumption thresholds set for males compared to females. Interestingly, with the currently available data we do not see evidence that risk of alcohol use varies by sex,” she noted.
 

Methods and results

In the study, the researchers conducted a systematic analysis of burden-weighted dose-response relative risk curves across 22 health outcomes. They used disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for the years 1990-2020 for 21 regions, including 204 countries and territories. The data were analyzed by 5-year age group, sex, and year for individuals aged 15-95 years and older. The researchers estimated the theoretical minimum risk exposure level (TMREL) and nondrinker equivalent (NDE), meaning the amount of alcohol at which the health risk equals that of a nondrinker.

One standard drink was defined as 10 g of pure alcohol, equivalent to a small glass of red wine (100 mL or 3.4 fluid ounces) at 13% alcohol by volume, a can or bottle of beer (375 mL or 12 fluid ounces) at 3.5% alcohol by volume, or a shot of whiskey or other spirits (30 mL or 1.0 fluid ounces) at 40% alcohol by volume.

Overall, the TMREL was low regardless of age, sex, time, or geography, and varied from 0 to 1.87 standard drinks per day. However, it was lowest for males aged 15-39 years (0.136 drinks per day) and only slightly higher for females aged 15-39 (0.273), representing 1-2 tenths of a standard drink.

For adults aged 40 and older without any underlying health conditions, drinking a small amount of alcohol may provide some benefits, such as reducing the risk of ischemic heart disease, stroke, and diabetes, the researchers noted. In general, for individuals aged 40-64 years, TMRELs ranged from about half a standard drink per day (0.527 drinks for males and 0.562 standard drinks per day for females) to almost two standard drinks (1.69 standard drinks per day for males and 1.82 for females). For those older than 65 years, the TMRELs represented just over 3 standard drinks per day (3.19 for males and 3.51 for females). For individuals aged 40 years and older, the distribution of disease burden varied by region, but was J-shaped across all regions, the researchers noted.

The researchers also found that those individuals consuming harmful amounts of alcohol were most likely to be aged 15-39 (59.1%) and male (76.9%).

The study findings were limited by several factors including the observational design and lack of data on drinking patterns, such as binge drinking, the researchers noted. Other limitations include the lack of data reflecting patterns of alcohol consumption during the COVID-19 pandemic, and exclusion of outcomes often associated with alcohol use, such as depression, anxiety, and dementia, that might reduce estimates of TMREL and NDE.

However, the results add to the ongoing discussion of the relationship between moderate alcohol consumption and health, the researchers said.

“The findings of this study support the development of tailored guidelines and recommendations on alcohol consumption by age and across regions and highlight that existing low consumption thresholds are too high for younger populations in all regions,” they concluded.
 

Consider individual factors when counseling patients

The takeaway message for primary care is that alcohol consumed in moderation can reduce the risk of ischemic heart disease, stroke, and diabetes, Ms. Bryazka noted. “However, it also increases the risk of many cancers, intentional and unintentional injuries, and infectious diseases like tuberculosis,” she said. “Of these health outcomes, young people are most likely to experience injuries, and as a result, we find that there are significant health risks associated with consuming alcohol for young people. Among older individuals, the relative proportions of these outcomes vary by geography, and so do the risks associated with consuming alcohol,” she explained.

“Importantly, our analysis was conducted at the population level; when evaluating risk at the individual level, it is also important to consider other factors such as the presence of comorbidities and interactions between alcohol and medications,” she emphasized.
 

Health and alcohol interaction is complicated

“These findings seemingly contradict a previous [Global Burden of Diseases, Injuries, and Risk Factors Study] estimate published in The Lancet, which emphasized that any alcohol use, regardless of amount, leads to health loss across populations,” wrote Robyn Burton, PhD, and Nick Sheron, MD, both of King’s College, London, in an accompanying comment.

However, the novel methods of weighting relative risk curves according to levels of underlying disease drive the difference in results, along with disaggregated estimates by age, sex, and region, they said.

“Across most geographical regions in this latest analysis, injuries accounted for most alcohol-related harm in younger age groups. This led to a minimum risk level of zero, or very close to zero, among individuals aged 15-39 years across all geographical regions,” which is lower than the level for older adults because of the shift in alcohol-related disease burden towards cardiovascular disease and cancers, they said. “This highlights the need to consider existing rates of disease in a population when trying to determine the total harm posed by alcohol,” the commentators wrote.

In an additional commentary, Tony Rao, MD, a visiting clinical research fellow in psychiatry at King’s College, London, noted that “the elephant in the room with this study is the interpretation of risk based on outcomes for cardiovascular disease – particularly in older people. We know that any purported health benefits from alcohol on the heart and circulation are balanced out by the increased risk from other conditions such as cancer, liver disease, and mental disorders such as depression and dementia,” Dr. Rao said. “If we are to simply draw the conclusion that older people should continue or start drinking small amounts because it protects against diseases affecting heart and circulation – which still remains controversial – other lifestyle changes or the use of drugs targeted at individual cardiovascular disorders seem like a less harmful way of improving health and wellbeing.”

Data can guide clinical practice

No previous study has examined the effect of the theoretical minimum risk of alcohol consumption by geography, age, sex, and time in the context of background disease rates, said Noel Deep, MD, in an interview.

“This study enabled the researchers to quantify the proportion of the population that consumed alcohol in amounts that exceeded the thresholds by location, age, sex, and year, and this can serve as a guide in our efforts to target the control of alcohol intake by individuals,” said Dr. Deep, a general internist in private practice in Antigo, Wisc. He also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The first take-home message for clinicians is that even low levels of alcohol consumption can have deleterious effects on the health of patients, and patients should be advised accordingly based on the prevalence of diseases in that community and geographic area, Dr. Deep said. “Secondly, clinicians should also consider the risk of alcohol consumption on all forms of health impacts in a given population rather than just focusing on alcohol-related health conditions,” he added.

“This study provides us with the data to tailor our efforts in educating the clinicians and the public about the relationship between alcohol consumption and disease outcomes based on the observed disease rates in each population,” Dr. Deep explained. “The data should provide another reason for physicians to advise their younger patients, especially the younger males, to avoid or minimize alcohol use,” he said. The data also can help clinicians formulate public health messaging and community education to reduce harmful alcohol use, he added.

As for additional research, Dr. Deep said he would like to see data on the difference in the health-related effects of alcohol in binge-drinkers vs. those who regularly consume alcohol on a daily basis. “It would probably also be helpful to figure out what type of alcohol is being studied and the quality of the alcohol,” he said.

The study was supported by the Bill and Melinda Gates Foundation. Ms. Bryazka and colleagues had no financial conflicts to disclose. Dr. Burton disclosed serving as a consultant to the World Health Organization European Office for the Prevention and Control of Noncommunicable Diseases. Dr. Sheron had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Internal Medicine News.

The study was supported by the Bill and Melinda Gates Foundation.

Early onset of disease in patients with major depressive disorder may be linked to a specific inflammatory profile, based on data from 234 individuals.

Major depressive disorder (MDD) remains common, and evidence suggests that it is increasing among younger individuals, but data on early-onset MDD in adults are limited, Ana Paula Anzolin, a graduate student at the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues wrote.

Although previous studies have shown abnormal cytokine production in patients with MDD, the impact of inflammation on MDD and disease onset and progression remains unclear, they said.

In a study published in Psychiatry Research, the authors identified outpatients aged 18-85 years with confirmed MDD and scores of at least 8 on the HAM-D scale who were undergoing treatment at a single center. Early onset was defined as a diagnosis of MDD before age 30 years (99 patients) and late onset was defined as a diagnosis at age 30 years and older (135 patients). The researchers measured levels of interleukin-6, IL-1 beta, IL-10, and tumor necrosis factor alpha (TNF-alpha).

Overall, the level of cytokine profiles in early- versus late-onset disease was significantly higher for IL-1B and TNF-alpha (P < .001 for both). The significant difference between early- and late-onset disease remained regardless of comorbidity with autoimmune diseases, the researchers noted.

IL-6 levels were higher in the early-onset group and IL-10 levels were higher in the late-onset group, but these differences were not significant.

“We believe these findings provide a hint that early-onset MDD may be a particular subtype in which the proinflammatory state plays a greater role than in late-onset MDD,” the researchers wrote.

The results also support findings from previous studies that suggest a divergence between early- and late adult–onset depression, they said. More research on early-onset MDD in adults is needed, as these patients tend to have more severe symptoms, more medical and psychiatric comorbidities, and an increased risk of depressive episodes and suicide attempts.

The study findings were limited by several factors including the lack of a control group, the retrospective assessment of disease onset, and the limited cytokines studied, which do not reflect changes in the entire immune network response, the researchers noted.

However, the study is the first known to examine the association of serum cytokines and early- and late-onset MDD in adults, and the results support the use of IL-1B and TNF-alpha as potential treatment targets in the development of new therapies for MDD, they concluded.

The study was supported by the Fundo de Incentivo à Pesquisa – Hospital de Clínicas de Porto Alegre, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The researchers had no financial conflicts to disclose.
 

Early onset of disease in patients with major depressive disorder may be linked to a specific inflammatory profile, based on data from 234 individuals.

Major depressive disorder (MDD) remains common, and evidence suggests that it is increasing among younger individuals, but data on early-onset MDD in adults are limited, Ana Paula Anzolin, a graduate student at the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues wrote.

Although previous studies have shown abnormal cytokine production in patients with MDD, the impact of inflammation on MDD and disease onset and progression remains unclear, they said.

In a study published in Psychiatry Research, the authors identified outpatients aged 18-85 years with confirmed MDD and scores of at least 8 on the HAM-D scale who were undergoing treatment at a single center. Early onset was defined as a diagnosis of MDD before age 30 years (99 patients) and late onset was defined as a diagnosis at age 30 years and older (135 patients). The researchers measured levels of interleukin-6, IL-1 beta, IL-10, and tumor necrosis factor alpha (TNF-alpha).

Overall, the level of cytokine profiles in early- versus late-onset disease was significantly higher for IL-1B and TNF-alpha (P < .001 for both). The significant difference between early- and late-onset disease remained regardless of comorbidity with autoimmune diseases, the researchers noted.

IL-6 levels were higher in the early-onset group and IL-10 levels were higher in the late-onset group, but these differences were not significant.

“We believe these findings provide a hint that early-onset MDD may be a particular subtype in which the proinflammatory state plays a greater role than in late-onset MDD,” the researchers wrote.

The results also support findings from previous studies that suggest a divergence between early- and late adult–onset depression, they said. More research on early-onset MDD in adults is needed, as these patients tend to have more severe symptoms, more medical and psychiatric comorbidities, and an increased risk of depressive episodes and suicide attempts.

The study findings were limited by several factors including the lack of a control group, the retrospective assessment of disease onset, and the limited cytokines studied, which do not reflect changes in the entire immune network response, the researchers noted.

However, the study is the first known to examine the association of serum cytokines and early- and late-onset MDD in adults, and the results support the use of IL-1B and TNF-alpha as potential treatment targets in the development of new therapies for MDD, they concluded.

The study was supported by the Fundo de Incentivo à Pesquisa – Hospital de Clínicas de Porto Alegre, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The researchers had no financial conflicts to disclose.
 

Early onset of disease in patients with major depressive disorder may be linked to a specific inflammatory profile, based on data from 234 individuals.

Major depressive disorder (MDD) remains common, and evidence suggests that it is increasing among younger individuals, but data on early-onset MDD in adults are limited, Ana Paula Anzolin, a graduate student at the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues wrote.

Although previous studies have shown abnormal cytokine production in patients with MDD, the impact of inflammation on MDD and disease onset and progression remains unclear, they said.

In a study published in Psychiatry Research, the authors identified outpatients aged 18-85 years with confirmed MDD and scores of at least 8 on the HAM-D scale who were undergoing treatment at a single center. Early onset was defined as a diagnosis of MDD before age 30 years (99 patients) and late onset was defined as a diagnosis at age 30 years and older (135 patients). The researchers measured levels of interleukin-6, IL-1 beta, IL-10, and tumor necrosis factor alpha (TNF-alpha).

Overall, the level of cytokine profiles in early- versus late-onset disease was significantly higher for IL-1B and TNF-alpha (P < .001 for both). The significant difference between early- and late-onset disease remained regardless of comorbidity with autoimmune diseases, the researchers noted.

IL-6 levels were higher in the early-onset group and IL-10 levels were higher in the late-onset group, but these differences were not significant.

“We believe these findings provide a hint that early-onset MDD may be a particular subtype in which the proinflammatory state plays a greater role than in late-onset MDD,” the researchers wrote.

The results also support findings from previous studies that suggest a divergence between early- and late adult–onset depression, they said. More research on early-onset MDD in adults is needed, as these patients tend to have more severe symptoms, more medical and psychiatric comorbidities, and an increased risk of depressive episodes and suicide attempts.

The study findings were limited by several factors including the lack of a control group, the retrospective assessment of disease onset, and the limited cytokines studied, which do not reflect changes in the entire immune network response, the researchers noted.

However, the study is the first known to examine the association of serum cytokines and early- and late-onset MDD in adults, and the results support the use of IL-1B and TNF-alpha as potential treatment targets in the development of new therapies for MDD, they concluded.

The study was supported by the Fundo de Incentivo à Pesquisa – Hospital de Clínicas de Porto Alegre, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The researchers had no financial conflicts to disclose.