Infectious Diseases

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

For many people, being told that they are HIV positive is no longer a death sentence. But for Robert Suttle, a Black gay man and social justice educator, it is a life sentence.

Unexpectedly caught up in the HIV criminalization web at the age of 30, Mr. Suttle spent 6 months in a Louisiana state prison for a consensual sexual relationship with an adult partner. The crime? Not disclosing his HIV-positive status, a charge that Mr. Suttle says is untrue.

“I did disclose my status to my partner; however, I can’t really answer how they might have received it,” he said.

Today, at the age of 42, Mr. Suttle still carries the indelible stain of a conviction and of being a registered sex offender. “After their diagnosis, criminal charge, and/or conviction, many people think they’re done – either ‘I’ve gotten out of prison’ or ‘I’m still on probation’ – whatever the case may be,” he explained. “But we’re still living out these collateral consequences, be it with housing, moving to another state, or finding a job.”

The same is true for HIV-positive people who are charged and tried but manage to dodge prison for one reason or another. Monique Howell, a straight, 40-year-old former army soldier and single mother of five children, said that she was afraid to disclose her HIV status to a sexual partner but did advise him to wear a condom.* She points to her DD14 discharge papers (i.e., forms that verify that someone served in the military) that were issued when her military duty was rescinded following the dismissal of her court case.

“I was going to reenlist, but I got in trouble,” she said. She explained that although a DD14 separation helps to ensure that she can receive benefits and care, the papers were issued with a caveat stating “serious offense,” an indelible stain that, like Mr. Suttle’s, will follow her for the rest of her life.
 

Laws criminalize myths and misconceptions

HIV criminalization laws subject persons whose behaviors may expose others to HIV to felony or misdemeanor charges. Depending on the state, they can carry prison terms ranging from less than 10 years to life, according to the Centers for Disease Control and Prevention.

Originally enacted at the height of the AIDS epidemic in 1986, when fear was rampant and hundreds were dying, the laws were intended to reduce HIV transmission. But they’ve had unintended consequences: Amplifying stigmatization and discrimination and perpetuating HIV myths and misconceptions, including how HIV is transmitted.

Decades of scientific advances challenge the most basic reasoning behind laws (for example, that transmission is possible via biting or spitting or through a single sexual act, which studies have shown poses a risk as low as 0%-1.4%). In addition, few laws reflect one of the most important HIV research findings of the past decade: undetectable equals untransmittable, meaning that the virus cannot be sexually transmitted by people who are taking antiretroviral therapy and whose viral loads are undetectable.

In most of these cases, individuals who are positive for HIV are charged and punished for unintentional exposure, not deliberate intent to harm. Moreover, for the charge to stick, sexual partners don’t need to have acquired the virus or prove the transmission source if they do become HIV positive.

Ms. Howell noted that it was the Army that brought the charges against her, not her sexual partner at that time (who, incidentally, tested negative). He even testified on her behalf at the trial. “I’ll never forget it,” she said. “He said, ‘I don’t want anything to happen to Monique; even if you put her behind bars, she’s still HIV-positive and she’s still got those children. She told me to get a condom, and I chose not to.’ ”
 

Criminal vs. clinical fallout

In 2018, 20 scientists across the world issued a consensus statement underscoring the fact that HIV criminalization laws are based on fallacies and faulty science. The statement (which remains one of the most accessed in the Journal of the International AIDS Society) also points out that 33 countries (including the United States) use general criminal statutes such as attempted murder or reckless endangerment to lengthen sentences when people with HIV commit crimes.

When the laws were created, “many were the equivalent [to general criminal laws], because HIV was seen as a death sentence,” explained Chris Beyrer MD, MPH, professor of public health and human rights at Johns Hopkins Bloomberg School of Public Health, Baltimore. “So, failure to disclose your status, to wear a condom was seen as risking someone else’s life, which is no longer the case,” he added.

In fact, “from the perspective of the kinds of impact that these laws have had on transmission, or risk, or behavior, what you find is that they really have no public health benefit and they have real public harms,” said Dr. Beyrer.

Claire Farel, MD, assistant professor and medical director of the UNC Infectious Diseases Clinic at the University of North Carolina at Chapel Hill, concurs. “Because of the criminalization undercurrent, there are people who don’t get tested, meaning that they are at risk for worse health outcomes, such as cancer, vascular disease, and of course HIV-related poor outcomes, including progression to AIDS.”

Farel also points to the residual stigma associated with HIV. “Much of this is inextricable from that surrounding homophobia, especially among young men of color who have sex with men. It opens up a larger conversation that a lot of people don’t want to engage in,” she said.
 

Laws broaden existing disparities even further

The CDC released a study June 4 showing substantial declines in the overall incidence of HIV in the United States, with an important caveat: There’s been a worsening disparity in cases. Access to care and engagement with care remain poor among certain populations. For example, Black individuals accounted for 41% of new HIV infections in 2019, but they represent only 12% of the U.S. population; Hispanic/Latinx persons accounted for 29% of new infections, although they represent only 17% of the entire population.

The same is true for HIV criminalization: In 2020, more than 50% of defendants were people of color, according to U.S. case data collated by the HIV Justice Network.

Still, the momentum to change these antiquated laws is gaining speed. In May, the Illinois State Senate passed a bill repealing HIV criminalization, and this past March, Virginia’s Governor Ralph Northam signed a bill lowering HIV-related criminalization charges from a felony to a misdemeanor and changing the wording of its law to include both intent and transmission.** California, Colorado, Iowa, Michigan, Nevada, and North Carolina have also modernized or repealed their laws.
 

Ending the U.S. HIV epidemic: Patients first

Without true HIV criminalization reform, efforts to change the public and clinical mindset regarding HIV from its being a highly stigmatized disease to a preventable, treatable infection are likely to fall short. Dr. Beyrer emphasized that the onus lies with the scientific and activist communities working together. “I don’t know how you can end the epidemic if you are still stigmatizing the people who are actually acquiring these infections,” he said.

There are steps that patients can take while these forces push for change.

“As people first process their diagnosis, they need to learn as much about HIV and the science behind it as possible,” advised Mr. Suttle. He said that to protect oneself, it’s essential to learn about HIV criminalization and the laws in one’s state.

“Find someone you can trust, starting with your medical provider if possible, and if you have a significant other, bring that person to your appointments so they can see that you are in care and doing all that you can do to lower viral loads and protect others,” he added.

Ms. Howell said that although people should be in treatment and care, attitudes also need to change on the clinician side. “We’re just given these meds, told to take them, and are sent on our merry ways, but they don’t tell us how to live our lives properly; nobody grabs us and says, hey, these are the laws and you need to know this or that.”

When a person who is HIV positive does get caught up in the system, if possible, that person should consult an attorney who understands these laws. Mr. Suttle suggested reaching out to organizations in the movement to end HIV criminalization (e.g., the Sero Project, the Center for HIV Law and Policy, or the Positive Women’s Network) for further support, help with cases (including providing experts to testify), social services, and other resources. Mr. Suttle also encourages people who need help and direction to reach out to him directly at [email protected].

Forty years ago, the CDC published its first report of an illness in five healthy gay men living in Los Angeles. The first cases in women were reported shortly thereafter. Over the years, there have been many scientific advances in prevention and treatment. But as Dr. Beyrer aptly noted in an editorial published January 2021 in The Lancet HIV, “time has not lessened the sting of the early decades of AIDS.”

“We should not have to be afraid of who we are because we are HIV positive,” said Ms. Howell.

Dr. Farel, Mr. Suttle, and Ms. Howell report no relevant financial relationships. Dr. Beyrer has a consulting agreement with Merck.
 

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

*Correction, 6/14/2021: An earlier version of this story misstated Ms. Howell's age. She is 40.

**Correction, 6/14/2021: An earlier version of this story misspelled Gov. Northam's name.

As summer approaches, so does the risk of Lyme disease.

According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.

Infection prevention

We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.

Diagnosis

Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.

Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.

For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.

The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.

As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As summer approaches, so does the risk of Lyme disease.

According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.

Infection prevention

We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.

Diagnosis

Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.

Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.

For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.

The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.

As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As summer approaches, so does the risk of Lyme disease.

According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.

Infection prevention

We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.

Diagnosis

Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.

Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.

For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.

The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.

As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.

Antibiotics are commonly overused for several viral respiratory conditions where antibiotic treatment is not clinically indicated. For example, a 2016 study by Fleming-Dutra and colleagues showed that at least 30% of all antibiotics prescribed in an outpatient setting were inappropriate and for acute bronchitis, antibiotic prescriptions were inappropriate in 50% of cases.¹ Acute bronchitis is predominantly a viral illness where antibiotics should be rarely used.^2-8 The Healthcare Effectiveness Data and Information Set has measured the avoidance of antibiotic treatment in adults with acute bronchitis since 2006. The National Committee for Quality Assurance reported in 2018 that about 75% of adults received antibiotics for acute bronchitis.⁹ Inappropriate antibiotic use contributes to antimicrobial resistance, resulting in the increase of morbidity and mortality of treatable infections.¹⁰ Reducing inappropriate antibiotic use in outpatient settings is a high-priority public health issue and is a Healthy People 2030 objective.¹¹

Antimicrobial Stewardship

Antimicrobial stewardship programs measure and track how antibiotics are prescribed by health care providers (HCPs) and used by patients. The Centers for Disease Control and Prevention (CDC) created a framework for outpatient antimicrobial stewardship programs by outlining 4 core elements: (1) commitment from every person involved in patient care to act as an antibiotic steward; (2) policies and interventions to promote appropriate antibiotic prescribing practices; (3) antibiotic prescription tracking and reporting; and (4) appropriate antibiotic use education.¹²

Audit and feedback (A&F) is a form of antibiotic prescription tracking and reporting that involves measuring and comparing a HCP’s performance (ie, antibiotic prescribing) with a standard, and the results of this audit are shared with the HCP. This strategy is based on the belief that a HCP is motivated to modify practice habits when given feedback showing that his or her performance is inconsistent with targeted expectations. A&F is most effective when feedback is provided by a supervisor or respected peer, presented more than once, individualized, delivered in both verbal and written formats, and includes explicit targets and an action plan.^13,14

This study focuses on an antimicrobial stewardship program implemented in an outpatient Indian Health Service ambulatory care clinic in the Pacific Northwest. The clinic was staffed by 9 HCPs serving about 12,000 American Indian and Alaskan Native patients. The clinic includes a full-service pharmacy where nearly all prescriptions issued by in-house HCPs are filled. The clinic’s antibiotic prescribing rate for adult patients with acute bronchitis was similar to the national mean in 2018 (75%).⁹ The study objective was to reduce the rate of potentially inappropriate (not guideline-concordant) antibiotic prescribing in patients with acute bronchitis without underlying chronic lung disease or evidence of bacterial infection through A&F.

Methods

The antimicrobial stewardship program was implemented by 3 pharmacists, including a pharmacy resident. HCPs received education by pharmacy staff on evidence-based prescribing for adult acute bronchitis and quarterly feedback on antibiotic prescribing rates. All prescribing and dispensing records necessary for the program were available in the clinic electronic health record. The rate of potentially inappropriate antibiotic prescribing was calculated as the proportion of eligible bronchitis cases who received antibiotics.

In October 2018, a 60-minute educational session was provided by 2 pharmacists to HCPs. The material covered an overview of acute bronchitis presentation, diagnosis, treatment (Table 1), and a comparison of national and local prescribing data (baseline audit).^2-4 The educational session concluded with prescription strategies to reduce inappropriate antibiotic prescribing, including but not limited to: delayed prescriptions, patient and caregiver education, use of nonantibiotic medications to control symptoms, and use of A&F reports.^5-8 At the conclusion of the session, HCPs committed to engage in the antimicrobial stewardship program.

Audit

To determine the total number of eligible bronchitis cases (denominator), a visit report was generated by a pharmacist for a primary diagnosis of acute bronchitis using International Statistical Classification of Diseases, Tenth Revision (ICD 10) codes (J20.3 - J20.9) for the review period. Only adults aged ≥ 18 years were included. Patients with a chronic lung disease (eg, chronic obstructive pulmonary disease, asthma) and those who had a concomitant bacterial infection (eg, urinary tract infection, cellulitis) were excluded. A visit for acute bronchitis that included additional ICD 10 codes indicating the patient had a chronic lung disease or concomitant bacterial infection were used to determine exclusion. The remaining patients who received a potentially inappropriate antibiotic prescription (numerator) were those who were prescribed or dispensed antibiotics on the date of service.

Feedback

Baseline data were presented to HCPs during the educational session in October 2018. Prospective audits were performed quarterly thereafter (January, April, and July) by the pharmacy resident using the criteria described above. Audit data were compiled into personalized reports and provided to HCPs by the pharmacy resident with written and verbal individual feedback. Written feedback was sent by email to each HCP containing the HCP’s rate, the clinic rate in aggregate, rates from the prior year and quarter(s) for comparison, and clinical pearls from the guidelines (Figure). Verbal feedback included a review of the written feedback and answering any questions concerning the report.

Implementation

Study periods were chosen to coincide with the pharmacy residency training year, which starts in July and ends in June. The start date of October 2018 differed from the start of the residency year (July 2018) owing to delays in obtaining permissions. A&F and analysis of prescribing rates continued through the end of the residency year, for total duration of 9 months (October 1, 2018 to June 30, 2019). For ease of reporting, quarterly reports followed the federal government’s fiscal year (FY) which runs from October 1 of the prior calendar year through September 30 of the year being described. HCPs received 4 feedback reports: baseline (October 1, 2018 - June 30, 2018) in October 2018, quarter 1 (October 1, 2018 - December 31, 2018) in January 2019, quarter 2 (January 1, 2019 - March 31, 2019) in April 2019, and quarter 3 (April 1, 2019 - June 30, 2019) in July 2019.

Statistical Analysis

Prescribing rates were compared between identical 9 -month periods. A 2-sample binomial test for proportions was used to derive an approximate CI of prescribing rates at the patient level. However, to account for clustering of patients within HCP panels and dependence of observations over study periods stemming from examining the same HCPs within each of the periods, the Wilcoxon signed rank test for paired data was used to evaluate prescribing rates at the HCP level. Statistical analysis was performed using R statistical software version 4.0.3. Differences were considered significant at P < .05 set a priori.

This study was approved by the Portland Area Indian Health Service Institutional Review Board (Study ID: 1316730).

Results

All 9 HCPs who see adult patients at the clinic agreed to participate and were all fully present in each study period. Among HCPs, there were 5 physicians and 4 physician assistants or nurse practitioners. There was a total of 213 visits that met study criteria during the baseline period (October 1, 2017 to June 30, 2018) and 177 visits in the posteducation period (October 1, 2018 to June 30, 2019). The total number of acute bronchitis encounters varied by HCP (Ranges, 5-63 [baseline] and 2-57 [posteducation]); however, the relative number of encounters each HCP contributed was similar in each study period (Table 2). The pharmacy resident spent about 2 hours each quarter to generate 9 feedback reports, 1 for each HCP.

Antibiotic Prescribing

Antibiotic prescribing rates decreased from 75% at baseline to 60% at posteducation month 9 (absolute difference, -15% [95% CI, 5 - 24%]; P ≤ .01) (Table 3). The clinic rate was lower for each quarter in FY 2019 (posteducation) compared with the same quarter of FY 2018 (baseline), with the lowest rate observed in the final quarter of the study. Comparing pre- and post- A&F, the rates for HCPs prescribing antibiotics were lower for 7 HCPs, unchanged for 1 HCP, and slightly increased for 1 HCP(P = .02).

Discussion

Acute bronchitis remains a common diagnosis where antibiotics are prescribed despite being a predominately viral illness. Guidelines and evidence-based practices advise against antibiotics for this diagnosis. According to the American Academy of Family Physicians, antibiotics are reserved for cases where chronic lung disease is present as these patients are at a high risk of developing pneumonia.³ The decision to prescribe antibiotics is complex and driven by several interdependent factors, such as patient expectations, health system limitations, clinician training, and specialty.¹⁵ HCPs may more aggressively treat acute bronchitis among American Indian/Alaskan Native (AI/AN) people due to a high risk of developing serious complications from respiratory illnesses.¹⁶ A clinician’s background, usual patient cohort (ie, mostly pediatric or geriatric), and time spent in urgent care or in activities outside of patient care (administration) may account for the difference in patient encounters by HCP for acute bronchitis.

Following the CDC framework, this antimicrobial stewardship program helped empower people involved in patient care (eg, pharmacists, HCPs), educate staff on proper use of antibiotics for acute bronchitis, and track and report antibiotic prescribing through the A&F process. Educational interventions coupled with ongoing A&F are reproducible by other health care facilities and are not usually time consuming. This study showcases a successful example of implementing A&F in an antimicrobial stewardship quality improvement project that could be translated toward other conditions (eg, sinusitis, urinary tract infection, community-acquired pneumonia).

In a similar study, Meeker and colleagues used a variation of an A&F intervention using a monthly email showing peer comparisons to notify clinicians who were prescribing too many unnecessary antibiotics for common respiratory illnesses that did not require antibiotics, such as the common cold.¹⁷ The peer comparison intervention arm emailed a rank order that listed prescribers by the number of prescriptions for common respiratory illnesses. This intervention demonstrated a reduction of 5.2% in inappropriate antibiotic prescribing.

Limitations

This quality improvement study had several limitations. The study did not account for the duration of symptoms as a factor to judge appropriateness. Although this was identified early in the study, it was unavoidable since there was no report that could extract the duration of symptoms in the electronic health record. Future studies should consider a manual review of each encounter to overcome this limitation. Another limitation was that only three-quarters of the year and not the entire year were reviewed. Future studies should include longer time frames to measure the durability of changes to antibiotic prescriptions. Lastly, the study did not assess diagnosis shifting (the practice of changing the proportion of antibiotic-appropriate acute respiratory tract infection diagnosis over time), effects of patient demographics (patient age and sex were not recorded), or any sustained effect on prescribing rates after the study ended.

Conclusions

Clinician education coupled with A&F are components of the CDC’s framework for an effective antimicrobial stewardship program. The intervention seem to be an effective means toward reducing inappropriate antibiotic prescribing for acute bronchitis and has the potential for application to other antimicrobial stewardship initiatives. The present study adds to the growing body of evidence on the importance and impact an antimicrobial stewardship program has on a clinic or health system.

Acknowledgment

The results of this study have been reported at the 2019 IHS Southwest Regional Pharmacy Continuing Education Seminar, April 12-14, 2019.

Antibiotics are commonly overused for several viral respiratory conditions where antibiotic treatment is not clinically indicated. For example, a 2016 study by Fleming-Dutra and colleagues showed that at least 30% of all antibiotics prescribed in an outpatient setting were inappropriate and for acute bronchitis, antibiotic prescriptions were inappropriate in 50% of cases.¹ Acute bronchitis is predominantly a viral illness where antibiotics should be rarely used.^2-8 The Healthcare Effectiveness Data and Information Set has measured the avoidance of antibiotic treatment in adults with acute bronchitis since 2006. The National Committee for Quality Assurance reported in 2018 that about 75% of adults received antibiotics for acute bronchitis.⁹ Inappropriate antibiotic use contributes to antimicrobial resistance, resulting in the increase of morbidity and mortality of treatable infections.¹⁰ Reducing inappropriate antibiotic use in outpatient settings is a high-priority public health issue and is a Healthy People 2030 objective.¹¹

Antimicrobial Stewardship

Antimicrobial stewardship programs measure and track how antibiotics are prescribed by health care providers (HCPs) and used by patients. The Centers for Disease Control and Prevention (CDC) created a framework for outpatient antimicrobial stewardship programs by outlining 4 core elements: (1) commitment from every person involved in patient care to act as an antibiotic steward; (2) policies and interventions to promote appropriate antibiotic prescribing practices; (3) antibiotic prescription tracking and reporting; and (4) appropriate antibiotic use education.¹²

Audit and feedback (A&F) is a form of antibiotic prescription tracking and reporting that involves measuring and comparing a HCP’s performance (ie, antibiotic prescribing) with a standard, and the results of this audit are shared with the HCP. This strategy is based on the belief that a HCP is motivated to modify practice habits when given feedback showing that his or her performance is inconsistent with targeted expectations. A&F is most effective when feedback is provided by a supervisor or respected peer, presented more than once, individualized, delivered in both verbal and written formats, and includes explicit targets and an action plan.^13,14

This study focuses on an antimicrobial stewardship program implemented in an outpatient Indian Health Service ambulatory care clinic in the Pacific Northwest. The clinic was staffed by 9 HCPs serving about 12,000 American Indian and Alaskan Native patients. The clinic includes a full-service pharmacy where nearly all prescriptions issued by in-house HCPs are filled. The clinic’s antibiotic prescribing rate for adult patients with acute bronchitis was similar to the national mean in 2018 (75%).⁹ The study objective was to reduce the rate of potentially inappropriate (not guideline-concordant) antibiotic prescribing in patients with acute bronchitis without underlying chronic lung disease or evidence of bacterial infection through A&F.

Methods

The antimicrobial stewardship program was implemented by 3 pharmacists, including a pharmacy resident. HCPs received education by pharmacy staff on evidence-based prescribing for adult acute bronchitis and quarterly feedback on antibiotic prescribing rates. All prescribing and dispensing records necessary for the program were available in the clinic electronic health record. The rate of potentially inappropriate antibiotic prescribing was calculated as the proportion of eligible bronchitis cases who received antibiotics.

In October 2018, a 60-minute educational session was provided by 2 pharmacists to HCPs. The material covered an overview of acute bronchitis presentation, diagnosis, treatment (Table 1), and a comparison of national and local prescribing data (baseline audit).^2-4 The educational session concluded with prescription strategies to reduce inappropriate antibiotic prescribing, including but not limited to: delayed prescriptions, patient and caregiver education, use of nonantibiotic medications to control symptoms, and use of A&F reports.^5-8 At the conclusion of the session, HCPs committed to engage in the antimicrobial stewardship program.

Audit

To determine the total number of eligible bronchitis cases (denominator), a visit report was generated by a pharmacist for a primary diagnosis of acute bronchitis using International Statistical Classification of Diseases, Tenth Revision (ICD 10) codes (J20.3 - J20.9) for the review period. Only adults aged ≥ 18 years were included. Patients with a chronic lung disease (eg, chronic obstructive pulmonary disease, asthma) and those who had a concomitant bacterial infection (eg, urinary tract infection, cellulitis) were excluded. A visit for acute bronchitis that included additional ICD 10 codes indicating the patient had a chronic lung disease or concomitant bacterial infection were used to determine exclusion. The remaining patients who received a potentially inappropriate antibiotic prescription (numerator) were those who were prescribed or dispensed antibiotics on the date of service.

Feedback

Baseline data were presented to HCPs during the educational session in October 2018. Prospective audits were performed quarterly thereafter (January, April, and July) by the pharmacy resident using the criteria described above. Audit data were compiled into personalized reports and provided to HCPs by the pharmacy resident with written and verbal individual feedback. Written feedback was sent by email to each HCP containing the HCP’s rate, the clinic rate in aggregate, rates from the prior year and quarter(s) for comparison, and clinical pearls from the guidelines (Figure). Verbal feedback included a review of the written feedback and answering any questions concerning the report.

Implementation

Study periods were chosen to coincide with the pharmacy residency training year, which starts in July and ends in June. The start date of October 2018 differed from the start of the residency year (July 2018) owing to delays in obtaining permissions. A&F and analysis of prescribing rates continued through the end of the residency year, for total duration of 9 months (October 1, 2018 to June 30, 2019). For ease of reporting, quarterly reports followed the federal government’s fiscal year (FY) which runs from October 1 of the prior calendar year through September 30 of the year being described. HCPs received 4 feedback reports: baseline (October 1, 2018 - June 30, 2018) in October 2018, quarter 1 (October 1, 2018 - December 31, 2018) in January 2019, quarter 2 (January 1, 2019 - March 31, 2019) in April 2019, and quarter 3 (April 1, 2019 - June 30, 2019) in July 2019.

Statistical Analysis

Prescribing rates were compared between identical 9 -month periods. A 2-sample binomial test for proportions was used to derive an approximate CI of prescribing rates at the patient level. However, to account for clustering of patients within HCP panels and dependence of observations over study periods stemming from examining the same HCPs within each of the periods, the Wilcoxon signed rank test for paired data was used to evaluate prescribing rates at the HCP level. Statistical analysis was performed using R statistical software version 4.0.3. Differences were considered significant at P < .05 set a priori.

This study was approved by the Portland Area Indian Health Service Institutional Review Board (Study ID: 1316730).

Results

All 9 HCPs who see adult patients at the clinic agreed to participate and were all fully present in each study period. Among HCPs, there were 5 physicians and 4 physician assistants or nurse practitioners. There was a total of 213 visits that met study criteria during the baseline period (October 1, 2017 to June 30, 2018) and 177 visits in the posteducation period (October 1, 2018 to June 30, 2019). The total number of acute bronchitis encounters varied by HCP (Ranges, 5-63 [baseline] and 2-57 [posteducation]); however, the relative number of encounters each HCP contributed was similar in each study period (Table 2). The pharmacy resident spent about 2 hours each quarter to generate 9 feedback reports, 1 for each HCP.

Antibiotic Prescribing

Antibiotic prescribing rates decreased from 75% at baseline to 60% at posteducation month 9 (absolute difference, -15% [95% CI, 5 - 24%]; P ≤ .01) (Table 3). The clinic rate was lower for each quarter in FY 2019 (posteducation) compared with the same quarter of FY 2018 (baseline), with the lowest rate observed in the final quarter of the study. Comparing pre- and post- A&F, the rates for HCPs prescribing antibiotics were lower for 7 HCPs, unchanged for 1 HCP, and slightly increased for 1 HCP(P = .02).

Discussion

Acute bronchitis remains a common diagnosis where antibiotics are prescribed despite being a predominately viral illness. Guidelines and evidence-based practices advise against antibiotics for this diagnosis. According to the American Academy of Family Physicians, antibiotics are reserved for cases where chronic lung disease is present as these patients are at a high risk of developing pneumonia.³ The decision to prescribe antibiotics is complex and driven by several interdependent factors, such as patient expectations, health system limitations, clinician training, and specialty.¹⁵ HCPs may more aggressively treat acute bronchitis among American Indian/Alaskan Native (AI/AN) people due to a high risk of developing serious complications from respiratory illnesses.¹⁶ A clinician’s background, usual patient cohort (ie, mostly pediatric or geriatric), and time spent in urgent care or in activities outside of patient care (administration) may account for the difference in patient encounters by HCP for acute bronchitis.

Following the CDC framework, this antimicrobial stewardship program helped empower people involved in patient care (eg, pharmacists, HCPs), educate staff on proper use of antibiotics for acute bronchitis, and track and report antibiotic prescribing through the A&F process. Educational interventions coupled with ongoing A&F are reproducible by other health care facilities and are not usually time consuming. This study showcases a successful example of implementing A&F in an antimicrobial stewardship quality improvement project that could be translated toward other conditions (eg, sinusitis, urinary tract infection, community-acquired pneumonia).

In a similar study, Meeker and colleagues used a variation of an A&F intervention using a monthly email showing peer comparisons to notify clinicians who were prescribing too many unnecessary antibiotics for common respiratory illnesses that did not require antibiotics, such as the common cold.¹⁷ The peer comparison intervention arm emailed a rank order that listed prescribers by the number of prescriptions for common respiratory illnesses. This intervention demonstrated a reduction of 5.2% in inappropriate antibiotic prescribing.

Limitations

This quality improvement study had several limitations. The study did not account for the duration of symptoms as a factor to judge appropriateness. Although this was identified early in the study, it was unavoidable since there was no report that could extract the duration of symptoms in the electronic health record. Future studies should consider a manual review of each encounter to overcome this limitation. Another limitation was that only three-quarters of the year and not the entire year were reviewed. Future studies should include longer time frames to measure the durability of changes to antibiotic prescriptions. Lastly, the study did not assess diagnosis shifting (the practice of changing the proportion of antibiotic-appropriate acute respiratory tract infection diagnosis over time), effects of patient demographics (patient age and sex were not recorded), or any sustained effect on prescribing rates after the study ended.

Conclusions

Clinician education coupled with A&F are components of the CDC’s framework for an effective antimicrobial stewardship program. The intervention seem to be an effective means toward reducing inappropriate antibiotic prescribing for acute bronchitis and has the potential for application to other antimicrobial stewardship initiatives. The present study adds to the growing body of evidence on the importance and impact an antimicrobial stewardship program has on a clinic or health system.

Acknowledgment

The results of this study have been reported at the 2019 IHS Southwest Regional Pharmacy Continuing Education Seminar, April 12-14, 2019.

Antibiotics are commonly overused for several viral respiratory conditions where antibiotic treatment is not clinically indicated. For example, a 2016 study by Fleming-Dutra and colleagues showed that at least 30% of all antibiotics prescribed in an outpatient setting were inappropriate and for acute bronchitis, antibiotic prescriptions were inappropriate in 50% of cases.¹ Acute bronchitis is predominantly a viral illness where antibiotics should be rarely used.^2-8 The Healthcare Effectiveness Data and Information Set has measured the avoidance of antibiotic treatment in adults with acute bronchitis since 2006. The National Committee for Quality Assurance reported in 2018 that about 75% of adults received antibiotics for acute bronchitis.⁹ Inappropriate antibiotic use contributes to antimicrobial resistance, resulting in the increase of morbidity and mortality of treatable infections.¹⁰ Reducing inappropriate antibiotic use in outpatient settings is a high-priority public health issue and is a Healthy People 2030 objective.¹¹

Antimicrobial Stewardship

Antimicrobial stewardship programs measure and track how antibiotics are prescribed by health care providers (HCPs) and used by patients. The Centers for Disease Control and Prevention (CDC) created a framework for outpatient antimicrobial stewardship programs by outlining 4 core elements: (1) commitment from every person involved in patient care to act as an antibiotic steward; (2) policies and interventions to promote appropriate antibiotic prescribing practices; (3) antibiotic prescription tracking and reporting; and (4) appropriate antibiotic use education.¹²

Audit and feedback (A&F) is a form of antibiotic prescription tracking and reporting that involves measuring and comparing a HCP’s performance (ie, antibiotic prescribing) with a standard, and the results of this audit are shared with the HCP. This strategy is based on the belief that a HCP is motivated to modify practice habits when given feedback showing that his or her performance is inconsistent with targeted expectations. A&F is most effective when feedback is provided by a supervisor or respected peer, presented more than once, individualized, delivered in both verbal and written formats, and includes explicit targets and an action plan.^13,14

This study focuses on an antimicrobial stewardship program implemented in an outpatient Indian Health Service ambulatory care clinic in the Pacific Northwest. The clinic was staffed by 9 HCPs serving about 12,000 American Indian and Alaskan Native patients. The clinic includes a full-service pharmacy where nearly all prescriptions issued by in-house HCPs are filled. The clinic’s antibiotic prescribing rate for adult patients with acute bronchitis was similar to the national mean in 2018 (75%).⁹ The study objective was to reduce the rate of potentially inappropriate (not guideline-concordant) antibiotic prescribing in patients with acute bronchitis without underlying chronic lung disease or evidence of bacterial infection through A&F.

Methods

The antimicrobial stewardship program was implemented by 3 pharmacists, including a pharmacy resident. HCPs received education by pharmacy staff on evidence-based prescribing for adult acute bronchitis and quarterly feedback on antibiotic prescribing rates. All prescribing and dispensing records necessary for the program were available in the clinic electronic health record. The rate of potentially inappropriate antibiotic prescribing was calculated as the proportion of eligible bronchitis cases who received antibiotics.

In October 2018, a 60-minute educational session was provided by 2 pharmacists to HCPs. The material covered an overview of acute bronchitis presentation, diagnosis, treatment (Table 1), and a comparison of national and local prescribing data (baseline audit).^2-4 The educational session concluded with prescription strategies to reduce inappropriate antibiotic prescribing, including but not limited to: delayed prescriptions, patient and caregiver education, use of nonantibiotic medications to control symptoms, and use of A&F reports.^5-8 At the conclusion of the session, HCPs committed to engage in the antimicrobial stewardship program.

Audit

To determine the total number of eligible bronchitis cases (denominator), a visit report was generated by a pharmacist for a primary diagnosis of acute bronchitis using International Statistical Classification of Diseases, Tenth Revision (ICD 10) codes (J20.3 - J20.9) for the review period. Only adults aged ≥ 18 years were included. Patients with a chronic lung disease (eg, chronic obstructive pulmonary disease, asthma) and those who had a concomitant bacterial infection (eg, urinary tract infection, cellulitis) were excluded. A visit for acute bronchitis that included additional ICD 10 codes indicating the patient had a chronic lung disease or concomitant bacterial infection were used to determine exclusion. The remaining patients who received a potentially inappropriate antibiotic prescription (numerator) were those who were prescribed or dispensed antibiotics on the date of service.

Feedback

Baseline data were presented to HCPs during the educational session in October 2018. Prospective audits were performed quarterly thereafter (January, April, and July) by the pharmacy resident using the criteria described above. Audit data were compiled into personalized reports and provided to HCPs by the pharmacy resident with written and verbal individual feedback. Written feedback was sent by email to each HCP containing the HCP’s rate, the clinic rate in aggregate, rates from the prior year and quarter(s) for comparison, and clinical pearls from the guidelines (Figure). Verbal feedback included a review of the written feedback and answering any questions concerning the report.

Implementation

Study periods were chosen to coincide with the pharmacy residency training year, which starts in July and ends in June. The start date of October 2018 differed from the start of the residency year (July 2018) owing to delays in obtaining permissions. A&F and analysis of prescribing rates continued through the end of the residency year, for total duration of 9 months (October 1, 2018 to June 30, 2019). For ease of reporting, quarterly reports followed the federal government’s fiscal year (FY) which runs from October 1 of the prior calendar year through September 30 of the year being described. HCPs received 4 feedback reports: baseline (October 1, 2018 - June 30, 2018) in October 2018, quarter 1 (October 1, 2018 - December 31, 2018) in January 2019, quarter 2 (January 1, 2019 - March 31, 2019) in April 2019, and quarter 3 (April 1, 2019 - June 30, 2019) in July 2019.

Statistical Analysis

Prescribing rates were compared between identical 9 -month periods. A 2-sample binomial test for proportions was used to derive an approximate CI of prescribing rates at the patient level. However, to account for clustering of patients within HCP panels and dependence of observations over study periods stemming from examining the same HCPs within each of the periods, the Wilcoxon signed rank test for paired data was used to evaluate prescribing rates at the HCP level. Statistical analysis was performed using R statistical software version 4.0.3. Differences were considered significant at P < .05 set a priori.

This study was approved by the Portland Area Indian Health Service Institutional Review Board (Study ID: 1316730).

Results

All 9 HCPs who see adult patients at the clinic agreed to participate and were all fully present in each study period. Among HCPs, there were 5 physicians and 4 physician assistants or nurse practitioners. There was a total of 213 visits that met study criteria during the baseline period (October 1, 2017 to June 30, 2018) and 177 visits in the posteducation period (October 1, 2018 to June 30, 2019). The total number of acute bronchitis encounters varied by HCP (Ranges, 5-63 [baseline] and 2-57 [posteducation]); however, the relative number of encounters each HCP contributed was similar in each study period (Table 2). The pharmacy resident spent about 2 hours each quarter to generate 9 feedback reports, 1 for each HCP.

Antibiotic Prescribing

Antibiotic prescribing rates decreased from 75% at baseline to 60% at posteducation month 9 (absolute difference, -15% [95% CI, 5 - 24%]; P ≤ .01) (Table 3). The clinic rate was lower for each quarter in FY 2019 (posteducation) compared with the same quarter of FY 2018 (baseline), with the lowest rate observed in the final quarter of the study. Comparing pre- and post- A&F, the rates for HCPs prescribing antibiotics were lower for 7 HCPs, unchanged for 1 HCP, and slightly increased for 1 HCP(P = .02).

Discussion

Acute bronchitis remains a common diagnosis where antibiotics are prescribed despite being a predominately viral illness. Guidelines and evidence-based practices advise against antibiotics for this diagnosis. According to the American Academy of Family Physicians, antibiotics are reserved for cases where chronic lung disease is present as these patients are at a high risk of developing pneumonia.³ The decision to prescribe antibiotics is complex and driven by several interdependent factors, such as patient expectations, health system limitations, clinician training, and specialty.¹⁵ HCPs may more aggressively treat acute bronchitis among American Indian/Alaskan Native (AI/AN) people due to a high risk of developing serious complications from respiratory illnesses.¹⁶ A clinician’s background, usual patient cohort (ie, mostly pediatric or geriatric), and time spent in urgent care or in activities outside of patient care (administration) may account for the difference in patient encounters by HCP for acute bronchitis.

Following the CDC framework, this antimicrobial stewardship program helped empower people involved in patient care (eg, pharmacists, HCPs), educate staff on proper use of antibiotics for acute bronchitis, and track and report antibiotic prescribing through the A&F process. Educational interventions coupled with ongoing A&F are reproducible by other health care facilities and are not usually time consuming. This study showcases a successful example of implementing A&F in an antimicrobial stewardship quality improvement project that could be translated toward other conditions (eg, sinusitis, urinary tract infection, community-acquired pneumonia).

In a similar study, Meeker and colleagues used a variation of an A&F intervention using a monthly email showing peer comparisons to notify clinicians who were prescribing too many unnecessary antibiotics for common respiratory illnesses that did not require antibiotics, such as the common cold.¹⁷ The peer comparison intervention arm emailed a rank order that listed prescribers by the number of prescriptions for common respiratory illnesses. This intervention demonstrated a reduction of 5.2% in inappropriate antibiotic prescribing.

Limitations

This quality improvement study had several limitations. The study did not account for the duration of symptoms as a factor to judge appropriateness. Although this was identified early in the study, it was unavoidable since there was no report that could extract the duration of symptoms in the electronic health record. Future studies should consider a manual review of each encounter to overcome this limitation. Another limitation was that only three-quarters of the year and not the entire year were reviewed. Future studies should include longer time frames to measure the durability of changes to antibiotic prescriptions. Lastly, the study did not assess diagnosis shifting (the practice of changing the proportion of antibiotic-appropriate acute respiratory tract infection diagnosis over time), effects of patient demographics (patient age and sex were not recorded), or any sustained effect on prescribing rates after the study ended.

Conclusions

Clinician education coupled with A&F are components of the CDC’s framework for an effective antimicrobial stewardship program. The intervention seem to be an effective means toward reducing inappropriate antibiotic prescribing for acute bronchitis and has the potential for application to other antimicrobial stewardship initiatives. The present study adds to the growing body of evidence on the importance and impact an antimicrobial stewardship program has on a clinic or health system.

Acknowledgment

The results of this study have been reported at the 2019 IHS Southwest Regional Pharmacy Continuing Education Seminar, April 12-14, 2019.

Over 6.3 million doses of COVID-19 vaccine have been administered to children aged 12-17 years as of June 7, according to data from the Centers for Disease Control and Prevention.

The latest results from the CDC’s COVID Data Tracker show that 22.5% of all U.S. children aged 12-15 years have received at least one dose of a vaccine, compared with 38.1% of those aged 16-17, with the corresponding figures for vaccine completion coming in at 4.1% and 26.4%. Compared with a week earlier, those numbers are up by 15.4% (one dose) and 486% (completion) for the younger group and by 4.7% and 8.6%, respectively, for the older children.

Children aged 12-15 represented 17.9% of all persons who initiated vaccination in the last 14 days up to June 7, while children aged 16-17 made up 4.8% of vaccine initiation over that period. The 25- to 39-year-olds, at 23.7% of all vaccine initiators, were the only group ahead of those aged 12-15, and the 50- to 64-year-olds were just behind at 17.7%, the CDC data show.

Both groups of children were on the low side, however, when it came to vaccine completion in the last 14 days, with those aged 12-15 at 6.7% of the total and those aged 16-17 years at 4.3%. The only age groups lower than that were ≥75 at 3.5% and <12 at 0.2%, and the highest share of vaccine completion was 26.0% for those aged 25-39, which also happens to be the group with the largest share of the U.S. population (20.5%), the CDC said.

People considered fully vaccinated are those who have received the second dose of a two-dose series or one dose of a single-shot vaccine, but children under age 18 years are eligible only for the Pfizer-BioNTech version, the CDC noted.

Meanwhile, back on the incidence side of the COVID-19 pandemic, the number of new cases in U.S. children for the week ending June 3 was at its lowest point (16,281) since mid-June of 2020, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Cases among children now total 3.99 million, which represents 14.1% of cases among all ages, a proportion that hasn’t increased since mid-May, which hasn’t happened since the two groups started keeping track in mid-April of 2020 in the 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam that report such data by age.

Less encouraging was the CDC’s report that “COVID-19-associated hospitalization rates among adolescents ages 12-17 years increased during March and April, following declines in January and February 2021.”

Children have been experiencing much lower rates of severe disease than those of adults throughout the pandemic, the CDC pointed out, but “recent increases in COVID-19-associated hospitalization rates and the potential for severe disease in adolescents reinforce the importance of continued prevention strategies, including vaccination and the correct and consistent use of masks in those who are not yet fully vaccinated.”

[email protected]

Over 6.3 million doses of COVID-19 vaccine have been administered to children aged 12-17 years as of June 7, according to data from the Centers for Disease Control and Prevention.

The latest results from the CDC’s COVID Data Tracker show that 22.5% of all U.S. children aged 12-15 years have received at least one dose of a vaccine, compared with 38.1% of those aged 16-17, with the corresponding figures for vaccine completion coming in at 4.1% and 26.4%. Compared with a week earlier, those numbers are up by 15.4% (one dose) and 486% (completion) for the younger group and by 4.7% and 8.6%, respectively, for the older children.

Children aged 12-15 represented 17.9% of all persons who initiated vaccination in the last 14 days up to June 7, while children aged 16-17 made up 4.8% of vaccine initiation over that period. The 25- to 39-year-olds, at 23.7% of all vaccine initiators, were the only group ahead of those aged 12-15, and the 50- to 64-year-olds were just behind at 17.7%, the CDC data show.

Both groups of children were on the low side, however, when it came to vaccine completion in the last 14 days, with those aged 12-15 at 6.7% of the total and those aged 16-17 years at 4.3%. The only age groups lower than that were ≥75 at 3.5% and <12 at 0.2%, and the highest share of vaccine completion was 26.0% for those aged 25-39, which also happens to be the group with the largest share of the U.S. population (20.5%), the CDC said.

People considered fully vaccinated are those who have received the second dose of a two-dose series or one dose of a single-shot vaccine, but children under age 18 years are eligible only for the Pfizer-BioNTech version, the CDC noted.

Meanwhile, back on the incidence side of the COVID-19 pandemic, the number of new cases in U.S. children for the week ending June 3 was at its lowest point (16,281) since mid-June of 2020, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Cases among children now total 3.99 million, which represents 14.1% of cases among all ages, a proportion that hasn’t increased since mid-May, which hasn’t happened since the two groups started keeping track in mid-April of 2020 in the 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam that report such data by age.

Less encouraging was the CDC’s report that “COVID-19-associated hospitalization rates among adolescents ages 12-17 years increased during March and April, following declines in January and February 2021.”

Children have been experiencing much lower rates of severe disease than those of adults throughout the pandemic, the CDC pointed out, but “recent increases in COVID-19-associated hospitalization rates and the potential for severe disease in adolescents reinforce the importance of continued prevention strategies, including vaccination and the correct and consistent use of masks in those who are not yet fully vaccinated.”

[email protected]

Over 6.3 million doses of COVID-19 vaccine have been administered to children aged 12-17 years as of June 7, according to data from the Centers for Disease Control and Prevention.

The latest results from the CDC’s COVID Data Tracker show that 22.5% of all U.S. children aged 12-15 years have received at least one dose of a vaccine, compared with 38.1% of those aged 16-17, with the corresponding figures for vaccine completion coming in at 4.1% and 26.4%. Compared with a week earlier, those numbers are up by 15.4% (one dose) and 486% (completion) for the younger group and by 4.7% and 8.6%, respectively, for the older children.

Children aged 12-15 represented 17.9% of all persons who initiated vaccination in the last 14 days up to June 7, while children aged 16-17 made up 4.8% of vaccine initiation over that period. The 25- to 39-year-olds, at 23.7% of all vaccine initiators, were the only group ahead of those aged 12-15, and the 50- to 64-year-olds were just behind at 17.7%, the CDC data show.

Both groups of children were on the low side, however, when it came to vaccine completion in the last 14 days, with those aged 12-15 at 6.7% of the total and those aged 16-17 years at 4.3%. The only age groups lower than that were ≥75 at 3.5% and <12 at 0.2%, and the highest share of vaccine completion was 26.0% for those aged 25-39, which also happens to be the group with the largest share of the U.S. population (20.5%), the CDC said.

People considered fully vaccinated are those who have received the second dose of a two-dose series or one dose of a single-shot vaccine, but children under age 18 years are eligible only for the Pfizer-BioNTech version, the CDC noted.

Meanwhile, back on the incidence side of the COVID-19 pandemic, the number of new cases in U.S. children for the week ending June 3 was at its lowest point (16,281) since mid-June of 2020, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Cases among children now total 3.99 million, which represents 14.1% of cases among all ages, a proportion that hasn’t increased since mid-May, which hasn’t happened since the two groups started keeping track in mid-April of 2020 in the 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam that report such data by age.

Less encouraging was the CDC’s report that “COVID-19-associated hospitalization rates among adolescents ages 12-17 years increased during March and April, following declines in January and February 2021.”

Children have been experiencing much lower rates of severe disease than those of adults throughout the pandemic, the CDC pointed out, but “recent increases in COVID-19-associated hospitalization rates and the potential for severe disease in adolescents reinforce the importance of continued prevention strategies, including vaccination and the correct and consistent use of masks in those who are not yet fully vaccinated.”

[email protected]