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Early transition to oral beta-lactams for low-risk S. aureus bacteremia may be acceptable
Background: There is consensus that LR-SAB can be safely treated with 14 days of antibiotic therapy, but the use of and/or proportion of duration of oral antibiotics is not clear. There is evidence that oral therapy has fewer treatment complications, compared with IV treatments. Objective of this study was to assess the safety of early oral switch (EOS) prior to 14 days for LR-SAB.
Study design: Retrospective cohort study.
Setting: Single institution tertiary care hospital in Wellington, New Zealand.
Synopsis: Study population included adults with health care–associated SAB deemed low risk (no positive blood cultures >72 hours after initial positive culture, no evidence of deep infection as determined by an infectious disease consultant, no nonremovable prosthetics). The primary outcome was occurrence of SAB-related complication (recurrence of SAB, deep-seated infection, readmission, attributable mortality) within 90 days.
Of the initial 469 episodes of SAB, 100 met inclusion, and 84 of those patients had EOS. Line infection was the source in a majority of patients (79% and 88% in EOS and IV, respectively). Only 5% of patients had MRSA. Overall, 86% of EOS patients were treated with an oral beta-lactam, within the EOS group, median duration of IV and oral antibiotics was 5 and 10 days, respectively. SAB recurrence within 90 days occurred in three (4%) and one (6%) patients in EOS vs. IV groups, respectively (P = .64). No deaths within 90 days were deemed attributable to SAB. Limitations include small size, single center, and observational, retrospective framework.
Bottom line: The study suggests that EOS with oral beta-lactams in selected patients with LR-SAB may be adequate; however, the study is too small to provide robust high-level evidence. Instead, the authors hope the data will lead to larger, more powerful prospective studies to examine if a simpler, cheaper, and in some ways safer treatment course is possible.
Citation: Bupha-Intr O et al. Efficacy of early oral switch with beta-lactams for low-risk Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2020 Feb 3;AAC.02345-19. doi: 10.1128/AAC.02345-19.
Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Background: There is consensus that LR-SAB can be safely treated with 14 days of antibiotic therapy, but the use of and/or proportion of duration of oral antibiotics is not clear. There is evidence that oral therapy has fewer treatment complications, compared with IV treatments. Objective of this study was to assess the safety of early oral switch (EOS) prior to 14 days for LR-SAB.
Study design: Retrospective cohort study.
Setting: Single institution tertiary care hospital in Wellington, New Zealand.
Synopsis: Study population included adults with health care–associated SAB deemed low risk (no positive blood cultures >72 hours after initial positive culture, no evidence of deep infection as determined by an infectious disease consultant, no nonremovable prosthetics). The primary outcome was occurrence of SAB-related complication (recurrence of SAB, deep-seated infection, readmission, attributable mortality) within 90 days.
Of the initial 469 episodes of SAB, 100 met inclusion, and 84 of those patients had EOS. Line infection was the source in a majority of patients (79% and 88% in EOS and IV, respectively). Only 5% of patients had MRSA. Overall, 86% of EOS patients were treated with an oral beta-lactam, within the EOS group, median duration of IV and oral antibiotics was 5 and 10 days, respectively. SAB recurrence within 90 days occurred in three (4%) and one (6%) patients in EOS vs. IV groups, respectively (P = .64). No deaths within 90 days were deemed attributable to SAB. Limitations include small size, single center, and observational, retrospective framework.
Bottom line: The study suggests that EOS with oral beta-lactams in selected patients with LR-SAB may be adequate; however, the study is too small to provide robust high-level evidence. Instead, the authors hope the data will lead to larger, more powerful prospective studies to examine if a simpler, cheaper, and in some ways safer treatment course is possible.
Citation: Bupha-Intr O et al. Efficacy of early oral switch with beta-lactams for low-risk Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2020 Feb 3;AAC.02345-19. doi: 10.1128/AAC.02345-19.
Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Background: There is consensus that LR-SAB can be safely treated with 14 days of antibiotic therapy, but the use of and/or proportion of duration of oral antibiotics is not clear. There is evidence that oral therapy has fewer treatment complications, compared with IV treatments. Objective of this study was to assess the safety of early oral switch (EOS) prior to 14 days for LR-SAB.
Study design: Retrospective cohort study.
Setting: Single institution tertiary care hospital in Wellington, New Zealand.
Synopsis: Study population included adults with health care–associated SAB deemed low risk (no positive blood cultures >72 hours after initial positive culture, no evidence of deep infection as determined by an infectious disease consultant, no nonremovable prosthetics). The primary outcome was occurrence of SAB-related complication (recurrence of SAB, deep-seated infection, readmission, attributable mortality) within 90 days.
Of the initial 469 episodes of SAB, 100 met inclusion, and 84 of those patients had EOS. Line infection was the source in a majority of patients (79% and 88% in EOS and IV, respectively). Only 5% of patients had MRSA. Overall, 86% of EOS patients were treated with an oral beta-lactam, within the EOS group, median duration of IV and oral antibiotics was 5 and 10 days, respectively. SAB recurrence within 90 days occurred in three (4%) and one (6%) patients in EOS vs. IV groups, respectively (P = .64). No deaths within 90 days were deemed attributable to SAB. Limitations include small size, single center, and observational, retrospective framework.
Bottom line: The study suggests that EOS with oral beta-lactams in selected patients with LR-SAB may be adequate; however, the study is too small to provide robust high-level evidence. Instead, the authors hope the data will lead to larger, more powerful prospective studies to examine if a simpler, cheaper, and in some ways safer treatment course is possible.
Citation: Bupha-Intr O et al. Efficacy of early oral switch with beta-lactams for low-risk Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2020 Feb 3;AAC.02345-19. doi: 10.1128/AAC.02345-19.
Dr. Sneed is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Inflammatory diet is linked to dementia
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
‘A few mutations away’: The threat of a vaccine-proof variant
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
Prevalence of dementia before age 65 much higher than expected
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
‘Shocking’ early complications from teen-onset type 2 diabetes
Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.
The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.
At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.
At this time, more than two thirds had hypertension and half had dyslipidemia.
Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.
“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
Don’t tread lightly just because they are young
“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.
“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.
“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”
Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.
New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.
“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.
And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
Follow-up shows all metrics worsening over time
In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.
Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.
The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.
At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.
The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.
Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.
Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
Serious cardiovascular events in mid-20s
There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.
Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.
Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.
“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
Findings have multiple causes
The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.
“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.
“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”
It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”
He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”
The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.
A version of this article first appeared on Medscape.com.
Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.
The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.
At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.
At this time, more than two thirds had hypertension and half had dyslipidemia.
Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.
“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
Don’t tread lightly just because they are young
“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.
“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.
“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”
Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.
New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.
“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.
And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
Follow-up shows all metrics worsening over time
In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.
Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.
The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.
At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.
The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.
Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.
Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
Serious cardiovascular events in mid-20s
There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.
Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.
Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.
“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
Findings have multiple causes
The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.
“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.
“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”
It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”
He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”
The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.
A version of this article first appeared on Medscape.com.
Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said the researchers.
The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 29 in the New England Journal of Medicine by the TODAY study group.
At follow-up – after originally participating in the TODAY trial when they were young teenagers – they had a mean age of 26.4 years.
At this time, more than two thirds had hypertension and half had dyslipidemia.
Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications.
“These data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood,” the researchers noted.
Don’t tread lightly just because they are young
“The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, said in an interview.
“In the absence of studies specifically addressing this, we need to take a more aggressive approach than people might be inclined to, given that the age at diagnosis is young, around 14 years,” he added.
“Contrary to the inclination to be ‘gentle’ in treating them because they are kids, these data suggest that we can’t let these initial years go by without strong intervention, and we need to be prepared for polypharmacy.”
Unfortunately, as Dr. Zeitler and coauthors explained, youth-onset type 2 diabetes is characterized by a suboptimal response to currently approved diabetes medications.
New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval of extended-release exenatide for children as young as 10 years of age, “helps, but only marginally,” said Dr. Zeitler, of the Clinical & Translational Research Center, Children’s Hospital Colorado, Aurora.
“In some cases, it will help get them covered by carriers, which is always good. But this is still a very limited set of medications. It doesn’t include more recently approved more potent glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, and doesn’t include the sodium-glucose cotransporter 2 (SGLT2) inhibitors. Pediatricians are used to using medications off label and that is necessary here while we await further approvals,” he said.
And he noted that most individuals with youth-onset type 2 diabetes in the United States are covered by public insurance or are uninsured, depending on which state they live in. While the two major Medicaid programs in Colorado allow full access to adult formularies, that’s not the case everywhere. Moreover, patients often face further access barriers in states without expanded Medicaid.
Follow-up shows all metrics worsening over time
In TODAY 2, patients participated in an observational follow-up in their usual care settings in 2011-2020. At the start, they were receiving metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors was down to individual circumstances.
Participants’ median A1c increased over time, and the percentage with A1c < 6% (< 48 mmol/mol) declined from 75% at the time of TODAY entry to just 19% at the 15-year end of follow-up.
The proportion with an A1c ≤ 10% (≤ 86 mmol/mol) rose from 0% at baseline to 34% at 15 years.
At that time, nearly 50% were taking both metformin and insulin, while more than a quarter were taking no medications.
The prevalence of hypertension increased from 19.2% at baseline to 67.5% at 15 years, while dyslipidemia rose from 20.8% to 51.6%.
Kidney disease prevalence increased from 8.0% at baseline to 54.8% at 15 years. Nerve disease rose from 1.0% to 32.4%. Retinal disease jumped from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.
Overall, at the time of the last visit, 39.9% had no diabetes complications, 31.8% had one, 21.3% had two, and 7.1% had three complications.
Serious cardiovascular events in mid-20s
There were 17 adjudicated serious cardiovascular events, including four myocardial infarctions, six heart failure events, three diagnoses of coronary artery disease, and four strokes.
Six participants died, one each from myocardial infarction, kidney failure, and drug overdose, and three from sepsis.
Dr. Zeitler called the macrovascular events “shocking,” noting that although the numbers are small, for people in their mid-20s “they should be zero ... While we don’t yet know if the rates are the same or faster than in adults, even if they are the same, these kids are only in their late 20s, as opposed to adults experiencing these problems in their 50s, 60s, and 70s.
“The fact that these complications are occurring when these individuals should be in the prime of their life for both family and work has huge implications,” he stressed.
Findings have multiple causes
The reasons for the findings are both biologic and socioeconomic, Dr. Zeitler said.
“We know already that many kids with type 2 have rapid [deterioration of] beta-cell [function], which is probably very biologic. It stands to reason that an individual who can get diabetes as an adolescent probably has more fragile beta cells in some way,” he noted.
“But we also know that many other things contribute: stress, social determinants, access to quality care and medications, access to healthy foods and physical activity, availability of family supervision given the realities of families’ economic status and jobs, etc.”
It’s also known that youth with type 2 diabetes have much more severe insulin resistance than that of adults with the condition, and that “once the kids left ... the [TODAY] study, risk factor treatment in the community was less than ideal, and a lot of kids who met criteria for treatment of their blood pressure or lipids were not being treated. This is likely at least partly sociologic and partly the general pediatric hesitancy to use medications.”
He said the TODAY team will soon have some new data to show that “glycemia during the early years makes a difference, again supporting intensive intervention early on.”
The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler had no further disclosures.
A version of this article first appeared on Medscape.com.
COVID-19 leaves wake of medical debt among U.S. adults
Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.
The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.
For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.
“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.
“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.
Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.
Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.
“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.
When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.
According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.
George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.
“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”
He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.
“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”
For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.
Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.
“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”
Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.
A version of this article first appeared on Medscape.com.
Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.
The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.
For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.
“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.
“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.
Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.
Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.
“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.
When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.
According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.
George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.
“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”
He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.
“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”
For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.
Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.
“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”
Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.
A version of this article first appeared on Medscape.com.
Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.
The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.
For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.
“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.
“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.
Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.
Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.
“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.
When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.
According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.
George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.
“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”
He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.
“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”
For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.
Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.
“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”
Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.
A version of this article first appeared on Medscape.com.
Vaccinated people infected with Delta remain contagious
, The New York Times reported late on July 29.
The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.
The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the Times said. The bottom line is that the CDC data show people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.
ABC News reported earlier on July 29 that the CDC’s updated mask guidance followed an outbreak in Cape Cod, where crowds gathered for the Fourth of July.
As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.
, The New York Times reported late on July 29.
The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.
The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the Times said. The bottom line is that the CDC data show people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.
ABC News reported earlier on July 29 that the CDC’s updated mask guidance followed an outbreak in Cape Cod, where crowds gathered for the Fourth of July.
As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.
, The New York Times reported late on July 29.
The revelation is one reason the agency reversed course this week and said fully vaccinated people should go back to wearing masks in many cases.
The new findings also are a reversal from what scientists had believed to be true about other variants of the virus, the Times said. The bottom line is that the CDC data show people with so-called breakthrough cases of the Delta variant may be just as contagious as unvaccinated people, even if they do not show symptoms.
ABC News reported earlier on July 29 that the CDC’s updated mask guidance followed an outbreak in Cape Cod, where crowds gathered for the Fourth of July.
As of July 29, 882 people were tied to the outbreak centered in Provincetown, Mass. Of those who live in Massachusetts, 74% were unvaccinated. ABC said the majority were showing symptoms of COVID-19.
Study highlights impact of acne in adult women on quality of life, mental health
results from a qualitative study demonstrated.
“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”
For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.
The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).
More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.
In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.
“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”
In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”
Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”
In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”
A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”
For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”
This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.
results from a qualitative study demonstrated.
“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”
For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.
The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).
More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.
In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.
“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”
In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”
Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”
In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”
A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”
For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”
This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.
results from a qualitative study demonstrated.
“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”
For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.
The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).
More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.
In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.
“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”
In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”
Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”
In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”
A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”
For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”
This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.
FROM JAMA DERMATOLOGY
Hyperimmune globulin fails to prevent congenital CMV infection
Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.
Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.
Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.
“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”
The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.
The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).
When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.
One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.
“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.
“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.
Other experts agree that developing a vaccine should be the priority.
“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.
“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.
Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.
Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.
“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.
“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”
The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.
A version of this article first appeared on Medscape.com.
Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.
Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.
Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.
“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”
The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.
The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).
When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.
One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.
“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.
“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.
Other experts agree that developing a vaccine should be the priority.
“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.
“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.
Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.
Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.
“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.
“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”
The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.
A version of this article first appeared on Medscape.com.
Administering hyperimmune globulin to pregnant women who tested positive for cytomegalovirus did not reduce CMV infections or deaths among their fetuses or newborns, according to a randomized controlled trial published online July 28 in the New England Journal of Medicine.
Up to 40,000 infants a year have congenital CMV infections, which can lead to stillbirth, neonatal death, deafness, and cognitive and motor delay. An estimated 35%-40% of fetuses of women with a primary CMV infection will develop an infection, write Brenna Hughes, MD, an associate professor of ob/gyn and chief of the division of maternal fetal medicine at Duke University, Durham, N.C., and colleagues.
Previous trials and observational studies have shown mixed results with hyperimmune globulin for the prevention of congenital CMV infection.
“It was surprising to us that none of the outcomes in this trial were in the direction of potential benefit,” Dr. Hughes told this news organization. “However, this is why it is important to do large trials in a diverse population.”
The study cohort comprised 206,082 pregnant women who were screened for CMV infection before 23 weeks’ gestation. Of those women, 712 (0.35%) tested positive for CMV. The researchers enrolled 399 women who had tested positive and randomly assigned them to receive either a monthly infusion of CMV hyperimmune globulin (100 mg/kg) or placebo until delivery. The researchers used a composite of CMV infection or, if no testing occurred, fetal/neonatal death as the primary endpoint.
The trial was stopped early for futility when data from 394 participants revealed that 22.7% of offspring in the hyperimmune globulin group and 19.4% of those in the placebo group had had a CMV infection or had died (relative risk = 1.17; P = .42).
When individual endpoints were examined, trends were detected in favor of the placebo, but they did not reach statistical significance. The incidence of death was higher in the hyperimmune globulin group (4.9%) than in the placebo group (2.6%). The rate of preterm birth was also higher in the intervention group (12.2%) than in the group that received placebo (8.3%). The incidence of birth weight below the fifth percentile was 10.3% in the intervention group and 5.4% in the placebo group.
One woman who received hyperimmune globulin experienced a severe allergic reaction to the first infusion. Additionally, more women in the hyperimmune globulin group experienced headaches and shaking chills during infusions than did those who received placebo. There were no differences in maternal outcomes between the groups. There were no thromboembolic or ischemic events in either group.
“These findings suggest CMV hyperimmune globulin should not be used for the prevention of congenital CMV in pregnant patients with primary CMV during pregnancy,” Dr. Hughes said in an interview.
“A CMV vaccine is likely to be the most effective public health measure that we can offer, and that should be at the forefront of research investments,” she said. “But some of the other medications that work against CMV should be tested on a large scale as well,” she said. For example, a small trial in Israel showed that high-dose valacyclovir in early pregnancy decreased congenital CMV, and thus the drug merits study in a larger trial, she said.
Other experts agree that developing a vaccine should be the priority.
“The ultimate goal for preventing the brain damage and birth defects caused by congenital CMV infection is a vaccine that is as effective as the rubella vaccine has been for eliminating congenital rubella syndrome and that can be given well before pregnancy,” said Sallie Permar, MD, PhD, chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at New York–Presbyterian/Weill Cornell Medical Center and the New York–Presbyterian Komansky Children’s Hospital in New York.
“While trials of vaccines are ongoing, there is a need to have a therapeutic option, especially for the high-risk setting of a mother acquiring the virus for the first time during pregnancy,” Dr. Permar said in an interview.
Dr. Permar was not involved in this study but is involved in follow-up studies of this cohort and is conducting research on CMV maternal vaccines. She noted the need for safe, effective antiviral treatments and for research into newer immunoglobulin products, such as monoclonal antibodies.
Both Dr. Permar and Dr. Hughes highlighted the challenge of raising awareness about the danger of CMV infections during pregnancy.
“Pregnant women, and especially those who have or work with young children, who are frequently carriers of the infection, should be informed of this risk,” Dr. Permar said. She hopes universal testing of newborns will be implemented and that it enables people to recognize the frequency and burden of these infections. She remains optimistic about a vaccine.
“After 60 years of research into a CMV vaccine, I believe we are currently in a ‘golden age’ of CMV vaccine development,” she said. She noted that Moderna is about to launch a phase 3 mRNA vaccine trial for CMV. “Moreover, immune correlates of protection against CMV have been identified from previous partially effective vaccines, and animal models have improved for preclinical studies. Therefore, I believe we will have an effective and safe vaccine against this most common congenital infection in the coming years.”
The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Dr. Hughes has served on Merck’s scientific advisory board. Various coauthors have received personal fees from Medela and nonfinancial support from Hologic; personal fees from Moderna and VBI vaccines, and grants from Novavax. Dr. Permar consults for Pfizer, Moderna, Merck, Sanofi, and Dynavax on their CMV vaccine programs, and she has a sponsored research program with Merck and Moderna on CMV vaccines.
A version of this article first appeared on Medscape.com.
Traumatic Fractures Should Trigger Osteoporosis Assessment in Postmenopausal Women
Study Overview
Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.
Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.
Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.
Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.
Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.
Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.
Commentary
Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.1 It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.1
The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.1 In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.2 This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.
Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.
Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.1 However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.3 Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.4 Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.
The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.
Applications for Clinical Practice
The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.
1. US Preventive Services Task Force, Curry SJ, Krist Ah, et al. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319(24):2521–2531. doi:10.1001/jama.2018.7498
2. Crandall CJ, Larson JC, LaCroix AZ, et al. Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures. JAMA Intern Med. Published online June 7, 2021. doi:10.1001/jamainternmed.2021.2617
3. Mackey DC, Lui L, Cawthon PM, et al. High-Trauma Fractures and Low Bone Mineral Density in Older Women and Men. JAMA. 2007;298(20):2381–2388. doi:10.1001/jama.298.20.2381
4. Leslie WD, Schousboe JT, Morin SN, et al. Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study. Osteoporos Int. 2020;31(6):1059–1067. doi:10.1007/s00198-019-05274-2
Study Overview
Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.
Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.
Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.
Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.
Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.
Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.
Commentary
Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.1 It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.1
The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.1 In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.2 This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.
Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.
Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.1 However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.3 Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.4 Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.
The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.
Applications for Clinical Practice
The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.
Study Overview
Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.
Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.
Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.
Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.
Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.
Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.
Commentary
Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.1 It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.1
The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.1 In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.2 This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.
Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.
Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.1 However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.3 Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.4 Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.
The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.
Applications for Clinical Practice
The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.
1. US Preventive Services Task Force, Curry SJ, Krist Ah, et al. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319(24):2521–2531. doi:10.1001/jama.2018.7498
2. Crandall CJ, Larson JC, LaCroix AZ, et al. Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures. JAMA Intern Med. Published online June 7, 2021. doi:10.1001/jamainternmed.2021.2617
3. Mackey DC, Lui L, Cawthon PM, et al. High-Trauma Fractures and Low Bone Mineral Density in Older Women and Men. JAMA. 2007;298(20):2381–2388. doi:10.1001/jama.298.20.2381
4. Leslie WD, Schousboe JT, Morin SN, et al. Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study. Osteoporos Int. 2020;31(6):1059–1067. doi:10.1007/s00198-019-05274-2
1. US Preventive Services Task Force, Curry SJ, Krist Ah, et al. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319(24):2521–2531. doi:10.1001/jama.2018.7498
2. Crandall CJ, Larson JC, LaCroix AZ, et al. Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures. JAMA Intern Med. Published online June 7, 2021. doi:10.1001/jamainternmed.2021.2617
3. Mackey DC, Lui L, Cawthon PM, et al. High-Trauma Fractures and Low Bone Mineral Density in Older Women and Men. JAMA. 2007;298(20):2381–2388. doi:10.1001/jama.298.20.2381
4. Leslie WD, Schousboe JT, Morin SN, et al. Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study. Osteoporos Int. 2020;31(6):1059–1067. doi:10.1007/s00198-019-05274-2