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FDA’s fast-track approval process exposed as lax, in need of reform
an in-depth investigation published in The BMJ has determined.
“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.
The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
Required studies rarely completed
As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.
However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.
The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.
In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.
Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.
For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.
As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.
Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.
“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
Call for reform
As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.
In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.
“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.
In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.
Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.
One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.
“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.
An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”
“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.
A version of this article first appeared on Medscape.com.
an in-depth investigation published in The BMJ has determined.
“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.
The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
Required studies rarely completed
As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.
However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.
The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.
In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.
Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.
For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.
As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.
Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.
“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
Call for reform
As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.
In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.
“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.
In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.
Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.
One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.
“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.
An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”
“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.
A version of this article first appeared on Medscape.com.
an in-depth investigation published in The BMJ has determined.
“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.
The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
Required studies rarely completed
As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.
However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.
The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.
In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.
Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.
For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.
As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.
Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.
“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
Call for reform
As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.
In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.
“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.
In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.
Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.
One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.
“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.
An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”
“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.
A version of this article first appeared on Medscape.com.
‘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.
‘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.
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.
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.
Can a supplement that mimics the keto diet reduce seizures?
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
early research suggests. However, at least one expert has concerns.
In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.
Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.
“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.
Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.
The findings were published online July 23, 2021, in Brain Communications.
Key ingredients
In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.
Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.
He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.
Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.
Dr. Walker noted that ketones are necessary in order to reduce seizures.
“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.
The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
Assessing feasibility
The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.
All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.
The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.
Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.
Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.
Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.
The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
Highly acceptable to patients
Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”
The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.
There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.
Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.
About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
50% seizure reduction
Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.
Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.
He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.
Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
Study concerns
Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.
Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.
However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.
Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.
“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.
Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”
The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.
A version of this article first appeared on Medscape.com.
FROM BRAIN COMMUNICATION
As common respiratory viruses resurface, children are at serious risk
Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.
The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.
“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”
The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.
In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.
Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.
“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”
Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.
“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.
Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.
“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”
A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.
Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.
“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”
Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.
However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.
He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.
“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”
To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.
Dr. Harrison and Dr. Webby reported no conflicts of interest.
Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.
The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.
“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”
The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.
In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.
Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.
“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”
Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.
“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.
Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.
“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”
A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.
Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.
“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”
Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.
However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.
He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.
“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”
To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.
Dr. Harrison and Dr. Webby reported no conflicts of interest.
Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.
The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.
“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”
The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.
In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.
Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.
“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”
Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.
“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.
Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.
“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”
A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.
Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.
“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”
Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.
However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.
He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.
“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”
To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.
Dr. Harrison and Dr. Webby reported no conflicts of interest.
Pfizer vaccine protection wanes after 6 months, study finds
, according to a new study.
The July 28 preprint report of the study, which has not been peer reviewed, suggests a gradual “declining trend in vaccine efficacy” over 6 months after two doses of the Pfizer vaccine in more than 45,000 people worldwide.
The study finds overall effectiveness falls from 96% to 84%.
At the same time, a third booster dose of the Pfizer vaccine increases neutralizing antibody levels against the Delta variant by more than five times, compared to levels after just a second dose in people aged 18-55 years, new data from Pfizer shows.
The third-dose immune response appears even more robust – more than 11 times higher than the second shot – among people aged 65-85 years.
The company noted this could mean an estimated 100-fold increase in Delta variant protection after a third dose. These new findings are outlined in a Pfizer second-quarter 2021 earnings report, which notes that the data are submitted for publication in a medical journal.
The data come from a relatively small number of people studied. There were 11 people in the 18- to 55-year-old group and 12 people in the 65- to 85-year-old group.
“These preliminary data are very encouraging as Delta continues to spread,” Mikael Dolsten, MD, chief scientific officer and president of the Worldwide Research, Development, and Medical organization at Pfizer, said during prepared remarks on a company earnings call July 28, CNN reported.
Availability of a third dose of any of the current COVID-19 vaccines would require amendment of the Food and Drug Administration’s emergency use authorization, or full FDA approval for the vaccine.
The possibility of a third dose authorization or approval has not been without controversy. For example, when Pfizer announced intentions to file for FDA authorization of a booster dose on July 8, the Centers for Disease Control and Prevention, the FDA, and the National Institutes of Health were quick to issue a joint statement saying they would decide when the timing is right for Americans to have a third immunization. The agencies stated, in part, “We are prepared for booster doses if and when the science demonstrates that they are needed.”
In addition, the World Health Organization said at a media briefing on July 12 that rich countries should prioritize sharing of COVID-19 vaccine supplies to other countries in need worldwide before allocating doses for a booster shot for its own residents.
A version of this article first appeared on WebMD.com.
, according to a new study.
The July 28 preprint report of the study, which has not been peer reviewed, suggests a gradual “declining trend in vaccine efficacy” over 6 months after two doses of the Pfizer vaccine in more than 45,000 people worldwide.
The study finds overall effectiveness falls from 96% to 84%.
At the same time, a third booster dose of the Pfizer vaccine increases neutralizing antibody levels against the Delta variant by more than five times, compared to levels after just a second dose in people aged 18-55 years, new data from Pfizer shows.
The third-dose immune response appears even more robust – more than 11 times higher than the second shot – among people aged 65-85 years.
The company noted this could mean an estimated 100-fold increase in Delta variant protection after a third dose. These new findings are outlined in a Pfizer second-quarter 2021 earnings report, which notes that the data are submitted for publication in a medical journal.
The data come from a relatively small number of people studied. There were 11 people in the 18- to 55-year-old group and 12 people in the 65- to 85-year-old group.
“These preliminary data are very encouraging as Delta continues to spread,” Mikael Dolsten, MD, chief scientific officer and president of the Worldwide Research, Development, and Medical organization at Pfizer, said during prepared remarks on a company earnings call July 28, CNN reported.
Availability of a third dose of any of the current COVID-19 vaccines would require amendment of the Food and Drug Administration’s emergency use authorization, or full FDA approval for the vaccine.
The possibility of a third dose authorization or approval has not been without controversy. For example, when Pfizer announced intentions to file for FDA authorization of a booster dose on July 8, the Centers for Disease Control and Prevention, the FDA, and the National Institutes of Health were quick to issue a joint statement saying they would decide when the timing is right for Americans to have a third immunization. The agencies stated, in part, “We are prepared for booster doses if and when the science demonstrates that they are needed.”
In addition, the World Health Organization said at a media briefing on July 12 that rich countries should prioritize sharing of COVID-19 vaccine supplies to other countries in need worldwide before allocating doses for a booster shot for its own residents.
A version of this article first appeared on WebMD.com.
, according to a new study.
The July 28 preprint report of the study, which has not been peer reviewed, suggests a gradual “declining trend in vaccine efficacy” over 6 months after two doses of the Pfizer vaccine in more than 45,000 people worldwide.
The study finds overall effectiveness falls from 96% to 84%.
At the same time, a third booster dose of the Pfizer vaccine increases neutralizing antibody levels against the Delta variant by more than five times, compared to levels after just a second dose in people aged 18-55 years, new data from Pfizer shows.
The third-dose immune response appears even more robust – more than 11 times higher than the second shot – among people aged 65-85 years.
The company noted this could mean an estimated 100-fold increase in Delta variant protection after a third dose. These new findings are outlined in a Pfizer second-quarter 2021 earnings report, which notes that the data are submitted for publication in a medical journal.
The data come from a relatively small number of people studied. There were 11 people in the 18- to 55-year-old group and 12 people in the 65- to 85-year-old group.
“These preliminary data are very encouraging as Delta continues to spread,” Mikael Dolsten, MD, chief scientific officer and president of the Worldwide Research, Development, and Medical organization at Pfizer, said during prepared remarks on a company earnings call July 28, CNN reported.
Availability of a third dose of any of the current COVID-19 vaccines would require amendment of the Food and Drug Administration’s emergency use authorization, or full FDA approval for the vaccine.
The possibility of a third dose authorization or approval has not been without controversy. For example, when Pfizer announced intentions to file for FDA authorization of a booster dose on July 8, the Centers for Disease Control and Prevention, the FDA, and the National Institutes of Health were quick to issue a joint statement saying they would decide when the timing is right for Americans to have a third immunization. The agencies stated, in part, “We are prepared for booster doses if and when the science demonstrates that they are needed.”
In addition, the World Health Organization said at a media briefing on July 12 that rich countries should prioritize sharing of COVID-19 vaccine supplies to other countries in need worldwide before allocating doses for a booster shot for its own residents.
A version of this article first appeared on WebMD.com.
Money buys life, and a cigarette maker wants to ‘unsmoke the world’
With COVID, the fun never ends
Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!
Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”
Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.
Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.
Joe: Sounds like communism to me, Tony. I’ll say Cuba.
Tony: Sorry Joe, that’s incorrect. Don?
Don: The friends and families sound like freedom-loving Americans, so it must be America.
Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?
Joe: That’s fake news, Tony. It’s gotta be false.
Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.
Don: That’s bulls#&@! I won this thing! I’ll see you in court!
More money, more life
Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.
Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.
“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.
But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.
We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
Holding the ‘health care and wellness’ gun
Cigarettes are not good for us. We know this.
It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.
Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.
And if those aren’t egregious business euphemisms, we don’t know what is.
Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?
So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.
Okay, we lied, it’s the second one.
Autopsy of the living dead
Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.
Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.
It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.
Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
With COVID, the fun never ends
Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!
Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”
Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.
Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.
Joe: Sounds like communism to me, Tony. I’ll say Cuba.
Tony: Sorry Joe, that’s incorrect. Don?
Don: The friends and families sound like freedom-loving Americans, so it must be America.
Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?
Joe: That’s fake news, Tony. It’s gotta be false.
Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.
Don: That’s bulls#&@! I won this thing! I’ll see you in court!
More money, more life
Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.
Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.
“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.
But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.
We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
Holding the ‘health care and wellness’ gun
Cigarettes are not good for us. We know this.
It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.
Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.
And if those aren’t egregious business euphemisms, we don’t know what is.
Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?
So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.
Okay, we lied, it’s the second one.
Autopsy of the living dead
Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.
Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.
It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.
Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
With COVID, the fun never ends
Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!
Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”
Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.
Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.
Joe: Sounds like communism to me, Tony. I’ll say Cuba.
Tony: Sorry Joe, that’s incorrect. Don?
Don: The friends and families sound like freedom-loving Americans, so it must be America.
Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?
Joe: That’s fake news, Tony. It’s gotta be false.
Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.
Don: That’s bulls#&@! I won this thing! I’ll see you in court!
More money, more life
Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.
Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.
“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.
But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.
We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
Holding the ‘health care and wellness’ gun
Cigarettes are not good for us. We know this.
It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.
Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.
And if those aren’t egregious business euphemisms, we don’t know what is.
Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?
So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.
Okay, we lied, it’s the second one.
Autopsy of the living dead
Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.
Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.
It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.
Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
When is MRI useful in the management of congenital melanocytic nevi?
When used for appropriate patients, results from a small multi-institutional study showed.
“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”
One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.
“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.
To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.
The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).
“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.
The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.
All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”
The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.
Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.
“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”
Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.
Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.
When used for appropriate patients, results from a small multi-institutional study showed.
“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”
One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.
“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.
To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.
The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).
“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.
The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.
All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”
The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.
Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.
“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”
Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.
Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.
When used for appropriate patients, results from a small multi-institutional study showed.
“The majority of congenital nevi are considered low risk for cutaneous and/or systemic complications,” Holly Neale said at the annual meeting of the Society for Pediatric Dermatology. “However, a subset of children born with higher-risk congenital nevi require close monitoring, as some features of congenital nevi have been associated with cutaneous melanoma, central nervous system melanoma, melanin in the brain or spine, and structural irregularities in the brain or spine. It’s important to understand which congenital nevi are considered higher risk in order to guide management and counseling decisions.”
One major management decision is to do a screening magnetic resonance image of the CNS to evaluate for neurologic involvement, said Ms. Neale, a fourth-year medical student at the University of Massachusetts, Worcester. Prior studies have shown that congenital nevi that are bigger than 20 cm, posterior axial location, and having more than one congenital nevus may predict CNS abnormalities, while recent guidelines from experts in the field suggest that any child with more than one congenital nevus at birth undergo screening MRI.
“However, guidelines are evolving, and more data is required to better understand the CNS abnormalities and patient outcomes for children with congenital nevi,” said Ms. Neale, who spent the past year as a pediatric dermatology research fellow at Massachusetts General Hospital, Boston.
To address this knowledge gap, she and colleagues at the University of Massachusetts, Massachusetts General Hospital, and Boston Children’s Hospital performed a retrospective chart review between Jan. 1, 2009, and Dec. 31, 2019, of individuals ages 18 and younger who had an MRI of the brain or spine with at least one dermatologist-diagnosed nevus as identified via key words in the medical record. Of the 909 patients screened, 46 met inclusion criteria, evenly split between males and females.
The most common location of the largest nevus was the trunk (in 41% of patients), followed by lesions that spanned multiple regions. More than one-third of patients had giant nevi (greater than 40 cm).
“The majority of images were considered nonconcerning, which includes normal, benign, or other findings such as trauma related, infectious, or orthopedic, which we did not classify as abnormal as it did not guide our study question,” Ms. Neale said. Specifically, 8% of spine images and 27% of brain images were considered “concerning,” defined as any finding that prompted further workup or monitoring, which includes findings concerning for melanin.
The most common brain finding was melanin (in eight children), and one child with brain melanin also had findings suggestive of melanin in the thoracic spine. The most common finding in spine MRIs was fatty filum (in four children), requiring intervention for tethering in only one individual. No cases of cutaneous melanoma developed during the study period, and only one patient with abnormal imaging had CNS melanoma, which was fatal.
All patients with findings suggestive of CNS melanin had more than four nevi present at birth, which is in line with current imaging screening guidelines. In addition, children with concerning imaging had higher rates of death, neurodevelopmental problems, seizures, and neurosurgery, compared with their counterparts with unremarkable imaging findings. Describing preliminary analyses, Ms. Neale said that a chi square analysis was performed to test statistical significance of these differences, “and neurosurgery was the only variable that children with concerning imaging were significantly more likely to experience, although sample size limits detection for the other variables.”
The authors concluded that MRI is a helpful tool when used in the appropriate clinical context for the management of congenital nevi. “As more children undergo imaging, we may discover more nonmelanin abnormalities,” she said.
Joseph M. Lam, MD, who was asked to comment on the study, said that the increased risk of CNS melanin in patients with larger lesions and in those with multiple lesions confirms previous reports.
“It is interesting to note that some patients with nonconcerning imaging results still had neurodevelopmental problems and seizures, albeit at a lower rate than those with concerning imaging results,” said Dr. Lam, a pediatric dermatologist at British Columbia Children’s Hospital, Vancouver. “The lack of a control group for comparison of rates of neurological sequelae, such as NDP, seizures and nonmelanin structural anomalies, limits the generalizability of the findings. However, this is a nice study that helps us understand better the CNS anomalies in CMN.”
Ms. Neale acknowledged certain limitations of the study, including the lack of a control group without CMN, the small number of patients, the potential for referral bias, and its retrospective design. Also, the proximity of the study period does not allow for chronic follow-up and detection of the development of melanoma or other problems in the future.
Ms. Neale and associates reported having no relevant financial disclosures. Dr. Lam disclosed that he has received speaker fees from Pierre Fabre.
FROM SPD 2021