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Scientists use mRNA technology for universal flu vaccine
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
FROM SCIENCE
Researchers probe ‘systematic error’ in gun injury data
These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.
“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”
In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.
For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.
Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.
Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.
ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.
The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.
Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.
Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.
Trends and interventions
Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.
Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.
They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.
Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.
To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.
They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.
“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.
The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.
Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
A version of this article first appeared on Medscape.com.
These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.
“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”
In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.
For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.
Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.
Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.
ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.
The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.
Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.
Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.
Trends and interventions
Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.
Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.
They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.
Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.
To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.
They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.
“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.
The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.
Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
A version of this article first appeared on Medscape.com.
These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.
“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”
In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.
For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.
Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.
Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.
ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.
The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.
Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.
Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.
Trends and interventions
Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.
Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.
They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.
Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.
To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.
They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.
“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.
The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.
Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
COVID booster shot poll: People ‘don’t think they need one’
Now, a new poll shows why so few people are willing to roll up their sleeves again.
The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation.
The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.
Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling.
So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.
Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.
Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.
“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.
Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.
Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.
“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”
A version of this article first appeared on WebMD.com.
Now, a new poll shows why so few people are willing to roll up their sleeves again.
The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation.
The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.
Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling.
So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.
Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.
Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.
“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.
Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.
Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.
“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”
A version of this article first appeared on WebMD.com.
Now, a new poll shows why so few people are willing to roll up their sleeves again.
The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation.
The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.
Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling.
So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.
Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.
Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.
“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.
Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.
Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.
“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”
A version of this article first appeared on WebMD.com.
Hospitals with more diverse and uninsured patients more likely to provide delayed fracture care
Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.
“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.
“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.
The study was published online in JAMA Network Open.
Site performance varied
Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.
The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.
The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.
The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.
Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.
The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).
At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.
There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.
At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.
Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
Addressing inequalities
Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”
Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.
“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”
Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.
“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.
Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.
“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”
Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.
“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”
The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.
“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.
“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.
The study was published online in JAMA Network Open.
Site performance varied
Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.
The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.
The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.
The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.
Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.
The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).
At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.
There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.
At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.
Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
Addressing inequalities
Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”
Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.
“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”
Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.
“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.
Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.
“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”
Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.
“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”
The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.
“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.
“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.
The study was published online in JAMA Network Open.
Site performance varied
Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.
The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.
The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.
The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.
Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.
The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).
At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.
There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.
At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.
Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
Addressing inequalities
Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”
Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.
“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”
Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.
“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.
Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.
“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”
Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.
“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”
The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
FDA will review pediatric indication for roflumilast cream
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.
, according to a press release from the manufacturer.
The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.
The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.
Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.
Multiple myeloma diagnosed more via emergency care during COVID
The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.
Study design
Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.
Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
Key results
Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.
Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).
Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.
Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).
Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID.
Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
Limitations
The study does not provide a clear time frame of delays in diagnosis.
Disclosures
The study authors did not report any conflicts of interest.
A version of this article first appeared on Medscape.com .
The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.
Study design
Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.
Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
Key results
Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.
Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).
Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.
Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).
Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID.
Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
Limitations
The study does not provide a clear time frame of delays in diagnosis.
Disclosures
The study authors did not report any conflicts of interest.
A version of this article first appeared on Medscape.com .
The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
While trying to avoid COVID-19 infection, patients ultimately diagnosed with multiple myeloma may have delayed interactions with healthcare professionals and consequently delayed their cancer diagnosis.
Study design
Researchers collected data on newly diagnosed patients with multiple myeloma from January 2019 until July 2021 across five institutions (three universities and two hospitals) in England. In total, 323 patients with multiple myeloma were identified.
Patients were divided into two groups: those diagnosed between Jan. 1, 2019, until Jan. 31, 2020, or pre-COVID, and those diagnosed from Feb. 1, 2020, to July 31, 2021, or post COVID.
Key results
Among all patients, 80 (24.8%) were diagnosed with smoldering multiple myeloma and 243 (75.2%) were diagnosed with multiple myeloma requiring treatment.
Significantly more patients in the post-COVID group were diagnosed with myeloma through the emergency route (45.5% post COVID vs. 32.7% pre-COVID; P = .03).
Clinical complications leading to emergency admission prior to a myeloma diagnosis also differed between the two cohorts: Acute kidney injury accounted for most emergency admissions in the pre-COVID cohort while skeletal-related events, including spinal cord compression, were the major causes for diagnosis through the emergency route in the post-COVID cohort.
Patients who were diagnosed with symptomatic myeloma pre-COVID were more likely to be treated with a triplet rather than doublet combination compared with those diagnosed in the post-COVID period (triplet pre-COVID 79.1%, post COVID 63.75%; P = .014).
Overall survival at 1 year was not significantly different between the pre-COVID and post-COVID groups: 88.2% pre-COVID, compared with 87.8% post COVID.
Overall, the authors concluded that the COVID pandemic “resulted in a shift in the symptomatology, disease burden, and routes of diagnosis of patients presenting with myeloma” and “this may have significant consequences” over the long term.
Limitations
The study does not provide a clear time frame of delays in diagnosis.
Disclosures
The study authors did not report any conflicts of interest.
A version of this article first appeared on Medscape.com .
Bite-sized bouts of exercise: Why they are valuable and what they are missing
Short bursts of activity are approximately as effective for general health as longer sessions, especially for those who are mainly sedentary, according to several recently published studies.
If your fitness goals are greater, and you want to build muscle strength and endurance, compete in a 5K, or just look better in your swimsuit, you will need to do more. But for basic health, it appears that short bursts can help, the new research papers and experts suggest.
“Whether you accumulate activity in many short bouts versus one extended bout, the general health benefits tend to be similar,” Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, said in an interview.
Current public health recommendations from the Centers for Disease Control and Prevention suggest doing at least 150 minutes of moderate intensity physical activity per week for health benefits, but this activity can be accumulated in any way over the week, she noted. Previous versions of the CDC guidelines on exercise suggested that physical activity bouts should be at least 10 minutes each, but the latest version of the guidelines acknowledges that bursts of less than 10 minutes may be beneficial.
However, “the activity or fitness level at which someone starts and the specific health goals matter,” Dr. Paluch continued. “Short bouts may be particularly beneficial for those least active to get moving more to improve their general wellness.”
The current federal physical activity guidelines are still worth striving for, and patients can work their way to this goal, accumulating 150 or more minutes in a way that works best for them, she added.
“There is a lack of research directly comparing individuals who consistently accumulate their activity in many short bouts versus single bouts over an extended period of time,” Dr. Paluch noted. From a public health perspective, since both short and long bouts have health benefits, the best physical activity is what fits into your life and helps build a lifelong habit.
The benefits of exercise for cardiovascular health are well documented. A review from Circulation published in 2003 summarized the benefits of regular physical activity on measures of cardiovascular health including reduction in body weight, blood pressure, and bad cholesterol, while increasing insulin sensitivity, good cholesterol, and muscular strength and function. In that review, author Jonathan N. Myers, PhD, now of Stanford (Calif.) University, noted that “one need not be a marathon runner or an elite athlete to derive significant benefits from physical activity.” In fact, “the greatest gains in terms of mortality are achieved when an individual goes from being sedentary to becoming moderately active.”
A recent large, population-based study showed the value of short bursts of exercise for those previously sedentary. In this study, published in Nature Medicine, a team in Australia used wearable fitness trackers to measure the health benefits of what researchers have named “vigorous intermittent lifestyle physical activity” or VILPA.
Some examples of VILPA include power walking on the way to work, climbing stairs, or even running around with your kids on the playground.
Specifically, individuals who engaged in the median VILPA frequency of three bursts of vigorous activity lasting 1-2 minutes showed a 38%-40% reduction in all-cause mortality risk and cancer mortality risk, and a 48%-49% reduction in cardiovascular mortality risk.
The researchers repeated their analysis for a group of 62,344 adults from the UK Biobank who reported regular vigorous physical activity (VPA). They found similar effects on mortality, based on 1,552 deaths reported.
These results suggest that VILPA may be a reasonable physical activity target, especially for people not able or willing to exercise more formally or intensely, the researchers noted.
“We have known for a long time that leisure-time exercise often reaches vigorous intensity and has many health benefits, but we understand less about the health potential of daily movement, especially activities done as part of daily living that reach vigorous intensity,” lead author Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle and population health at the University of Sydney’s Charles Perkins Centre, said in an interview.
“As long as the heart rate goes up for a minute or 2 it will likely be vigorous activity,” Dr. Stamatakis said in an interview. “It is also important that clinicians effectively communicate how patients can know that they are reaching vigorous intensity,” he said.
Signs of vigorous intensity include increased heart rate and getting out of breath after about 20-40 seconds from the start of the VILPA burst. After about a minute of VILPA, the person doing it should be too out of breath to speak more than a few words comfortably, he said.
Data support value of any and all exercise
The Nature Medicine study supports other recent research showing the value of short, intense bursts of physical activity. A pair of recent studies also used fitness trackers to measure activity in adults and assess the benefits on outcomes including death and heart disease.
One of these studies, which was published in the European Heart Journal, also used fitness trackers to measure physical activity at moderate and vigorous levels. The researchers found that individuals who performed at least 20% of their physical activity at a moderate to high level, such as by doing brisk walking in lieu of strolling had a significantly lower risk of heart disease than those whose daily activity included less than 20% at a moderate or intense level.
In another study from the European Heart Journal, researchers found that short bursts of vigorous physical activity of 2 minutes or less adding up to 15-20 minutes per week was enough to reduce mortality by as much as 40%.
Plus, a meta-analysis published in the Lancet showed a decrease in all-cause mortality with an increase in the number of daily steps, although the impact of stepping rate on mortality was inconsistent.
“Many studies have investigated the health benefits of physical activity, but not the importance of these difficult-to-capture VILPA bouts that accrue during the course of normal activities of daily living,” Lee Stoner, PhD, an exercise physiologist and director of the Cardiometabolic Lab at the University of North Carolina at Chapel Hill, said in an interview.
Dr. Stoner, who was not involved in the Nature Medicine study, said he was not surprised by the overall finding that doing short bursts of activity impacted mortality and cardiovascular disease, but was slightly surprised by the strength of the evidence.
“The referent group in the Nature Medicine study were those accruing no VILPA”, likely meaning they were very inactive,” Dr. Stoner said and added that he thinks this demonstrates the value of VILPA.
Even without immediately meeting the specific numbers recommended by the CDC, “any physical activity is better than none, especially if vigorous, and VILPA can be built into normal daily routines,” Dr. Stoner added.
What’s missing in short bursts?
Short bursts of activity do have their limits when it comes to overall fitness, said Dr. Stoner.
“Endurance will not be improved as much through short bursts, because such activities are unlikely to be as effective at empowering the mitochondria – the batteries keeping our cells running, including skeletal muscle cells,” he said. “Additionally, the vigorous bouts are unlikely to be as effective at improving muscular strength and endurance. For this, it is recommended that we engage each muscle group in strengthening exercises two times per week.”
However, Dr. Stoner agreed that prescribing short bursts of intense activity as part of daily living may be a great way to get people started with exercise.
“The key is to remove barriers to physical activity pursuit, then focusing on long-term routine rather than short-term gain,” he said. “Individuals are better served if they focus on goals other than weight loss, for which physical activity or exercise may not be the solution. Rather, being physically active can improve vigor, make daily activities simpler, and improve cognitive abilities,” and any physical activity is one of the most effective solutions for regulating blood glucose levels and improving cardiovascular risk factors.
Make it routine – and fun
To benefit from physical activity, cultivating and sustaining a long-term routine is key, said Dr. Stoner, whose research has focused on sedentary behavior and cardiovascular disease. Whatever the activity is, shorter bursts, or longer bouts or both, it is essential that individuals figure out activities that they enjoy if they want to create sustained behavior, and thus health change, Gabriel Zieff, MA, a doctoral candidate in Dr. Stoner’s Cardiometabolic Lab, who conducts studies on exercise, noted in an interview.
“We exercise enthusiasts and researchers are often hyperfocused on whether this duration or that duration is better, whether this intensity or that intensity is better,” but at the end of the day, it is the enjoyment factor that often predicts sustained behavior change, and should be part of discussions with patients to help reduce sedentary behavior and promote activity, Mr. Zieff said.
Short bouts can encourage hesitant exercisers
“To best support health, clinicians should consider taking a few seconds to ask patients about their physical activity levels,” said Dr. Paluch, who was the lead author on the Lancet meta-analysis of daily steps. In that study, Dr. Paluch and colleagues found that taking more steps each day was associated with a progressively lower risk of all-cause mortality. However, that study did not measure step rate.
Clinicians can emphasize that health benefits do not require an hour-long exercise routine and special equipment, and moving more, even in shorts bursts of activity can have meaningful associations with health, particularly for those who are less active, she said.
The recent studies on short bursts of activity agree that “some physical activity is better than none and adults should move more throughout the day in whatever way makes sense to them and fits best into their lives,” said Dr. Paluch. “For example, opting for the stairs instead of the elevator, a brisk walk to the bus stop, a short game of hide and seek with the children or grandchildren – anything that gets your body moving more, even if briefly. Making simple lifestyle changes is often easier in small bites. In time, this can grow into long-term habits, ultimately leading to an overall active lifestyle that supports living healthier for longer.”
The Nature Medicine study was supported by the Australian National Health and Medical Research Council. Several coauthors were supported by the Wellcome Trust, the National Institute for Health Research Oxford Biomedical Research Centre, Novo Nordisk, the British Heart Foundation Centre of Research Excellence, the Alan Turing Institute, the British Heart Foundation, and Health Data Research UK, an initiative funded by UK Research and Innovation. Dr. Paluch and Dr. Stoner had no financial conflicts to disclose.
Short bursts of activity are approximately as effective for general health as longer sessions, especially for those who are mainly sedentary, according to several recently published studies.
If your fitness goals are greater, and you want to build muscle strength and endurance, compete in a 5K, or just look better in your swimsuit, you will need to do more. But for basic health, it appears that short bursts can help, the new research papers and experts suggest.
“Whether you accumulate activity in many short bouts versus one extended bout, the general health benefits tend to be similar,” Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, said in an interview.
Current public health recommendations from the Centers for Disease Control and Prevention suggest doing at least 150 minutes of moderate intensity physical activity per week for health benefits, but this activity can be accumulated in any way over the week, she noted. Previous versions of the CDC guidelines on exercise suggested that physical activity bouts should be at least 10 minutes each, but the latest version of the guidelines acknowledges that bursts of less than 10 minutes may be beneficial.
However, “the activity or fitness level at which someone starts and the specific health goals matter,” Dr. Paluch continued. “Short bouts may be particularly beneficial for those least active to get moving more to improve their general wellness.”
The current federal physical activity guidelines are still worth striving for, and patients can work their way to this goal, accumulating 150 or more minutes in a way that works best for them, she added.
“There is a lack of research directly comparing individuals who consistently accumulate their activity in many short bouts versus single bouts over an extended period of time,” Dr. Paluch noted. From a public health perspective, since both short and long bouts have health benefits, the best physical activity is what fits into your life and helps build a lifelong habit.
The benefits of exercise for cardiovascular health are well documented. A review from Circulation published in 2003 summarized the benefits of regular physical activity on measures of cardiovascular health including reduction in body weight, blood pressure, and bad cholesterol, while increasing insulin sensitivity, good cholesterol, and muscular strength and function. In that review, author Jonathan N. Myers, PhD, now of Stanford (Calif.) University, noted that “one need not be a marathon runner or an elite athlete to derive significant benefits from physical activity.” In fact, “the greatest gains in terms of mortality are achieved when an individual goes from being sedentary to becoming moderately active.”
A recent large, population-based study showed the value of short bursts of exercise for those previously sedentary. In this study, published in Nature Medicine, a team in Australia used wearable fitness trackers to measure the health benefits of what researchers have named “vigorous intermittent lifestyle physical activity” or VILPA.
Some examples of VILPA include power walking on the way to work, climbing stairs, or even running around with your kids on the playground.
Specifically, individuals who engaged in the median VILPA frequency of three bursts of vigorous activity lasting 1-2 minutes showed a 38%-40% reduction in all-cause mortality risk and cancer mortality risk, and a 48%-49% reduction in cardiovascular mortality risk.
The researchers repeated their analysis for a group of 62,344 adults from the UK Biobank who reported regular vigorous physical activity (VPA). They found similar effects on mortality, based on 1,552 deaths reported.
These results suggest that VILPA may be a reasonable physical activity target, especially for people not able or willing to exercise more formally or intensely, the researchers noted.
“We have known for a long time that leisure-time exercise often reaches vigorous intensity and has many health benefits, but we understand less about the health potential of daily movement, especially activities done as part of daily living that reach vigorous intensity,” lead author Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle and population health at the University of Sydney’s Charles Perkins Centre, said in an interview.
“As long as the heart rate goes up for a minute or 2 it will likely be vigorous activity,” Dr. Stamatakis said in an interview. “It is also important that clinicians effectively communicate how patients can know that they are reaching vigorous intensity,” he said.
Signs of vigorous intensity include increased heart rate and getting out of breath after about 20-40 seconds from the start of the VILPA burst. After about a minute of VILPA, the person doing it should be too out of breath to speak more than a few words comfortably, he said.
Data support value of any and all exercise
The Nature Medicine study supports other recent research showing the value of short, intense bursts of physical activity. A pair of recent studies also used fitness trackers to measure activity in adults and assess the benefits on outcomes including death and heart disease.
One of these studies, which was published in the European Heart Journal, also used fitness trackers to measure physical activity at moderate and vigorous levels. The researchers found that individuals who performed at least 20% of their physical activity at a moderate to high level, such as by doing brisk walking in lieu of strolling had a significantly lower risk of heart disease than those whose daily activity included less than 20% at a moderate or intense level.
In another study from the European Heart Journal, researchers found that short bursts of vigorous physical activity of 2 minutes or less adding up to 15-20 minutes per week was enough to reduce mortality by as much as 40%.
Plus, a meta-analysis published in the Lancet showed a decrease in all-cause mortality with an increase in the number of daily steps, although the impact of stepping rate on mortality was inconsistent.
“Many studies have investigated the health benefits of physical activity, but not the importance of these difficult-to-capture VILPA bouts that accrue during the course of normal activities of daily living,” Lee Stoner, PhD, an exercise physiologist and director of the Cardiometabolic Lab at the University of North Carolina at Chapel Hill, said in an interview.
Dr. Stoner, who was not involved in the Nature Medicine study, said he was not surprised by the overall finding that doing short bursts of activity impacted mortality and cardiovascular disease, but was slightly surprised by the strength of the evidence.
“The referent group in the Nature Medicine study were those accruing no VILPA”, likely meaning they were very inactive,” Dr. Stoner said and added that he thinks this demonstrates the value of VILPA.
Even without immediately meeting the specific numbers recommended by the CDC, “any physical activity is better than none, especially if vigorous, and VILPA can be built into normal daily routines,” Dr. Stoner added.
What’s missing in short bursts?
Short bursts of activity do have their limits when it comes to overall fitness, said Dr. Stoner.
“Endurance will not be improved as much through short bursts, because such activities are unlikely to be as effective at empowering the mitochondria – the batteries keeping our cells running, including skeletal muscle cells,” he said. “Additionally, the vigorous bouts are unlikely to be as effective at improving muscular strength and endurance. For this, it is recommended that we engage each muscle group in strengthening exercises two times per week.”
However, Dr. Stoner agreed that prescribing short bursts of intense activity as part of daily living may be a great way to get people started with exercise.
“The key is to remove barriers to physical activity pursuit, then focusing on long-term routine rather than short-term gain,” he said. “Individuals are better served if they focus on goals other than weight loss, for which physical activity or exercise may not be the solution. Rather, being physically active can improve vigor, make daily activities simpler, and improve cognitive abilities,” and any physical activity is one of the most effective solutions for regulating blood glucose levels and improving cardiovascular risk factors.
Make it routine – and fun
To benefit from physical activity, cultivating and sustaining a long-term routine is key, said Dr. Stoner, whose research has focused on sedentary behavior and cardiovascular disease. Whatever the activity is, shorter bursts, or longer bouts or both, it is essential that individuals figure out activities that they enjoy if they want to create sustained behavior, and thus health change, Gabriel Zieff, MA, a doctoral candidate in Dr. Stoner’s Cardiometabolic Lab, who conducts studies on exercise, noted in an interview.
“We exercise enthusiasts and researchers are often hyperfocused on whether this duration or that duration is better, whether this intensity or that intensity is better,” but at the end of the day, it is the enjoyment factor that often predicts sustained behavior change, and should be part of discussions with patients to help reduce sedentary behavior and promote activity, Mr. Zieff said.
Short bouts can encourage hesitant exercisers
“To best support health, clinicians should consider taking a few seconds to ask patients about their physical activity levels,” said Dr. Paluch, who was the lead author on the Lancet meta-analysis of daily steps. In that study, Dr. Paluch and colleagues found that taking more steps each day was associated with a progressively lower risk of all-cause mortality. However, that study did not measure step rate.
Clinicians can emphasize that health benefits do not require an hour-long exercise routine and special equipment, and moving more, even in shorts bursts of activity can have meaningful associations with health, particularly for those who are less active, she said.
The recent studies on short bursts of activity agree that “some physical activity is better than none and adults should move more throughout the day in whatever way makes sense to them and fits best into their lives,” said Dr. Paluch. “For example, opting for the stairs instead of the elevator, a brisk walk to the bus stop, a short game of hide and seek with the children or grandchildren – anything that gets your body moving more, even if briefly. Making simple lifestyle changes is often easier in small bites. In time, this can grow into long-term habits, ultimately leading to an overall active lifestyle that supports living healthier for longer.”
The Nature Medicine study was supported by the Australian National Health and Medical Research Council. Several coauthors were supported by the Wellcome Trust, the National Institute for Health Research Oxford Biomedical Research Centre, Novo Nordisk, the British Heart Foundation Centre of Research Excellence, the Alan Turing Institute, the British Heart Foundation, and Health Data Research UK, an initiative funded by UK Research and Innovation. Dr. Paluch and Dr. Stoner had no financial conflicts to disclose.
Short bursts of activity are approximately as effective for general health as longer sessions, especially for those who are mainly sedentary, according to several recently published studies.
If your fitness goals are greater, and you want to build muscle strength and endurance, compete in a 5K, or just look better in your swimsuit, you will need to do more. But for basic health, it appears that short bursts can help, the new research papers and experts suggest.
“Whether you accumulate activity in many short bouts versus one extended bout, the general health benefits tend to be similar,” Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, said in an interview.
Current public health recommendations from the Centers for Disease Control and Prevention suggest doing at least 150 minutes of moderate intensity physical activity per week for health benefits, but this activity can be accumulated in any way over the week, she noted. Previous versions of the CDC guidelines on exercise suggested that physical activity bouts should be at least 10 minutes each, but the latest version of the guidelines acknowledges that bursts of less than 10 minutes may be beneficial.
However, “the activity or fitness level at which someone starts and the specific health goals matter,” Dr. Paluch continued. “Short bouts may be particularly beneficial for those least active to get moving more to improve their general wellness.”
The current federal physical activity guidelines are still worth striving for, and patients can work their way to this goal, accumulating 150 or more minutes in a way that works best for them, she added.
“There is a lack of research directly comparing individuals who consistently accumulate their activity in many short bouts versus single bouts over an extended period of time,” Dr. Paluch noted. From a public health perspective, since both short and long bouts have health benefits, the best physical activity is what fits into your life and helps build a lifelong habit.
The benefits of exercise for cardiovascular health are well documented. A review from Circulation published in 2003 summarized the benefits of regular physical activity on measures of cardiovascular health including reduction in body weight, blood pressure, and bad cholesterol, while increasing insulin sensitivity, good cholesterol, and muscular strength and function. In that review, author Jonathan N. Myers, PhD, now of Stanford (Calif.) University, noted that “one need not be a marathon runner or an elite athlete to derive significant benefits from physical activity.” In fact, “the greatest gains in terms of mortality are achieved when an individual goes from being sedentary to becoming moderately active.”
A recent large, population-based study showed the value of short bursts of exercise for those previously sedentary. In this study, published in Nature Medicine, a team in Australia used wearable fitness trackers to measure the health benefits of what researchers have named “vigorous intermittent lifestyle physical activity” or VILPA.
Some examples of VILPA include power walking on the way to work, climbing stairs, or even running around with your kids on the playground.
Specifically, individuals who engaged in the median VILPA frequency of three bursts of vigorous activity lasting 1-2 minutes showed a 38%-40% reduction in all-cause mortality risk and cancer mortality risk, and a 48%-49% reduction in cardiovascular mortality risk.
The researchers repeated their analysis for a group of 62,344 adults from the UK Biobank who reported regular vigorous physical activity (VPA). They found similar effects on mortality, based on 1,552 deaths reported.
These results suggest that VILPA may be a reasonable physical activity target, especially for people not able or willing to exercise more formally or intensely, the researchers noted.
“We have known for a long time that leisure-time exercise often reaches vigorous intensity and has many health benefits, but we understand less about the health potential of daily movement, especially activities done as part of daily living that reach vigorous intensity,” lead author Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle and population health at the University of Sydney’s Charles Perkins Centre, said in an interview.
“As long as the heart rate goes up for a minute or 2 it will likely be vigorous activity,” Dr. Stamatakis said in an interview. “It is also important that clinicians effectively communicate how patients can know that they are reaching vigorous intensity,” he said.
Signs of vigorous intensity include increased heart rate and getting out of breath after about 20-40 seconds from the start of the VILPA burst. After about a minute of VILPA, the person doing it should be too out of breath to speak more than a few words comfortably, he said.
Data support value of any and all exercise
The Nature Medicine study supports other recent research showing the value of short, intense bursts of physical activity. A pair of recent studies also used fitness trackers to measure activity in adults and assess the benefits on outcomes including death and heart disease.
One of these studies, which was published in the European Heart Journal, also used fitness trackers to measure physical activity at moderate and vigorous levels. The researchers found that individuals who performed at least 20% of their physical activity at a moderate to high level, such as by doing brisk walking in lieu of strolling had a significantly lower risk of heart disease than those whose daily activity included less than 20% at a moderate or intense level.
In another study from the European Heart Journal, researchers found that short bursts of vigorous physical activity of 2 minutes or less adding up to 15-20 minutes per week was enough to reduce mortality by as much as 40%.
Plus, a meta-analysis published in the Lancet showed a decrease in all-cause mortality with an increase in the number of daily steps, although the impact of stepping rate on mortality was inconsistent.
“Many studies have investigated the health benefits of physical activity, but not the importance of these difficult-to-capture VILPA bouts that accrue during the course of normal activities of daily living,” Lee Stoner, PhD, an exercise physiologist and director of the Cardiometabolic Lab at the University of North Carolina at Chapel Hill, said in an interview.
Dr. Stoner, who was not involved in the Nature Medicine study, said he was not surprised by the overall finding that doing short bursts of activity impacted mortality and cardiovascular disease, but was slightly surprised by the strength of the evidence.
“The referent group in the Nature Medicine study were those accruing no VILPA”, likely meaning they were very inactive,” Dr. Stoner said and added that he thinks this demonstrates the value of VILPA.
Even without immediately meeting the specific numbers recommended by the CDC, “any physical activity is better than none, especially if vigorous, and VILPA can be built into normal daily routines,” Dr. Stoner added.
What’s missing in short bursts?
Short bursts of activity do have their limits when it comes to overall fitness, said Dr. Stoner.
“Endurance will not be improved as much through short bursts, because such activities are unlikely to be as effective at empowering the mitochondria – the batteries keeping our cells running, including skeletal muscle cells,” he said. “Additionally, the vigorous bouts are unlikely to be as effective at improving muscular strength and endurance. For this, it is recommended that we engage each muscle group in strengthening exercises two times per week.”
However, Dr. Stoner agreed that prescribing short bursts of intense activity as part of daily living may be a great way to get people started with exercise.
“The key is to remove barriers to physical activity pursuit, then focusing on long-term routine rather than short-term gain,” he said. “Individuals are better served if they focus on goals other than weight loss, for which physical activity or exercise may not be the solution. Rather, being physically active can improve vigor, make daily activities simpler, and improve cognitive abilities,” and any physical activity is one of the most effective solutions for regulating blood glucose levels and improving cardiovascular risk factors.
Make it routine – and fun
To benefit from physical activity, cultivating and sustaining a long-term routine is key, said Dr. Stoner, whose research has focused on sedentary behavior and cardiovascular disease. Whatever the activity is, shorter bursts, or longer bouts or both, it is essential that individuals figure out activities that they enjoy if they want to create sustained behavior, and thus health change, Gabriel Zieff, MA, a doctoral candidate in Dr. Stoner’s Cardiometabolic Lab, who conducts studies on exercise, noted in an interview.
“We exercise enthusiasts and researchers are often hyperfocused on whether this duration or that duration is better, whether this intensity or that intensity is better,” but at the end of the day, it is the enjoyment factor that often predicts sustained behavior change, and should be part of discussions with patients to help reduce sedentary behavior and promote activity, Mr. Zieff said.
Short bouts can encourage hesitant exercisers
“To best support health, clinicians should consider taking a few seconds to ask patients about their physical activity levels,” said Dr. Paluch, who was the lead author on the Lancet meta-analysis of daily steps. In that study, Dr. Paluch and colleagues found that taking more steps each day was associated with a progressively lower risk of all-cause mortality. However, that study did not measure step rate.
Clinicians can emphasize that health benefits do not require an hour-long exercise routine and special equipment, and moving more, even in shorts bursts of activity can have meaningful associations with health, particularly for those who are less active, she said.
The recent studies on short bursts of activity agree that “some physical activity is better than none and adults should move more throughout the day in whatever way makes sense to them and fits best into their lives,” said Dr. Paluch. “For example, opting for the stairs instead of the elevator, a brisk walk to the bus stop, a short game of hide and seek with the children or grandchildren – anything that gets your body moving more, even if briefly. Making simple lifestyle changes is often easier in small bites. In time, this can grow into long-term habits, ultimately leading to an overall active lifestyle that supports living healthier for longer.”
The Nature Medicine study was supported by the Australian National Health and Medical Research Council. Several coauthors were supported by the Wellcome Trust, the National Institute for Health Research Oxford Biomedical Research Centre, Novo Nordisk, the British Heart Foundation Centre of Research Excellence, the Alan Turing Institute, the British Heart Foundation, and Health Data Research UK, an initiative funded by UK Research and Innovation. Dr. Paluch and Dr. Stoner had no financial conflicts to disclose.
Fitbit figures: More steps per day cut type 2 diabetes risk
The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.
Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.
“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
Despite low baseline risk, benefit from increased physical activity
The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m2). Three quarters were women and 89% were White.
It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.
The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.
The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).
“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
Physical activity tracked over close to 4 years
Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.
The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.
From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.
The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).
During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.
They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.
The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).
“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.
This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.
A version of this article first appeared on Medscape.com.
The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.
Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.
“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
Despite low baseline risk, benefit from increased physical activity
The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m2). Three quarters were women and 89% were White.
It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.
The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.
The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).
“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
Physical activity tracked over close to 4 years
Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.
The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.
From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.
The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).
During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.
They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.
The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).
“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.
This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.
A version of this article first appeared on Medscape.com.
The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.
Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.
“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
Despite low baseline risk, benefit from increased physical activity
The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m2). Three quarters were women and 89% were White.
It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.
The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.
The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).
“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
Physical activity tracked over close to 4 years
Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.
The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.
From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.
The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).
During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.
They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.
The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).
“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.
This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.
A version of this article first appeared on Medscape.com.
Rise of ‘alarming’ subvariants of COVID ‘worrisome’ for winter
It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications.
Not too dire so far, until the researchers’ other findings are considered.
The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.
On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.
What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.
But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.
Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.
In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age.
It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.
Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.
“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
An evolving virus
The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”
BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.
The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”
To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.
Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.
The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.
This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
Wiping out treatments too
Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.
They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.
This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.
The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”
A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.
Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.
Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.
In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”
A version of this article first appeared on Medscape.com.
It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications.
Not too dire so far, until the researchers’ other findings are considered.
The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.
On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.
What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.
But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.
Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.
In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age.
It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.
Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.
“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
An evolving virus
The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”
BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.
The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”
To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.
Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.
The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.
This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
Wiping out treatments too
Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.
They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.
This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.
The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”
A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.
Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.
Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.
In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”
A version of this article first appeared on Medscape.com.
It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications.
Not too dire so far, until the researchers’ other findings are considered.
The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.
On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.
What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.
But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.
Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.
In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age.
It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.
Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.
“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
An evolving virus
The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”
BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.
The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”
To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.
Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.
The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.
This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
Wiping out treatments too
Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.
They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.
This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.
The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”
A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.
Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.
Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.
In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”
A version of this article first appeared on Medscape.com.
FROM CELL
Guidance updated for congenital hypothyroidism screening, management
Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.
Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).
Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.
In addition to screening, timely diagnosis, effective treatment, and follow-up are important.
Tests don’t always tell the full story with congenital hypothyroidism.
“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.
They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.
Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.
Following are highlights of the guidance:
Clinical signs
Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.
Newborn screening in first days
Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.
Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.
The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.
That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.
“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.
If a newborn infant is transferred to another hospital, communication about the screening is critical.
Testing strategies
Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.
“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.
Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
Multiple births, same-sex twins
The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.
“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
Down syndrome
Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.
Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).
“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
Communication with primary care provider
Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.
Serum confirmation after abnormal screening
The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.
For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
Interpreting serum confirmation
Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.
But there are various other outcomes with more controversy.
Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.
In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.
“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.
Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.
“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
Imaging
Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.
Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.
“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.
Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
Treatment
Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.
L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.
An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.
“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.
The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.
Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.
“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
Monitoring
In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.
In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
Developmental outcomes
When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.
In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.
“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”
If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.
The authors report no relevant financial relationships.
Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.
Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).
Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.
In addition to screening, timely diagnosis, effective treatment, and follow-up are important.
Tests don’t always tell the full story with congenital hypothyroidism.
“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.
They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.
Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.
Following are highlights of the guidance:
Clinical signs
Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.
Newborn screening in first days
Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.
Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.
The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.
That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.
“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.
If a newborn infant is transferred to another hospital, communication about the screening is critical.
Testing strategies
Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.
“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.
Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
Multiple births, same-sex twins
The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.
“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
Down syndrome
Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.
Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).
“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
Communication with primary care provider
Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.
Serum confirmation after abnormal screening
The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.
For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
Interpreting serum confirmation
Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.
But there are various other outcomes with more controversy.
Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.
In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.
“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.
Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.
“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
Imaging
Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.
Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.
“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.
Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
Treatment
Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.
L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.
An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.
“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.
The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.
Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.
“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
Monitoring
In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.
In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
Developmental outcomes
When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.
In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.
“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”
If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.
The authors report no relevant financial relationships.
Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.
Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).
Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.
In addition to screening, timely diagnosis, effective treatment, and follow-up are important.
Tests don’t always tell the full story with congenital hypothyroidism.
“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.
They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.
Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.
Following are highlights of the guidance:
Clinical signs
Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.
Newborn screening in first days
Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.
Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.
The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.
That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.
“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.
If a newborn infant is transferred to another hospital, communication about the screening is critical.
Testing strategies
Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.
“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.
Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
Multiple births, same-sex twins
The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.
“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
Down syndrome
Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.
Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).
“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
Communication with primary care provider
Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.
Serum confirmation after abnormal screening
The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.
For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
Interpreting serum confirmation
Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.
But there are various other outcomes with more controversy.
Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.
In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.
“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.
Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.
“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
Imaging
Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.
Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.
“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.
Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
Treatment
Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.
L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.
An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.
“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.
The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.
Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.
“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
Monitoring
In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.
In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
Developmental outcomes
When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.
In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.
“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”
If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.
The authors report no relevant financial relationships.
FROM PEDIATRICS