User login
COVID infection provides immunity equal to vaccination: Study
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
FROM THE LANCET
Untreated COVID often involves relapse, clarifying antiviral rebound discussion
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
‘Infuriating’ prescription denial leaves patient without antiemetics
It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.
The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.
He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.
“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.
But when it came time to renew his ondansetron prescription, his insurance company denied it.
The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.
After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.
But it was already after 7:30 p.m. ET on Friday.
At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.
“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.
On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.
“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”
When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.
At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.
Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.
Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.
In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.
On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”
However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.
“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.
In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”
A version of this article first appeared on Medscape.com.
It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.
The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.
He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.
“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.
But when it came time to renew his ondansetron prescription, his insurance company denied it.
The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.
After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.
But it was already after 7:30 p.m. ET on Friday.
At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.
“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.
On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.
“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”
When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.
At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.
Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.
Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.
In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.
On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”
However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.
“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.
In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”
A version of this article first appeared on Medscape.com.
It was Friday, and oncologist Coral Olazagasti, MD, faced a ticking clock.
The patient – a man with HPV-related oropharyngeal cancer – was experiencing severe side effects from standard chemoradiation with weekly cisplatin. Intense nausea and grade 3 mucositis, in particular, left him struggling to swallow or take in any food or fluids.
He was on 8 mg of ondansetron (Zofran) every 8 hours, as needed, to keep the nausea at bay. The pills along with a feeding tube helped, but his symptoms were so intense, neither was quite enough.
“He still needed to be hospitalized twice for dehydration,” said Dr. Olazagasti, who specializes in head and neck medical cancer at Sylvester Comprehensive Cancer Center in Miami.
But when it came time to renew his ondansetron prescription, his insurance company denied it.
The reasoning: “The company had only approved 30 tablets a month and, for them, it was unjustifiable to approve anything above that amount,” Dr. Olazagasti explained.
After Dr. Olazagasti called the insurance company to resolve the issue, a company representative told her to fill out a prior authorization form.
But it was already after 7:30 p.m. ET on Friday.
At that point, finding the prior authorization documents, filling them out, and submitting them would take more time – and the paperwork couldn’t be filed until Monday.
“My patient was at home with zero tablets left and horrible symptoms. He couldn’t keep anything down,” Dr. Olazagasti said.
On Monday, the oncology team sent the prior authorization request, and her patient received his medication a few days later.
“My patient had to wait about 5 days to get the nausea meds he needed,” she said. In the meantime, he was in pain. “Having a refill of this simple supportive care medication rejected was infuriating.”
When Dr. Olazagasti vented her frustrations on Twitter, several people chimed in, suggesting purchasing the drug at a discount through GoodRx or Cost Plus instead of going through the insurance company.
At Cost Plus, for instance, 30 8-mg pills would cost $6.30, but ordering from the online pharmacy would mean waiting several days for delivery.
Discounts through GoodRx may provide a potentially faster solution in a pinch, but the pharmacy matters. In Miami, 30 8-mg pills would cost $19.99 at Costco with a GoodRx coupon, but $233.56 at CVS and $253.60 at Walgreens.
Although potentially useful, these options may not be the obvious choice for oncologists and patients, especially when a drug has already been approved and covered by the insurer. In this case, the denial was also a surprise, which left Dr. Olazagasti and her patient scrambling right before the weekend.
In addition, companies providing discounted generic drugs may only have a limited number of oncology-related medications. Cost Plus, for instance, now sells more than 1,000 generic prescription drugs at a fraction of what insurance companies charge, but only about 7 are cancer drugs.
On a broader level, Dr. Olazagasti noted, “insurance companies have a responsibility to cover these drugs. If we all get so fed up that we start relying on alternate routes to get patients their treatments, then insurance companies are let off the hook.”
However, using an alternative option like GoodRx or CostPlus could mean bypassing insurance company obstacles in certain cases.
“The hurdles someone may have to go through to get a generic drug approved are very frustrating,” said Stacie B. Dusetzina, PhD, professor of health policy and a professor of cancer research at Vanderbilt University in Nashville, Tenn.
In a weekend emergency situation, if the drug is discounted through GoodRx, “it can be a good backup strategy to send the prescription to the pharmacy” and more generally “worth it for patients to check if they can get a better deal on generic drugs through these companies.”
A version of this article first appeared on Medscape.com.
COVID-19 shot appears to reduce diabetes risk, even after Omicron
new data suggest.
The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.
Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.
However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.
“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.
“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.
Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”
The findings were published online in JAMA Network Open.
Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.
Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.
The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).
Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).
The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).
However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.
There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.
Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”
He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”
This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.
A version of this article originally appeared on Medscape.com.
new data suggest.
The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.
Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.
However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.
“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.
“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.
Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”
The findings were published online in JAMA Network Open.
Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.
Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.
The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).
Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).
The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).
However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.
There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.
Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”
He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”
This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.
A version of this article originally appeared on Medscape.com.
new data suggest.
The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.
Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.
However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.
“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.
“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.
Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”
The findings were published online in JAMA Network Open.
Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.
Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.
The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).
Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).
The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).
However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.
There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.
Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”
He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”
This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.
A version of this article originally appeared on Medscape.com.
FROM JAMA NETWORK OPEN
New challenge for docs: End of COVID federal public health emergency
The Biden administration intends to end by May 11 certain COVID-19 emergency measures used to aid in the response to the pandemic, while many others will remain in place.
A separate declaration covers the Food and Drug Administration’s emergency use authorizations (EUAs) for COVID medicines and tests. That would not be affected by the May 11 deadline, the FDA said. In addition, Congress and state lawmakers have extended some COVID response measures.
The result is a patchwork of emergency COVID-19 measures with different end dates.
The American Medical Association and the American Academy of Family Physicians (AAFP) are assessing how best to advise their members about the end of the public health emergency.
Several waivers regarding copays and coverage and policies regarding controlled substances will expire, Claire Ernst, director of government affairs at the Medical Group Management Association, told this news organization.
The impact of the unwinding “will vary based on some factors, such as what state the practice resides in,” Ms. Ernst said. “Fortunately, Congress provided some predictability for practices by extending many of the telehealth waivers through the end of 2024.”
The AAFP told this news organization that it has joined several other groups in calling for the release of proposed Drug Enforcement Administration (DEA) regulations meant to permanently allow prescriptions of buprenorphine treatment for opioid use disorder via telehealth. The AAFP and other groups want to review these proposals and, if needed, urge the DEA to modify or finalize before there are any disruptions in access to medications for opioid use disorder.
Patients’ questions
Clinicians can expect to field patients’ questions about their insurance coverage and what they need to pay, said Nancy Foster, vice president for quality and patient safety policy at the American Hospital Association (AHA).
“Your doctor’s office, that clinic you typically get care at, that is the face of medicine to you,” Ms. Foster told this news organization. “Many doctors and their staff will be asked, ‘What’s happening with Medicaid?’ ‘What about my Medicare coverage?’ ‘Can I still access care in the same way that I did before?’ ”
Physicians will need to be ready to answers those question, or point patients to where they can get answers, Ms. Foster said.
For example, Medicaid will no longer cover postpartum care for some enrollees after giving birth, said Taylor Platt, health policy manager for the American College of Obstetricians and Gynecologists.
The federal response to the pandemic created “a de facto postpartum coverage extension for Medicaid enrollees,” which will be lost in some states, Ms. Platt told this news organization. However, 28 states and the District of Columbia have taken separate measures to extend postpartum coverage to 1 year.
“This coverage has been critical for postpartum individuals to address health needs like substance use and mental health treatment and chronic conditions,” Ms. Platt said.
States significantly changed Medicaid policy to expand access to care during the pandemic.
All 50 states and the District of Columbia, for example, expanded coverage or access to telehealth services in Medicaid during the pandemic, according to a Jan. 31 report from the Kaiser Family Foundation (KFF). These expansions expire under various deadlines, although most states have made or are planning to make some Medicaid telehealth flexibilities permanent, KFF said.
The KFF report notes that all states and the District of Columbia temporarily waived some aspects of state licensure requirements, so that clinicians with equivalent licenses in other states could practice via telehealth.
In some states, these waivers are still active and are tied to the end of the federal emergency declaration. In others, they expired, with some states allowing for long-term or permanent interstate telemedicine, KFF said. (The Federation of State Medical Boards has a detailed summary of these modifications.)
The end of free COVID vaccines, testing for some patients
The AAFP has also raised concerns about continued access to COVID-19 vaccines, particularly for uninsured adults. Ashish Jha, MD, MPH, the White House COVID-19 Response Coordinator, said in a tweet that this transition, however, wouldn’t happen until a few months after the public health emergency ends.
After those few months, there will be a transition from U.S. government–distributed vaccines and treatments to ones purchased through the regular health care system, the “way we do for every other vaccine and treatment,” Dr. Jha added.
But that raises the same kind of difficult questions that permeate U.S. health care, with a potential to keep COVID active, said Patricia Jackson, RN, president of the Association for Professionals in Infection Control and Epidemiology (APIC).
People who don’t have insurance may lose access to COVID testing and vaccines.
“Will that lead to increases in transmission? Who knows,” Ms. Jackson told this news organization. “We will have to see. There are some health equity issues that potentially arise.”
Future FDA actions
Biden’s May 11 deadline applies to emergency provisions made under a Section 319 declaration, which allow the Department of Health and Human Services to respond to crises.
But a separate flexibility, known as a Section 564 declaration, covers the FDA’s EUAs, which can remain in effect even as the other declarations end.
The best-known EUAs for the pandemic were used to bring COVID vaccines and treatments to market. Many of these have since been converted to normal approvals as companies presented more evidence to support the initial emergency approvals. In other cases, EUAs have been withdrawn owing to disappointing research results, changing virus strains, and evolving medical treatments.
The FDA also used many EUAs to cover new uses of ventilators and other hospital equipment and expand these supplies in response to the pandemic, said Mark Howell, AHA’s director of policy and patient safety.
The FDA should examine the EUAs issued during the pandemic to see what greater flexibilities might be used to deal with future serious shortages of critical supplies. International incidents such as the war in Ukraine show how fragile the supply chain can be. The FDA should consider its recent experience with EUAs to address this, Mr. Howell said.
“What do we do coming out of the pandemic? And how do we think about being more proactive in this space to ensure that our supply doesn’t bottleneck, that we continue to make sure that providers have access to supply that’s not only safe and effective, but that they can use?” Mr. Howell told this news organization.
Such planning might also help prepare the country for the next pandemic, which is a near certainty, APIC’s Ms. Jackson said. The nation needs a nimbler response to the next major outbreak of an infectious disease, she said.
“There is going to be a next time,” Ms. Jackson said. “We are going to have another pandemic.”
A version of this article first appeared on Medscape.com.
The Biden administration intends to end by May 11 certain COVID-19 emergency measures used to aid in the response to the pandemic, while many others will remain in place.
A separate declaration covers the Food and Drug Administration’s emergency use authorizations (EUAs) for COVID medicines and tests. That would not be affected by the May 11 deadline, the FDA said. In addition, Congress and state lawmakers have extended some COVID response measures.
The result is a patchwork of emergency COVID-19 measures with different end dates.
The American Medical Association and the American Academy of Family Physicians (AAFP) are assessing how best to advise their members about the end of the public health emergency.
Several waivers regarding copays and coverage and policies regarding controlled substances will expire, Claire Ernst, director of government affairs at the Medical Group Management Association, told this news organization.
The impact of the unwinding “will vary based on some factors, such as what state the practice resides in,” Ms. Ernst said. “Fortunately, Congress provided some predictability for practices by extending many of the telehealth waivers through the end of 2024.”
The AAFP told this news organization that it has joined several other groups in calling for the release of proposed Drug Enforcement Administration (DEA) regulations meant to permanently allow prescriptions of buprenorphine treatment for opioid use disorder via telehealth. The AAFP and other groups want to review these proposals and, if needed, urge the DEA to modify or finalize before there are any disruptions in access to medications for opioid use disorder.
Patients’ questions
Clinicians can expect to field patients’ questions about their insurance coverage and what they need to pay, said Nancy Foster, vice president for quality and patient safety policy at the American Hospital Association (AHA).
“Your doctor’s office, that clinic you typically get care at, that is the face of medicine to you,” Ms. Foster told this news organization. “Many doctors and their staff will be asked, ‘What’s happening with Medicaid?’ ‘What about my Medicare coverage?’ ‘Can I still access care in the same way that I did before?’ ”
Physicians will need to be ready to answers those question, or point patients to where they can get answers, Ms. Foster said.
For example, Medicaid will no longer cover postpartum care for some enrollees after giving birth, said Taylor Platt, health policy manager for the American College of Obstetricians and Gynecologists.
The federal response to the pandemic created “a de facto postpartum coverage extension for Medicaid enrollees,” which will be lost in some states, Ms. Platt told this news organization. However, 28 states and the District of Columbia have taken separate measures to extend postpartum coverage to 1 year.
“This coverage has been critical for postpartum individuals to address health needs like substance use and mental health treatment and chronic conditions,” Ms. Platt said.
States significantly changed Medicaid policy to expand access to care during the pandemic.
All 50 states and the District of Columbia, for example, expanded coverage or access to telehealth services in Medicaid during the pandemic, according to a Jan. 31 report from the Kaiser Family Foundation (KFF). These expansions expire under various deadlines, although most states have made or are planning to make some Medicaid telehealth flexibilities permanent, KFF said.
The KFF report notes that all states and the District of Columbia temporarily waived some aspects of state licensure requirements, so that clinicians with equivalent licenses in other states could practice via telehealth.
In some states, these waivers are still active and are tied to the end of the federal emergency declaration. In others, they expired, with some states allowing for long-term or permanent interstate telemedicine, KFF said. (The Federation of State Medical Boards has a detailed summary of these modifications.)
The end of free COVID vaccines, testing for some patients
The AAFP has also raised concerns about continued access to COVID-19 vaccines, particularly for uninsured adults. Ashish Jha, MD, MPH, the White House COVID-19 Response Coordinator, said in a tweet that this transition, however, wouldn’t happen until a few months after the public health emergency ends.
After those few months, there will be a transition from U.S. government–distributed vaccines and treatments to ones purchased through the regular health care system, the “way we do for every other vaccine and treatment,” Dr. Jha added.
But that raises the same kind of difficult questions that permeate U.S. health care, with a potential to keep COVID active, said Patricia Jackson, RN, president of the Association for Professionals in Infection Control and Epidemiology (APIC).
People who don’t have insurance may lose access to COVID testing and vaccines.
“Will that lead to increases in transmission? Who knows,” Ms. Jackson told this news organization. “We will have to see. There are some health equity issues that potentially arise.”
Future FDA actions
Biden’s May 11 deadline applies to emergency provisions made under a Section 319 declaration, which allow the Department of Health and Human Services to respond to crises.
But a separate flexibility, known as a Section 564 declaration, covers the FDA’s EUAs, which can remain in effect even as the other declarations end.
The best-known EUAs for the pandemic were used to bring COVID vaccines and treatments to market. Many of these have since been converted to normal approvals as companies presented more evidence to support the initial emergency approvals. In other cases, EUAs have been withdrawn owing to disappointing research results, changing virus strains, and evolving medical treatments.
The FDA also used many EUAs to cover new uses of ventilators and other hospital equipment and expand these supplies in response to the pandemic, said Mark Howell, AHA’s director of policy and patient safety.
The FDA should examine the EUAs issued during the pandemic to see what greater flexibilities might be used to deal with future serious shortages of critical supplies. International incidents such as the war in Ukraine show how fragile the supply chain can be. The FDA should consider its recent experience with EUAs to address this, Mr. Howell said.
“What do we do coming out of the pandemic? And how do we think about being more proactive in this space to ensure that our supply doesn’t bottleneck, that we continue to make sure that providers have access to supply that’s not only safe and effective, but that they can use?” Mr. Howell told this news organization.
Such planning might also help prepare the country for the next pandemic, which is a near certainty, APIC’s Ms. Jackson said. The nation needs a nimbler response to the next major outbreak of an infectious disease, she said.
“There is going to be a next time,” Ms. Jackson said. “We are going to have another pandemic.”
A version of this article first appeared on Medscape.com.
The Biden administration intends to end by May 11 certain COVID-19 emergency measures used to aid in the response to the pandemic, while many others will remain in place.
A separate declaration covers the Food and Drug Administration’s emergency use authorizations (EUAs) for COVID medicines and tests. That would not be affected by the May 11 deadline, the FDA said. In addition, Congress and state lawmakers have extended some COVID response measures.
The result is a patchwork of emergency COVID-19 measures with different end dates.
The American Medical Association and the American Academy of Family Physicians (AAFP) are assessing how best to advise their members about the end of the public health emergency.
Several waivers regarding copays and coverage and policies regarding controlled substances will expire, Claire Ernst, director of government affairs at the Medical Group Management Association, told this news organization.
The impact of the unwinding “will vary based on some factors, such as what state the practice resides in,” Ms. Ernst said. “Fortunately, Congress provided some predictability for practices by extending many of the telehealth waivers through the end of 2024.”
The AAFP told this news organization that it has joined several other groups in calling for the release of proposed Drug Enforcement Administration (DEA) regulations meant to permanently allow prescriptions of buprenorphine treatment for opioid use disorder via telehealth. The AAFP and other groups want to review these proposals and, if needed, urge the DEA to modify or finalize before there are any disruptions in access to medications for opioid use disorder.
Patients’ questions
Clinicians can expect to field patients’ questions about their insurance coverage and what they need to pay, said Nancy Foster, vice president for quality and patient safety policy at the American Hospital Association (AHA).
“Your doctor’s office, that clinic you typically get care at, that is the face of medicine to you,” Ms. Foster told this news organization. “Many doctors and their staff will be asked, ‘What’s happening with Medicaid?’ ‘What about my Medicare coverage?’ ‘Can I still access care in the same way that I did before?’ ”
Physicians will need to be ready to answers those question, or point patients to where they can get answers, Ms. Foster said.
For example, Medicaid will no longer cover postpartum care for some enrollees after giving birth, said Taylor Platt, health policy manager for the American College of Obstetricians and Gynecologists.
The federal response to the pandemic created “a de facto postpartum coverage extension for Medicaid enrollees,” which will be lost in some states, Ms. Platt told this news organization. However, 28 states and the District of Columbia have taken separate measures to extend postpartum coverage to 1 year.
“This coverage has been critical for postpartum individuals to address health needs like substance use and mental health treatment and chronic conditions,” Ms. Platt said.
States significantly changed Medicaid policy to expand access to care during the pandemic.
All 50 states and the District of Columbia, for example, expanded coverage or access to telehealth services in Medicaid during the pandemic, according to a Jan. 31 report from the Kaiser Family Foundation (KFF). These expansions expire under various deadlines, although most states have made or are planning to make some Medicaid telehealth flexibilities permanent, KFF said.
The KFF report notes that all states and the District of Columbia temporarily waived some aspects of state licensure requirements, so that clinicians with equivalent licenses in other states could practice via telehealth.
In some states, these waivers are still active and are tied to the end of the federal emergency declaration. In others, they expired, with some states allowing for long-term or permanent interstate telemedicine, KFF said. (The Federation of State Medical Boards has a detailed summary of these modifications.)
The end of free COVID vaccines, testing for some patients
The AAFP has also raised concerns about continued access to COVID-19 vaccines, particularly for uninsured adults. Ashish Jha, MD, MPH, the White House COVID-19 Response Coordinator, said in a tweet that this transition, however, wouldn’t happen until a few months after the public health emergency ends.
After those few months, there will be a transition from U.S. government–distributed vaccines and treatments to ones purchased through the regular health care system, the “way we do for every other vaccine and treatment,” Dr. Jha added.
But that raises the same kind of difficult questions that permeate U.S. health care, with a potential to keep COVID active, said Patricia Jackson, RN, president of the Association for Professionals in Infection Control and Epidemiology (APIC).
People who don’t have insurance may lose access to COVID testing and vaccines.
“Will that lead to increases in transmission? Who knows,” Ms. Jackson told this news organization. “We will have to see. There are some health equity issues that potentially arise.”
Future FDA actions
Biden’s May 11 deadline applies to emergency provisions made under a Section 319 declaration, which allow the Department of Health and Human Services to respond to crises.
But a separate flexibility, known as a Section 564 declaration, covers the FDA’s EUAs, which can remain in effect even as the other declarations end.
The best-known EUAs for the pandemic were used to bring COVID vaccines and treatments to market. Many of these have since been converted to normal approvals as companies presented more evidence to support the initial emergency approvals. In other cases, EUAs have been withdrawn owing to disappointing research results, changing virus strains, and evolving medical treatments.
The FDA also used many EUAs to cover new uses of ventilators and other hospital equipment and expand these supplies in response to the pandemic, said Mark Howell, AHA’s director of policy and patient safety.
The FDA should examine the EUAs issued during the pandemic to see what greater flexibilities might be used to deal with future serious shortages of critical supplies. International incidents such as the war in Ukraine show how fragile the supply chain can be. The FDA should consider its recent experience with EUAs to address this, Mr. Howell said.
“What do we do coming out of the pandemic? And how do we think about being more proactive in this space to ensure that our supply doesn’t bottleneck, that we continue to make sure that providers have access to supply that’s not only safe and effective, but that they can use?” Mr. Howell told this news organization.
Such planning might also help prepare the country for the next pandemic, which is a near certainty, APIC’s Ms. Jackson said. The nation needs a nimbler response to the next major outbreak of an infectious disease, she said.
“There is going to be a next time,” Ms. Jackson said. “We are going to have another pandemic.”
A version of this article first appeared on Medscape.com.
USPSTF recommends against routine herpes screening for asymptomatic teens and adults
Asymptomatic adults, teens, and pregnant women with no known history or symptoms of herpes infection need not undergo routine screening, according to the latest recommendation from the U.S. Preventive Services Task Force.
The 2023 recommendation reaffirms the conclusion from 2016, wrote Carol M. Mangione, MD, of the University of California, Los Angeles, and members of the task force.
“Currently, routine serologic screening for genital herpes is limited by the low predictive value of the widely available serologic screening tests and the expected high rate of false-positive results likely to occur with routine screening of asymptomatic persons in the U.S.,” the authors said.
In the recommendation, published in JAMA, the authors affirmed with moderate certainty and a grade D recommendation that the risks of routine screening for herpes simplex virus (HSV) in asymptomatic individuals outweigh the benefits.
The task force found no new evidence on the accuracy of serologic screening tests, the benefits of early detection and treatment, or on the harms of screening and treatment since the 2016 review of 17 studies in 19 publications, with data from more than 9,000 individuals.
Studies of the accuracy of serologic screening for herpes simplex virus-2 in the 2016 report mainly reflect populations with higher HSV-2 prevalence and are of limited applicability to the U.S. primary care population, the authors wrote. Evidence from the 2016 review also showed limited and inconsistent support for the early identification and treatment of HSV-2 in asymptomatic individuals, including those who were pregnant.
No new evidence has emerged since 2016 regarding harms of screening or treating genital herpes in asymptomatic individuals, the authors noted. “Based on previous evidence, the USPSTF estimated that using the widely available serologic tests for HSV-2, nearly 1 of every 2 diagnoses in the general U.S. primary care population could be false,” they said. The task force also concluded that the low accuracy of the current tests could prompt unnecessary treatment for individuals with false-positive diagnoses, as well as social and emotional harm for these individuals.
During a period of public comment from Aug. 16, 2022, to Sept. 12, 2022, individuals expressed concerns that the recommendation against routine screening showed a disinclination to take herpes seriously, and concerns that asymptomatic individuals could transmit the infection to sexual partners, the authors said. However, the estimated seroprevalence of HSV-1 and HSV-2 has declined in recent decades, and other comments supported the USPSTF’s analysis of the evidence and noted their consistency with current clinical practice.
The task force noted that research gaps remain and recognized the need to improve screening and treatment of genital herpes to prevent symptomatic episodes and transmission. Specifically, the USPSTF recommendation calls for more research to assess the accuracy of screening tests, to enroll more study participants from populations disproportionately affected by HSV, to examine the effect of behavioral counseling, and to clarify associations between HSV and pregnancy outcomes. In addition, the task force called for research to create an effective vaccine to prevent genital HSV infection and to develop a cure.
Targeted screening makes sense for now
“Given the frequency and severity of the range of diseases seen with HSV and the large proportion of persons who are asymptomatic, identifying carriers through type-specific serologic screening has long been considered a plausible strategy,” Mark D. Pearlman, MD, of the University of Michigan, Ann Arbor, wrote in an accompanying editorial.
However, accuracy of the currently available serology screening tests is low, and the adverse social and psychological effects and the impact on relationships for many asymptomatic individuals who test positive and may be incorrectly identified as infected remains a concern, said Dr. Pearlman.
Although some may be disagree about the value of routine serotesting for HSV-2 in asymptomatic individuals, other strategies can reduce the spread of infection and help those infected, he said.
Many experts continue to recommend targeted serotesting to high-risk populations, such as pregnant women whose nonpregnant partner is known to have genital or oral herpes and whose own infection status or serostatus is uncertain, said Dr. Pearlman. Other targeted strategies include screening individuals with recurrent or atypical genital symptoms and negative polymerase chain reaction assay or culture results, a clinical herpes diagnosis without laboratory confirmation, or those at increased risk because of a high number of sexual partners or a history of HIV infection, he said.
“Of note, the current CDC STI guidelines and ACOG both concur with the USPSTF that routine screening in the general population or routine screening during pregnancy are not recommended,” Dr. Pearlman said. Meanwhile, research efforts continue to help reduce the impact of HSV disease and development of a more effective testing methodology “might tip the balance in favor of routine screening” in the future, he emphasized.
The recommendations were supported by the Agency for Healthcare Research and Quality. The members of the task force received reimbursement for travel and an honorarium but had no other relevant financial conflicts to disclose. Dr. Pearlman had no financial conflicts to disclose.
Asymptomatic adults, teens, and pregnant women with no known history or symptoms of herpes infection need not undergo routine screening, according to the latest recommendation from the U.S. Preventive Services Task Force.
The 2023 recommendation reaffirms the conclusion from 2016, wrote Carol M. Mangione, MD, of the University of California, Los Angeles, and members of the task force.
“Currently, routine serologic screening for genital herpes is limited by the low predictive value of the widely available serologic screening tests and the expected high rate of false-positive results likely to occur with routine screening of asymptomatic persons in the U.S.,” the authors said.
In the recommendation, published in JAMA, the authors affirmed with moderate certainty and a grade D recommendation that the risks of routine screening for herpes simplex virus (HSV) in asymptomatic individuals outweigh the benefits.
The task force found no new evidence on the accuracy of serologic screening tests, the benefits of early detection and treatment, or on the harms of screening and treatment since the 2016 review of 17 studies in 19 publications, with data from more than 9,000 individuals.
Studies of the accuracy of serologic screening for herpes simplex virus-2 in the 2016 report mainly reflect populations with higher HSV-2 prevalence and are of limited applicability to the U.S. primary care population, the authors wrote. Evidence from the 2016 review also showed limited and inconsistent support for the early identification and treatment of HSV-2 in asymptomatic individuals, including those who were pregnant.
No new evidence has emerged since 2016 regarding harms of screening or treating genital herpes in asymptomatic individuals, the authors noted. “Based on previous evidence, the USPSTF estimated that using the widely available serologic tests for HSV-2, nearly 1 of every 2 diagnoses in the general U.S. primary care population could be false,” they said. The task force also concluded that the low accuracy of the current tests could prompt unnecessary treatment for individuals with false-positive diagnoses, as well as social and emotional harm for these individuals.
During a period of public comment from Aug. 16, 2022, to Sept. 12, 2022, individuals expressed concerns that the recommendation against routine screening showed a disinclination to take herpes seriously, and concerns that asymptomatic individuals could transmit the infection to sexual partners, the authors said. However, the estimated seroprevalence of HSV-1 and HSV-2 has declined in recent decades, and other comments supported the USPSTF’s analysis of the evidence and noted their consistency with current clinical practice.
The task force noted that research gaps remain and recognized the need to improve screening and treatment of genital herpes to prevent symptomatic episodes and transmission. Specifically, the USPSTF recommendation calls for more research to assess the accuracy of screening tests, to enroll more study participants from populations disproportionately affected by HSV, to examine the effect of behavioral counseling, and to clarify associations between HSV and pregnancy outcomes. In addition, the task force called for research to create an effective vaccine to prevent genital HSV infection and to develop a cure.
Targeted screening makes sense for now
“Given the frequency and severity of the range of diseases seen with HSV and the large proportion of persons who are asymptomatic, identifying carriers through type-specific serologic screening has long been considered a plausible strategy,” Mark D. Pearlman, MD, of the University of Michigan, Ann Arbor, wrote in an accompanying editorial.
However, accuracy of the currently available serology screening tests is low, and the adverse social and psychological effects and the impact on relationships for many asymptomatic individuals who test positive and may be incorrectly identified as infected remains a concern, said Dr. Pearlman.
Although some may be disagree about the value of routine serotesting for HSV-2 in asymptomatic individuals, other strategies can reduce the spread of infection and help those infected, he said.
Many experts continue to recommend targeted serotesting to high-risk populations, such as pregnant women whose nonpregnant partner is known to have genital or oral herpes and whose own infection status or serostatus is uncertain, said Dr. Pearlman. Other targeted strategies include screening individuals with recurrent or atypical genital symptoms and negative polymerase chain reaction assay or culture results, a clinical herpes diagnosis without laboratory confirmation, or those at increased risk because of a high number of sexual partners or a history of HIV infection, he said.
“Of note, the current CDC STI guidelines and ACOG both concur with the USPSTF that routine screening in the general population or routine screening during pregnancy are not recommended,” Dr. Pearlman said. Meanwhile, research efforts continue to help reduce the impact of HSV disease and development of a more effective testing methodology “might tip the balance in favor of routine screening” in the future, he emphasized.
The recommendations were supported by the Agency for Healthcare Research and Quality. The members of the task force received reimbursement for travel and an honorarium but had no other relevant financial conflicts to disclose. Dr. Pearlman had no financial conflicts to disclose.
Asymptomatic adults, teens, and pregnant women with no known history or symptoms of herpes infection need not undergo routine screening, according to the latest recommendation from the U.S. Preventive Services Task Force.
The 2023 recommendation reaffirms the conclusion from 2016, wrote Carol M. Mangione, MD, of the University of California, Los Angeles, and members of the task force.
“Currently, routine serologic screening for genital herpes is limited by the low predictive value of the widely available serologic screening tests and the expected high rate of false-positive results likely to occur with routine screening of asymptomatic persons in the U.S.,” the authors said.
In the recommendation, published in JAMA, the authors affirmed with moderate certainty and a grade D recommendation that the risks of routine screening for herpes simplex virus (HSV) in asymptomatic individuals outweigh the benefits.
The task force found no new evidence on the accuracy of serologic screening tests, the benefits of early detection and treatment, or on the harms of screening and treatment since the 2016 review of 17 studies in 19 publications, with data from more than 9,000 individuals.
Studies of the accuracy of serologic screening for herpes simplex virus-2 in the 2016 report mainly reflect populations with higher HSV-2 prevalence and are of limited applicability to the U.S. primary care population, the authors wrote. Evidence from the 2016 review also showed limited and inconsistent support for the early identification and treatment of HSV-2 in asymptomatic individuals, including those who were pregnant.
No new evidence has emerged since 2016 regarding harms of screening or treating genital herpes in asymptomatic individuals, the authors noted. “Based on previous evidence, the USPSTF estimated that using the widely available serologic tests for HSV-2, nearly 1 of every 2 diagnoses in the general U.S. primary care population could be false,” they said. The task force also concluded that the low accuracy of the current tests could prompt unnecessary treatment for individuals with false-positive diagnoses, as well as social and emotional harm for these individuals.
During a period of public comment from Aug. 16, 2022, to Sept. 12, 2022, individuals expressed concerns that the recommendation against routine screening showed a disinclination to take herpes seriously, and concerns that asymptomatic individuals could transmit the infection to sexual partners, the authors said. However, the estimated seroprevalence of HSV-1 and HSV-2 has declined in recent decades, and other comments supported the USPSTF’s analysis of the evidence and noted their consistency with current clinical practice.
The task force noted that research gaps remain and recognized the need to improve screening and treatment of genital herpes to prevent symptomatic episodes and transmission. Specifically, the USPSTF recommendation calls for more research to assess the accuracy of screening tests, to enroll more study participants from populations disproportionately affected by HSV, to examine the effect of behavioral counseling, and to clarify associations between HSV and pregnancy outcomes. In addition, the task force called for research to create an effective vaccine to prevent genital HSV infection and to develop a cure.
Targeted screening makes sense for now
“Given the frequency and severity of the range of diseases seen with HSV and the large proportion of persons who are asymptomatic, identifying carriers through type-specific serologic screening has long been considered a plausible strategy,” Mark D. Pearlman, MD, of the University of Michigan, Ann Arbor, wrote in an accompanying editorial.
However, accuracy of the currently available serology screening tests is low, and the adverse social and psychological effects and the impact on relationships for many asymptomatic individuals who test positive and may be incorrectly identified as infected remains a concern, said Dr. Pearlman.
Although some may be disagree about the value of routine serotesting for HSV-2 in asymptomatic individuals, other strategies can reduce the spread of infection and help those infected, he said.
Many experts continue to recommend targeted serotesting to high-risk populations, such as pregnant women whose nonpregnant partner is known to have genital or oral herpes and whose own infection status or serostatus is uncertain, said Dr. Pearlman. Other targeted strategies include screening individuals with recurrent or atypical genital symptoms and negative polymerase chain reaction assay or culture results, a clinical herpes diagnosis without laboratory confirmation, or those at increased risk because of a high number of sexual partners or a history of HIV infection, he said.
“Of note, the current CDC STI guidelines and ACOG both concur with the USPSTF that routine screening in the general population or routine screening during pregnancy are not recommended,” Dr. Pearlman said. Meanwhile, research efforts continue to help reduce the impact of HSV disease and development of a more effective testing methodology “might tip the balance in favor of routine screening” in the future, he emphasized.
The recommendations were supported by the Agency for Healthcare Research and Quality. The members of the task force received reimbursement for travel and an honorarium but had no other relevant financial conflicts to disclose. Dr. Pearlman had no financial conflicts to disclose.
FROM JAMA
NICU use up, birth weights down in babies of mothers with HCV
Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.
Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”
For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).
The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.
An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.
There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).
No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.
“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.
She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”
Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”
As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”
At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”
The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).
Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.
Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”
For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).
The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.
An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.
There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).
No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.
“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.
She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”
Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”
As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”
At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”
The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).
Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.
Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”
For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).
The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.
An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.
There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).
No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.
“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.
She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”
Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”
As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”
At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”
The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).
FROM THE PREGNANCY MEETING
Risk of infections low among kids receiving systemic meds for psoriasis, study finds
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
.
Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.
“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”
Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.
Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.
Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”
She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”
Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.
FROM JAMA DERMATOLOGY
Must-read acute care medicine articles from 2022
When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.
Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic.
Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.
As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
Myocardial dysfunction after cardiac arrest: Tips and pitfalls
The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.
Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).
They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release
I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.
Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.
In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.
The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
Top myths of diagnosis and management of infectious diseases in hospital medicine
Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!
This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:
- “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
- “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
- “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
- “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
- “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.
The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
Guidelines for low-risk, recurrent abdominal pain in the emergency department
The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.
Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?
Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:
- Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.
Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
In summary
There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.
Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.
Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic.
Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.
As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
Myocardial dysfunction after cardiac arrest: Tips and pitfalls
The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.
Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).
They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release
I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.
Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.
In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.
The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
Top myths of diagnosis and management of infectious diseases in hospital medicine
Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!
This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:
- “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
- “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
- “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
- “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
- “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.
The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
Guidelines for low-risk, recurrent abdominal pain in the emergency department
The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.
Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?
Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:
- Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.
Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
In summary
There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.
Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.
Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic.
Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.
As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
Myocardial dysfunction after cardiac arrest: Tips and pitfalls
The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.
Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).
They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release
I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.
Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.
In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.
The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
Top myths of diagnosis and management of infectious diseases in hospital medicine
Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!
This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:
- “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
- “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
- “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
- “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
- “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.
The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
Guidelines for low-risk, recurrent abdominal pain in the emergency department
The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.
Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?
Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:
- Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
- Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.
Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
In summary
There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.
Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Scientists create ‘vagina on a chip’: What to know
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
FROM MICROBIOME