Pediatric News

The Tiger Woods saga, which has been broadcast on HBO, is a “child” of the ESPN Michael Jordan series – which riveted early pandemic America. It is likely to exert a similar vicelike hold on the imagination of Biden transition/Trump impeachment II United States, despite not having the express participation of Woods himself.

The differences in parenting styles of these young African American men, at least superficially, appears in amazingly stark contrast.

Whereas Michael Jordan’s parents appear to have shown good old, red-blooded North Carolina ambitious and hard-driven tough parenting, Earl and Kultida Woods seem to have exerted a textbook example of what we call “achievement by proxy distortion” (ABPD) parenting style.^1-5

By deciding, even prior to birth, what their son’s future career would be, Earl, aided by Kultida Woods, created a master plan that came to fruition when Eldrick Tont “Tiger” Woods won his first Masters Tournament at the ripe old age of 21.

His parents’ fine-tuning of the ABPD template for professional sports parenting is often emulated. It had been earlier developed, in an industrial model – especially in women’s gymnastics – where Bela Karolyi and others in the Romanian Eastern Bloc system had developed Nadia Comaneci and others to be prepubescent superstars of the 1970s. When it was transferred to the more financially supportive, fertile base of the U.S., physical and sexual abuse were the acceptable price paid for Olympic gold medals.

When Tiger first appeared on the U.S. radar at the age of 2 on the Mike Douglas show in 1977, he was already definitively on the way to “prodigy” territory. Earl, a retired Vietnam veteran and product of the U.S. Marines, was able to model his own extraordinarily rigorous training where breaking down soldiers psychologically helps them survive special ops behind enemy lines. He trained his son essentially from birth, imprinting through somatic and postural echo these golf skills and habits for playing under pressure, handling annoying distraction, and self-hypnosis. These all clearly accelerated his son’s ability to enter the “zone,” a level of high attunement required, even demanded, at the highest levels of professional golf.

His parents’ ruthless approach, clearly accompanied by undoubted love and enthusiasm, to ending what appears to have been an age-appropriate high school relationship with his then “sweetheart,” appears on the surface a little cruel. But their approach achieved its purpose of sacrificing a distraction on the glorious golden path toward inevitable success and superstardom. This likely also produced a degree of self-objectification and further compartmentalization.

The typical outcome of ABPD is a fairly unidimensional identity defined by the activity, or in this case, the sport. In this case, where Earl was building or imagining a Messianic role for Tiger, multidimensionality was important as the self-described “Cablinasian” moniker suggests, whereby all of Tiger’s background of Caucasian, Black, Indian, and Asian ancestry was acknowledged as they all became lifelong fans.

What most likely saved Tiger Woods from the most debilitating aspects of his father’s master plan was that golfers cannot compete and achieve mega endorsements at the professional level until they have established credentials and grow into their adult bodies, when their stroke making becomes fully competitive and their product image ideal.

Therefore, a 6-year-old JonBenet Ramsey competing in beauty contests, or a 7-year-old Jessica Dubroff flying across country could have been Tiger, but they were not.

While awaiting his preordained career and endorsement deals, Tiger still needed to at least spend some time at college, in his case on a Stanford (Calif.) University golfing scholarship, while he accumulated U.S. amateur titles and fully established his credentials during this crucial time of normal development and “adolescent moratorium.”

According to the documentary,* being exposed to the “secret” extracurricular fringe benefits and sexual proclivities of golf pros with his father is likely to have been part of a traumatic “adultification” and compartmentalizing process. Whereby, one of Tiger’s roles became keeping his parents’ marriage together. That alleged exposure may also have planted the seeds for the “groupie” and sexual acting out challenges he so publicly experienced later in his career.

While Michael Jordan’s career has almost receded into the ancient and “hoary” past, Tiger Woods’s career at age 45, after overcoming significant back injuries and multiple failed surgeries, continues to astonish the golf and sporting world in general.

Most of his now deceased father Earl’s ambitions have indeed been realized despite some hiccups, setbacks, and loss of endorsements.

As parents in these challenging times, we all make sacrifices for our children, and in turn, expect them to step up to the plate and within reason, sacrifice and defer short-term excitement and fun for long-term educational, social, and life goals. How we as parents, and that includes Tiger Woods now, rise to this challenge is often a daily and humbling struggle.

While you watch this series, please keep your psychiatrist and family dynamics eyes wide open.
 

Dr. Tofler is a child and adolescent, sport psychiatrist, and is affiliated with Kaiser Permanente Psychiatry in West Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

References

1. Tofler IR et al. N Engl J Med. 1996 Jul 25;335(4):281-3.

2. Jellinek MS et al. J Am Acad Child Adolesc Psychiatry. 1999 Feb;38(2):213-6.

3. Tofler IR and DiGeronimo TF. “Keeping Your Kids Out Front Without Kicking Them From Behind: How to Nurture High-Achieving Athletes, Scholars, and Performing Artists.” (Hoboken, N.J,: Jossey-Bass, 2000).

4. Tofler IR et al. Clin Sports Med. 2005 Oct;24(4):805-28.

5. Clark TP et al. Clin Sports Med. 2005 Oct;24(4):959-71.

*Updated 1/25/2021

The Tiger Woods saga, which has been broadcast on HBO, is a “child” of the ESPN Michael Jordan series – which riveted early pandemic America. It is likely to exert a similar vicelike hold on the imagination of Biden transition/Trump impeachment II United States, despite not having the express participation of Woods himself.

The differences in parenting styles of these young African American men, at least superficially, appears in amazingly stark contrast.

Whereas Michael Jordan’s parents appear to have shown good old, red-blooded North Carolina ambitious and hard-driven tough parenting, Earl and Kultida Woods seem to have exerted a textbook example of what we call “achievement by proxy distortion” (ABPD) parenting style.^1-5

By deciding, even prior to birth, what their son’s future career would be, Earl, aided by Kultida Woods, created a master plan that came to fruition when Eldrick Tont “Tiger” Woods won his first Masters Tournament at the ripe old age of 21.

His parents’ fine-tuning of the ABPD template for professional sports parenting is often emulated. It had been earlier developed, in an industrial model – especially in women’s gymnastics – where Bela Karolyi and others in the Romanian Eastern Bloc system had developed Nadia Comaneci and others to be prepubescent superstars of the 1970s. When it was transferred to the more financially supportive, fertile base of the U.S., physical and sexual abuse were the acceptable price paid for Olympic gold medals.

When Tiger first appeared on the U.S. radar at the age of 2 on the Mike Douglas show in 1977, he was already definitively on the way to “prodigy” territory. Earl, a retired Vietnam veteran and product of the U.S. Marines, was able to model his own extraordinarily rigorous training where breaking down soldiers psychologically helps them survive special ops behind enemy lines. He trained his son essentially from birth, imprinting through somatic and postural echo these golf skills and habits for playing under pressure, handling annoying distraction, and self-hypnosis. These all clearly accelerated his son’s ability to enter the “zone,” a level of high attunement required, even demanded, at the highest levels of professional golf.

His parents’ ruthless approach, clearly accompanied by undoubted love and enthusiasm, to ending what appears to have been an age-appropriate high school relationship with his then “sweetheart,” appears on the surface a little cruel. But their approach achieved its purpose of sacrificing a distraction on the glorious golden path toward inevitable success and superstardom. This likely also produced a degree of self-objectification and further compartmentalization.

The typical outcome of ABPD is a fairly unidimensional identity defined by the activity, or in this case, the sport. In this case, where Earl was building or imagining a Messianic role for Tiger, multidimensionality was important as the self-described “Cablinasian” moniker suggests, whereby all of Tiger’s background of Caucasian, Black, Indian, and Asian ancestry was acknowledged as they all became lifelong fans.

What most likely saved Tiger Woods from the most debilitating aspects of his father’s master plan was that golfers cannot compete and achieve mega endorsements at the professional level until they have established credentials and grow into their adult bodies, when their stroke making becomes fully competitive and their product image ideal.

Therefore, a 6-year-old JonBenet Ramsey competing in beauty contests, or a 7-year-old Jessica Dubroff flying across country could have been Tiger, but they were not.

While awaiting his preordained career and endorsement deals, Tiger still needed to at least spend some time at college, in his case on a Stanford (Calif.) University golfing scholarship, while he accumulated U.S. amateur titles and fully established his credentials during this crucial time of normal development and “adolescent moratorium.”

According to the documentary,* being exposed to the “secret” extracurricular fringe benefits and sexual proclivities of golf pros with his father is likely to have been part of a traumatic “adultification” and compartmentalizing process. Whereby, one of Tiger’s roles became keeping his parents’ marriage together. That alleged exposure may also have planted the seeds for the “groupie” and sexual acting out challenges he so publicly experienced later in his career.

While Michael Jordan’s career has almost receded into the ancient and “hoary” past, Tiger Woods’s career at age 45, after overcoming significant back injuries and multiple failed surgeries, continues to astonish the golf and sporting world in general.

Most of his now deceased father Earl’s ambitions have indeed been realized despite some hiccups, setbacks, and loss of endorsements.

As parents in these challenging times, we all make sacrifices for our children, and in turn, expect them to step up to the plate and within reason, sacrifice and defer short-term excitement and fun for long-term educational, social, and life goals. How we as parents, and that includes Tiger Woods now, rise to this challenge is often a daily and humbling struggle.

While you watch this series, please keep your psychiatrist and family dynamics eyes wide open.
 

Dr. Tofler is a child and adolescent, sport psychiatrist, and is affiliated with Kaiser Permanente Psychiatry in West Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

References

1. Tofler IR et al. N Engl J Med. 1996 Jul 25;335(4):281-3.

2. Jellinek MS et al. J Am Acad Child Adolesc Psychiatry. 1999 Feb;38(2):213-6.

3. Tofler IR and DiGeronimo TF. “Keeping Your Kids Out Front Without Kicking Them From Behind: How to Nurture High-Achieving Athletes, Scholars, and Performing Artists.” (Hoboken, N.J,: Jossey-Bass, 2000).

4. Tofler IR et al. Clin Sports Med. 2005 Oct;24(4):805-28.

5. Clark TP et al. Clin Sports Med. 2005 Oct;24(4):959-71.

*Updated 1/25/2021

The Tiger Woods saga, which has been broadcast on HBO, is a “child” of the ESPN Michael Jordan series – which riveted early pandemic America. It is likely to exert a similar vicelike hold on the imagination of Biden transition/Trump impeachment II United States, despite not having the express participation of Woods himself.

The differences in parenting styles of these young African American men, at least superficially, appears in amazingly stark contrast.

Whereas Michael Jordan’s parents appear to have shown good old, red-blooded North Carolina ambitious and hard-driven tough parenting, Earl and Kultida Woods seem to have exerted a textbook example of what we call “achievement by proxy distortion” (ABPD) parenting style.^1-5

By deciding, even prior to birth, what their son’s future career would be, Earl, aided by Kultida Woods, created a master plan that came to fruition when Eldrick Tont “Tiger” Woods won his first Masters Tournament at the ripe old age of 21.

His parents’ fine-tuning of the ABPD template for professional sports parenting is often emulated. It had been earlier developed, in an industrial model – especially in women’s gymnastics – where Bela Karolyi and others in the Romanian Eastern Bloc system had developed Nadia Comaneci and others to be prepubescent superstars of the 1970s. When it was transferred to the more financially supportive, fertile base of the U.S., physical and sexual abuse were the acceptable price paid for Olympic gold medals.

When Tiger first appeared on the U.S. radar at the age of 2 on the Mike Douglas show in 1977, he was already definitively on the way to “prodigy” territory. Earl, a retired Vietnam veteran and product of the U.S. Marines, was able to model his own extraordinarily rigorous training where breaking down soldiers psychologically helps them survive special ops behind enemy lines. He trained his son essentially from birth, imprinting through somatic and postural echo these golf skills and habits for playing under pressure, handling annoying distraction, and self-hypnosis. These all clearly accelerated his son’s ability to enter the “zone,” a level of high attunement required, even demanded, at the highest levels of professional golf.

His parents’ ruthless approach, clearly accompanied by undoubted love and enthusiasm, to ending what appears to have been an age-appropriate high school relationship with his then “sweetheart,” appears on the surface a little cruel. But their approach achieved its purpose of sacrificing a distraction on the glorious golden path toward inevitable success and superstardom. This likely also produced a degree of self-objectification and further compartmentalization.

The typical outcome of ABPD is a fairly unidimensional identity defined by the activity, or in this case, the sport. In this case, where Earl was building or imagining a Messianic role for Tiger, multidimensionality was important as the self-described “Cablinasian” moniker suggests, whereby all of Tiger’s background of Caucasian, Black, Indian, and Asian ancestry was acknowledged as they all became lifelong fans.

What most likely saved Tiger Woods from the most debilitating aspects of his father’s master plan was that golfers cannot compete and achieve mega endorsements at the professional level until they have established credentials and grow into their adult bodies, when their stroke making becomes fully competitive and their product image ideal.

Therefore, a 6-year-old JonBenet Ramsey competing in beauty contests, or a 7-year-old Jessica Dubroff flying across country could have been Tiger, but they were not.

While awaiting his preordained career and endorsement deals, Tiger still needed to at least spend some time at college, in his case on a Stanford (Calif.) University golfing scholarship, while he accumulated U.S. amateur titles and fully established his credentials during this crucial time of normal development and “adolescent moratorium.”

According to the documentary,* being exposed to the “secret” extracurricular fringe benefits and sexual proclivities of golf pros with his father is likely to have been part of a traumatic “adultification” and compartmentalizing process. Whereby, one of Tiger’s roles became keeping his parents’ marriage together. That alleged exposure may also have planted the seeds for the “groupie” and sexual acting out challenges he so publicly experienced later in his career.

While Michael Jordan’s career has almost receded into the ancient and “hoary” past, Tiger Woods’s career at age 45, after overcoming significant back injuries and multiple failed surgeries, continues to astonish the golf and sporting world in general.

Most of his now deceased father Earl’s ambitions have indeed been realized despite some hiccups, setbacks, and loss of endorsements.

As parents in these challenging times, we all make sacrifices for our children, and in turn, expect them to step up to the plate and within reason, sacrifice and defer short-term excitement and fun for long-term educational, social, and life goals. How we as parents, and that includes Tiger Woods now, rise to this challenge is often a daily and humbling struggle.

While you watch this series, please keep your psychiatrist and family dynamics eyes wide open.
 

Dr. Tofler is a child and adolescent, sport psychiatrist, and is affiliated with Kaiser Permanente Psychiatry in West Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.

References

1. Tofler IR et al. N Engl J Med. 1996 Jul 25;335(4):281-3.

2. Jellinek MS et al. J Am Acad Child Adolesc Psychiatry. 1999 Feb;38(2):213-6.

3. Tofler IR and DiGeronimo TF. “Keeping Your Kids Out Front Without Kicking Them From Behind: How to Nurture High-Achieving Athletes, Scholars, and Performing Artists.” (Hoboken, N.J,: Jossey-Bass, 2000).

4. Tofler IR et al. Clin Sports Med. 2005 Oct;24(4):805-28.

5. Clark TP et al. Clin Sports Med. 2005 Oct;24(4):959-71.

*Updated 1/25/2021

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Childhood treatment with recombinant human growth hormone was associated with a significantly increased risk of cardiovascular events, based on data from more than 3,000 individuals.

“Both excess levels of growth hormone and [growth hormone deficiency] have been associated with increased cardiovascular morbidity and mortality,” but data on long-term cardiovascular morbidity in individuals treated with growth hormone in childhood are lacking, wrote Anders Tinblad, MD, of Karolinska Institutet, Stockholm, and colleagues.

In a population-based cohort study published in JAMA Pediatrics, the researchers identified 3,408 Swedish patients treated as children with recombinant human growth hormone (rhGH) between Jan. 1, 1985, and Dec. 31, 2010, and compared each with 15 matched controls (a total of 50,036 controls). The patients were treated for one of three conditions: isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS).

Data on cardiovascular outcomes were collected from health care and population-based registers and analyzed between Jan. 1, 1985, and Dec. 31, 2014. The average age of the participants at the study’s end was 25.1 years.

In all, 1,809 cardiovascular disease events were recorded over a median follow-up period of 14.9 years, for an incidence rate of 25.6 events per 10,000 person-years in patients and 22.6 events per 10,000 person-years in controls.

When separated by sex, the incidence was higher in female patients compared with controls (31.2 vs. 23.4 events per 10,000 person-years, respectively, but similar in male patients vs. controls (23.3 vs. 22.3 events per 10,000 person-years). “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this sex difference still remains unclear and merits further investigation,” the researchers wrote.

Overall, the highest adjusted hazard ratios occurred in subgroups of patients with the longest treatment duration (HR 2.08) and highest cumulative dose of growth hormone (HR 2.05), but no association was noted between highest daily hormone dose and cardiovascular event risk. Hazard ratios were higher across all three treatment subgroups of SGA, GHD, and ISS compared with controls (HR 1.97, 1.66, and 1.55, respectively).

“The association between childhood rhGH treatment and CVD events was also seen when assessing only severe CVD outcomes, but with even lower absolute risks,” the researchers noted.

The study findings were limited by several factors including the potential for confounding by treatment indication and the lack of long-term follow-up data given the relatively young age of the study population, the researchers said. The results were strengthened by the large sample size and showed that the absolute risk for overall and severe cardiovascular disease in children treated with growth hormones was low, “which could be reassuring to individual patients,” they added. However, “At the group level, and perhaps especially for female patients and those treated for SGA indication, further close monitoring and future studies of CVD safety are warranted,” they concluded.
 

Safety and ethical concerns persist

Although the study authors cite limited conclusions on causality and low absolute risk, several issues persist that prompt ongoing analysis of pediatric growth hormone use, namely “worrisome indirect evidence, challenges and limitations in the direct evidence, and the changing world of growth hormone treatment,” Adda Grimberg, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

“Although evidence asserts that neither growth hormone nor insulinlike growth factor I is carcinogenic, the basic science and oncology literatures are rife with reports showing that they can make aberrant cells more aggressive,” and such indirect evidence supports the need for more direct evidence of possible harm from growth hormone treatment, Dr. Grimberg wrote. Most current safety data on growth hormone come from postmarketing surveillance studies, but these studies do not include controls or data on outcomes after discontinuation of treatment, she noted.

The current study, while able to follow patients across the lifespan, cannot indicate “whether the small but increased risk of cardiovascular disease found in this study was caused by the pediatric growth hormone treatment that identified the participants, by the conditions being treated, by other potential confounder(s) not captured by the study’s methods, or by a combination of the above,” said Dr. Grimberg.

In addition, “the move from replacement of GHD to pharmacologic height augmentation in children who already make sufficient growth hormone had the potential to change the safety profile of treatment,” she said.

“Parents of patients in pediatric primary care practices and of patients seeking growth-related care in a subspecialty endocrine clinic rated treatment characteristics (i.e., proven efficacy and safety) as the factor most having a big or extreme effect on their growth-related medical decision-making,” Dr. Grimberg said. “The centrality of treatment safety to patient-family decision-making underscores the importance of continued scrutiny of growth hormone safety as the treatment and its recipients continue to evolve,” she concluded.

The study was supported by the Swedish Research Council, the Stockholm City Council, the Karolinska Institute, the Society for Child Care, Sahlgrenska University Hospital, and the Stockholm County Council’s combined clinical residency and PhD training program. Lead author Dr. Tidblad disclosed funding from the Society for Child Care and Stockholm County Council during the conduct of the study and personal fees from Pfizer. Dr. Grimberg disclosed serving as a member of the steering committee for the Pfizer International Growth Study Database, and as a consultant for the Pediatric Endocrine Society GH Deficiency Knowledge Center, sponsored by Sandoz AG.

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

The list of things to be ungrateful for last year is long. You’re not supposed to make this list, though. The best practice is to list what you’re grateful for, even when living in trying times. That’s a long list too, but I find making it similarly unfruitful.

Of course, I’m grateful I don’t have COVID-19, thankful my practice hasn’t been significantly impacted, grateful I got the vaccine. But simply repeating these gratitudes daily seems ineffective. I’ve learned a different “gratefulness practice” that perhaps works better.

AscentXmedia/E+

The last question is the best. We all spend time thinking about what others think of us. We should spend time thinking about what impact we’ve had on them. Like a cold shower, it’s both briskly awakening and easy to do. Go back through your day and reflect on what you did that made things difficult for others. It can be as simple as I started whining about how a patient waylaid me with her silly complaints. That led to my colleague’s joining in about difficult patients. Or I was late turning in my article, which made my editor have to work harder to get it completed in time.

There’s plenty of things we should be grateful for. In doing these exercises you’ll learn just how much others have cared for you and, I hope, how you might do things to make them grateful for you.

If you’re interested in learning more about Naikan, I discovered this from Brett McKay’s The Art of Manliness podcast and the teaching of Gregg Krech, summarized in his book, “Naikan: Gratitude, Grace, and the Japanese Art of Self-Reflection.”
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com .

The list of things to be ungrateful for last year is long. You’re not supposed to make this list, though. The best practice is to list what you’re grateful for, even when living in trying times. That’s a long list too, but I find making it similarly unfruitful.

Of course, I’m grateful I don’t have COVID-19, thankful my practice hasn’t been significantly impacted, grateful I got the vaccine. But simply repeating these gratitudes daily seems ineffective. I’ve learned a different “gratefulness practice” that perhaps works better.

AscentXmedia/E+

The last question is the best. We all spend time thinking about what others think of us. We should spend time thinking about what impact we’ve had on them. Like a cold shower, it’s both briskly awakening and easy to do. Go back through your day and reflect on what you did that made things difficult for others. It can be as simple as I started whining about how a patient waylaid me with her silly complaints. That led to my colleague’s joining in about difficult patients. Or I was late turning in my article, which made my editor have to work harder to get it completed in time.

There’s plenty of things we should be grateful for. In doing these exercises you’ll learn just how much others have cared for you and, I hope, how you might do things to make them grateful for you.

If you’re interested in learning more about Naikan, I discovered this from Brett McKay’s The Art of Manliness podcast and the teaching of Gregg Krech, summarized in his book, “Naikan: Gratitude, Grace, and the Japanese Art of Self-Reflection.”
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com .

The list of things to be ungrateful for last year is long. You’re not supposed to make this list, though. The best practice is to list what you’re grateful for, even when living in trying times. That’s a long list too, but I find making it similarly unfruitful.

Of course, I’m grateful I don’t have COVID-19, thankful my practice hasn’t been significantly impacted, grateful I got the vaccine. But simply repeating these gratitudes daily seems ineffective. I’ve learned a different “gratefulness practice” that perhaps works better.

AscentXmedia/E+

The last question is the best. We all spend time thinking about what others think of us. We should spend time thinking about what impact we’ve had on them. Like a cold shower, it’s both briskly awakening and easy to do. Go back through your day and reflect on what you did that made things difficult for others. It can be as simple as I started whining about how a patient waylaid me with her silly complaints. That led to my colleague’s joining in about difficult patients. Or I was late turning in my article, which made my editor have to work harder to get it completed in time.

There’s plenty of things we should be grateful for. In doing these exercises you’ll learn just how much others have cared for you and, I hope, how you might do things to make them grateful for you.

If you’re interested in learning more about Naikan, I discovered this from Brett McKay’s The Art of Manliness podcast and the teaching of Gregg Krech, summarized in his book, “Naikan: Gratitude, Grace, and the Japanese Art of Self-Reflection.”
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com .

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Nipple eczema is a dermatitis of the nipple and areola with clinical features such as erythema, fissures, scaling, pruritus, and crusting.^1,2 It is classically associated with atopic dermatitis (AD), though it may occur as an isolated condition less commonly. While it may affect female adolescents, nipple eczema has also been reported in boys and breastfeeding women.^3,4 The overall risk of incidence of nipple dermatitis has also been shown to increase with age.⁵ Nipple eczema is considered a cutaneous finding of AD, and is listed as a minor diagnostic criteria for AD in the Hanifin-Rajka criteria.⁶ The patient had not related his history of AD, which was elicited after finding typical antecubital eczematous dermatitis, and he had not been actively treating it.
 

Diagnosis and differential

Nipple eczema may be a challenging diagnosis for various reasons. For example, a unilateral presentation and the changes in the eczematous lesions overlying the nipple and areola’s varying textures and colors can make it difficult for clinicians to identify.³ Many children and adolescents, including our patient, are initially diagnosed as having impetigo and treated with antibiotics. The diagnosis of nipple eczema is made clinically, and management straightforward (see below). However, additional testing may be appropriate including patch testing for allergic contact dermatitis or bacterial cultures if bacterial infection or superinfection is considered.^7,8 The differential diagnosis for nipple eczema includes impetigo, gynecomastia, scabies, and allergic contact dermatitis.

Impetigo typically presents with honey-colored crusts or pustules caused by infection with Staphylococcus aureus or Streptococcus. Patients with AD have higher rates of colonization with S. aureus and impetiginized eczema in common. Impetigo of the nipple and areola is more common in breastfeeding women as skin cracking from lactation can lead to exposure to bacteria from the infant’s mouth.⁹ Treatments involve topical or oral antibiotics.

Gynecomastia is the development of male breast tissue with most cases hypothesized to be caused by an imbalance between androgens and estrogens.¹⁰ Some other causes include direct skin contact with topical estrogen sprays and recreational use of marijuana and heroin.¹¹ It is usually a benign exam finding in adolescent boys. However, clinical findings such as overlying skin changes, rapidly enlarging masses, and constitutional symptoms are concerning in the setting of gynecomastia and warrant further evaluation.

Scabies, which is caused by the infestation of scabies mites, is a common infectious skin disease. The classic presentation includes a rash that is intensely itchy, especially at night. Crusted scabies of the nipples may be difficult to distinguish from nipple eczema. Areas of frequent involvement of scabies include palms, between fingers, armpits, groin, between toes, and feet. Treatments include treating all household members with permethrin cream and washing all clothes and bedding in contact with a scabies-infected patient in high heat, or oral ivermectin in certain circumstances.¹²

Allergic contact dermatitis is a common cause of breast and nipple dermatitis and should be considered within the differential diagnosis of nipple eczema with atopic dermatitis, or as an exacerbator.^7,9 Patients in particular who present with bilateral involvement extending to the periareolar skin, or unusual bilateral focal patterns suggestive for contact allergy should be considered for allergic contact dermatitis evaluation with patch tests. A common causative agent for allergic contact dermatitis of the breast and nipple includes Cl+Me-isothiazolinone, commonly found in detergents and fabric softeners.⁷ Primary treatment includes avoidance of the offending agents.
 

Treatment

Topical corticosteroids are first-line treatment for treating nipple eczema. Low-potency topical steroids can be used for maintenance and mild eczema while more potent steroids are useful for more severe cases. In addition to topical medication therapy, frequent emollient use to protect the skin barrier and the elimination of any irritants are essential to a successful treatment course. Unilateral nipple eczema can also be secondary to inadequate treatment of AD, demonstrating the importance of addressing the underlying AD with therapy.³

Our patient was diagnosed with nipple eczema based on clinical presentation of an eczematous left nipple in the setting of active atopic dermatitis and minimal improvement on topical antibiotic. He was started on a 3-week course of fluocinonide 0.05% topical ointment (a potent topical corticosteroid) twice daily for 2 weeks with plans to transition to triamcinolone 0.1% topical ointment several times a week.

Ms. Park is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Neither Ms. Park nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Pediatr Dermatol. 2005;22(1):64-6.

2. Am J Dermatopathol. 2015;37(4):284-8.

3. Pediatr Dermatol. 2015;32(5):718-22.

4. J Cutan Med Surg. 2004;8(2):126-30.

5. Pediatr Dermatol. 2012;29(5):580-3.

6. Dermatologica. 1988;177(6):360-4.

7. Ann Dermatol. 2014;26(3):413-4.

8. BMJ Case Rep. 2020;13(8).

9. J Am Acad Dermatol. 2019;80(6):1483-94.

10. Pediatr Endocrinol Rev. 2017;14(4):371-7.

11. JAMA. 2010;304(9):953.

12. JAMA. 2018;320(6):612.

Nipple eczema is a dermatitis of the nipple and areola with clinical features such as erythema, fissures, scaling, pruritus, and crusting.^1,2 It is classically associated with atopic dermatitis (AD), though it may occur as an isolated condition less commonly. While it may affect female adolescents, nipple eczema has also been reported in boys and breastfeeding women.^3,4 The overall risk of incidence of nipple dermatitis has also been shown to increase with age.⁵ Nipple eczema is considered a cutaneous finding of AD, and is listed as a minor diagnostic criteria for AD in the Hanifin-Rajka criteria.⁶ The patient had not related his history of AD, which was elicited after finding typical antecubital eczematous dermatitis, and he had not been actively treating it.
 

Diagnosis and differential

Nipple eczema may be a challenging diagnosis for various reasons. For example, a unilateral presentation and the changes in the eczematous lesions overlying the nipple and areola’s varying textures and colors can make it difficult for clinicians to identify.³ Many children and adolescents, including our patient, are initially diagnosed as having impetigo and treated with antibiotics. The diagnosis of nipple eczema is made clinically, and management straightforward (see below). However, additional testing may be appropriate including patch testing for allergic contact dermatitis or bacterial cultures if bacterial infection or superinfection is considered.^7,8 The differential diagnosis for nipple eczema includes impetigo, gynecomastia, scabies, and allergic contact dermatitis.

Impetigo typically presents with honey-colored crusts or pustules caused by infection with Staphylococcus aureus or Streptococcus. Patients with AD have higher rates of colonization with S. aureus and impetiginized eczema in common. Impetigo of the nipple and areola is more common in breastfeeding women as skin cracking from lactation can lead to exposure to bacteria from the infant’s mouth.⁹ Treatments involve topical or oral antibiotics.

Gynecomastia is the development of male breast tissue with most cases hypothesized to be caused by an imbalance between androgens and estrogens.¹⁰ Some other causes include direct skin contact with topical estrogen sprays and recreational use of marijuana and heroin.¹¹ It is usually a benign exam finding in adolescent boys. However, clinical findings such as overlying skin changes, rapidly enlarging masses, and constitutional symptoms are concerning in the setting of gynecomastia and warrant further evaluation.

Scabies, which is caused by the infestation of scabies mites, is a common infectious skin disease. The classic presentation includes a rash that is intensely itchy, especially at night. Crusted scabies of the nipples may be difficult to distinguish from nipple eczema. Areas of frequent involvement of scabies include palms, between fingers, armpits, groin, between toes, and feet. Treatments include treating all household members with permethrin cream and washing all clothes and bedding in contact with a scabies-infected patient in high heat, or oral ivermectin in certain circumstances.¹²

Allergic contact dermatitis is a common cause of breast and nipple dermatitis and should be considered within the differential diagnosis of nipple eczema with atopic dermatitis, or as an exacerbator.^7,9 Patients in particular who present with bilateral involvement extending to the periareolar skin, or unusual bilateral focal patterns suggestive for contact allergy should be considered for allergic contact dermatitis evaluation with patch tests. A common causative agent for allergic contact dermatitis of the breast and nipple includes Cl+Me-isothiazolinone, commonly found in detergents and fabric softeners.⁷ Primary treatment includes avoidance of the offending agents.
 

Treatment

Topical corticosteroids are first-line treatment for treating nipple eczema. Low-potency topical steroids can be used for maintenance and mild eczema while more potent steroids are useful for more severe cases. In addition to topical medication therapy, frequent emollient use to protect the skin barrier and the elimination of any irritants are essential to a successful treatment course. Unilateral nipple eczema can also be secondary to inadequate treatment of AD, demonstrating the importance of addressing the underlying AD with therapy.³

Our patient was diagnosed with nipple eczema based on clinical presentation of an eczematous left nipple in the setting of active atopic dermatitis and minimal improvement on topical antibiotic. He was started on a 3-week course of fluocinonide 0.05% topical ointment (a potent topical corticosteroid) twice daily for 2 weeks with plans to transition to triamcinolone 0.1% topical ointment several times a week.

Ms. Park is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Neither Ms. Park nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Pediatr Dermatol. 2005;22(1):64-6.

2. Am J Dermatopathol. 2015;37(4):284-8.

3. Pediatr Dermatol. 2015;32(5):718-22.

4. J Cutan Med Surg. 2004;8(2):126-30.

5. Pediatr Dermatol. 2012;29(5):580-3.

6. Dermatologica. 1988;177(6):360-4.

7. Ann Dermatol. 2014;26(3):413-4.

8. BMJ Case Rep. 2020;13(8).

9. J Am Acad Dermatol. 2019;80(6):1483-94.

10. Pediatr Endocrinol Rev. 2017;14(4):371-7.

11. JAMA. 2010;304(9):953.

12. JAMA. 2018;320(6):612.

Nipple eczema is a dermatitis of the nipple and areola with clinical features such as erythema, fissures, scaling, pruritus, and crusting.^1,2 It is classically associated with atopic dermatitis (AD), though it may occur as an isolated condition less commonly. While it may affect female adolescents, nipple eczema has also been reported in boys and breastfeeding women.^3,4 The overall risk of incidence of nipple dermatitis has also been shown to increase with age.⁵ Nipple eczema is considered a cutaneous finding of AD, and is listed as a minor diagnostic criteria for AD in the Hanifin-Rajka criteria.⁶ The patient had not related his history of AD, which was elicited after finding typical antecubital eczematous dermatitis, and he had not been actively treating it.
 

Diagnosis and differential

Nipple eczema may be a challenging diagnosis for various reasons. For example, a unilateral presentation and the changes in the eczematous lesions overlying the nipple and areola’s varying textures and colors can make it difficult for clinicians to identify.³ Many children and adolescents, including our patient, are initially diagnosed as having impetigo and treated with antibiotics. The diagnosis of nipple eczema is made clinically, and management straightforward (see below). However, additional testing may be appropriate including patch testing for allergic contact dermatitis or bacterial cultures if bacterial infection or superinfection is considered.^7,8 The differential diagnosis for nipple eczema includes impetigo, gynecomastia, scabies, and allergic contact dermatitis.

Impetigo typically presents with honey-colored crusts or pustules caused by infection with Staphylococcus aureus or Streptococcus. Patients with AD have higher rates of colonization with S. aureus and impetiginized eczema in common. Impetigo of the nipple and areola is more common in breastfeeding women as skin cracking from lactation can lead to exposure to bacteria from the infant’s mouth.⁹ Treatments involve topical or oral antibiotics.

Gynecomastia is the development of male breast tissue with most cases hypothesized to be caused by an imbalance between androgens and estrogens.¹⁰ Some other causes include direct skin contact with topical estrogen sprays and recreational use of marijuana and heroin.¹¹ It is usually a benign exam finding in adolescent boys. However, clinical findings such as overlying skin changes, rapidly enlarging masses, and constitutional symptoms are concerning in the setting of gynecomastia and warrant further evaluation.

Scabies, which is caused by the infestation of scabies mites, is a common infectious skin disease. The classic presentation includes a rash that is intensely itchy, especially at night. Crusted scabies of the nipples may be difficult to distinguish from nipple eczema. Areas of frequent involvement of scabies include palms, between fingers, armpits, groin, between toes, and feet. Treatments include treating all household members with permethrin cream and washing all clothes and bedding in contact with a scabies-infected patient in high heat, or oral ivermectin in certain circumstances.¹²

Allergic contact dermatitis is a common cause of breast and nipple dermatitis and should be considered within the differential diagnosis of nipple eczema with atopic dermatitis, or as an exacerbator.^7,9 Patients in particular who present with bilateral involvement extending to the periareolar skin, or unusual bilateral focal patterns suggestive for contact allergy should be considered for allergic contact dermatitis evaluation with patch tests. A common causative agent for allergic contact dermatitis of the breast and nipple includes Cl+Me-isothiazolinone, commonly found in detergents and fabric softeners.⁷ Primary treatment includes avoidance of the offending agents.
 

Treatment

Topical corticosteroids are first-line treatment for treating nipple eczema. Low-potency topical steroids can be used for maintenance and mild eczema while more potent steroids are useful for more severe cases. In addition to topical medication therapy, frequent emollient use to protect the skin barrier and the elimination of any irritants are essential to a successful treatment course. Unilateral nipple eczema can also be secondary to inadequate treatment of AD, demonstrating the importance of addressing the underlying AD with therapy.³

Our patient was diagnosed with nipple eczema based on clinical presentation of an eczematous left nipple in the setting of active atopic dermatitis and minimal improvement on topical antibiotic. He was started on a 3-week course of fluocinonide 0.05% topical ointment (a potent topical corticosteroid) twice daily for 2 weeks with plans to transition to triamcinolone 0.1% topical ointment several times a week.

Ms. Park is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Neither Ms. Park nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Pediatr Dermatol. 2005;22(1):64-6.

2. Am J Dermatopathol. 2015;37(4):284-8.

3. Pediatr Dermatol. 2015;32(5):718-22.

4. J Cutan Med Surg. 2004;8(2):126-30.

5. Pediatr Dermatol. 2012;29(5):580-3.

6. Dermatologica. 1988;177(6):360-4.

7. Ann Dermatol. 2014;26(3):413-4.

8. BMJ Case Rep. 2020;13(8).

9. J Am Acad Dermatol. 2019;80(6):1483-94.

10. Pediatr Endocrinol Rev. 2017;14(4):371-7.

11. JAMA. 2010;304(9):953.

12. JAMA. 2018;320(6):612.

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

Do you accept new families into your practice who have already chosen to not have their children immunized? What about families who have been in your practice for several months or years? In 2016 the American Academy of Pediatrics published a clinical report in which it stated that, under some circumstances, dismissing families who refuse to vaccinate is permissible. Have you felt sufficiently supported by that statement and dismissed any families after multiple attempts at education on your part?

In a Pediatrics Perspective article in the December issue of Pediatrics, two philosophers and a physician make the argument that, while in some situations dismissing a family who refuses vaccines may be “an ethically acceptable option” refusing to accept a family with the same philosophy is not. It is an interesting paper and worth reading regardless of whether or not you already accept and continue to tolerate vaccine deniers in your practice.

The Pediatrics Perspective is certainly not the last word on the ethics of caring for families who deny their children care that we believe is critical to their health and the welfare of the community at large. There has been a lot of discussion about the issue but little has been written about how we as the physicians on the front line are coping emotionally with what the authors of the paper call the “burdens associated with treating” families who refuse to follow our guidance.

It is hard not to feel angry when a family you have invested valuable office time in discussing the benefits and safety of vaccines continues to disregard what you see as the facts. The time you have spent with them is not just income-generating time for your practice, it is time stolen from other families who are more willing to follow your recommendations. In how many visits will you continue to raise the issue? Unless I saw a glimmer of hope I would usually stop after two wasted encounters. But, the issue would still linger as the elephant in the examination room for as long as I continued to see the patient.

How have you expressed your anger? Have you been argumentative or rude? You may have been able maintain your composure and remain civil and appear caring, but I suspect the anger is still gnawing at you. And, there is still the frustration and feeling of impotence. You may have questioned your ability as an educator. You should get over that notion quickly. There is ample evidence that most vaccine deniers are not going to be convinced by even the most carefully presented information. I suggest you leave it to others to try their hands at education. Let them invest their time while you tend to the needs of your other patients. You can try being a fear monger and, while fear can be effective, you have better ways to spend your office day than telling horror stories.

If vaccine denial makes you feel powerless, you should get over that pretty quickly as well and accept the fact that you are simply an advisor. If you believe that most of the families in your practice are following your recommendations as though you had presented them on stone tablets, it is time for a wakeup call.

Finally, there is the most troubling emotion associated with vaccine refusal and that is fear, the fear of being sued. Establishing a relationship with a family is one that requires mutual trust and certainly vaccine refusal will put that trust in question, particularly if you have done a less than adequate job of hiding your anger and frustration with their unfortunate decision.

For now, vaccine refusal is just another one of those crosses that those of us in primary care must bear together wearing the best face we can put forward. That doesn’t mean we can’t share those emotions with our peers. Misery does love company.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Do you accept new families into your practice who have already chosen to not have their children immunized? What about families who have been in your practice for several months or years? In 2016 the American Academy of Pediatrics published a clinical report in which it stated that, under some circumstances, dismissing families who refuse to vaccinate is permissible. Have you felt sufficiently supported by that statement and dismissed any families after multiple attempts at education on your part?

In a Pediatrics Perspective article in the December issue of Pediatrics, two philosophers and a physician make the argument that, while in some situations dismissing a family who refuses vaccines may be “an ethically acceptable option” refusing to accept a family with the same philosophy is not. It is an interesting paper and worth reading regardless of whether or not you already accept and continue to tolerate vaccine deniers in your practice.

The Pediatrics Perspective is certainly not the last word on the ethics of caring for families who deny their children care that we believe is critical to their health and the welfare of the community at large. There has been a lot of discussion about the issue but little has been written about how we as the physicians on the front line are coping emotionally with what the authors of the paper call the “burdens associated with treating” families who refuse to follow our guidance.

It is hard not to feel angry when a family you have invested valuable office time in discussing the benefits and safety of vaccines continues to disregard what you see as the facts. The time you have spent with them is not just income-generating time for your practice, it is time stolen from other families who are more willing to follow your recommendations. In how many visits will you continue to raise the issue? Unless I saw a glimmer of hope I would usually stop after two wasted encounters. But, the issue would still linger as the elephant in the examination room for as long as I continued to see the patient.

How have you expressed your anger? Have you been argumentative or rude? You may have been able maintain your composure and remain civil and appear caring, but I suspect the anger is still gnawing at you. And, there is still the frustration and feeling of impotence. You may have questioned your ability as an educator. You should get over that notion quickly. There is ample evidence that most vaccine deniers are not going to be convinced by even the most carefully presented information. I suggest you leave it to others to try their hands at education. Let them invest their time while you tend to the needs of your other patients. You can try being a fear monger and, while fear can be effective, you have better ways to spend your office day than telling horror stories.

If vaccine denial makes you feel powerless, you should get over that pretty quickly as well and accept the fact that you are simply an advisor. If you believe that most of the families in your practice are following your recommendations as though you had presented them on stone tablets, it is time for a wakeup call.

Finally, there is the most troubling emotion associated with vaccine refusal and that is fear, the fear of being sued. Establishing a relationship with a family is one that requires mutual trust and certainly vaccine refusal will put that trust in question, particularly if you have done a less than adequate job of hiding your anger and frustration with their unfortunate decision.

For now, vaccine refusal is just another one of those crosses that those of us in primary care must bear together wearing the best face we can put forward. That doesn’t mean we can’t share those emotions with our peers. Misery does love company.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Do you accept new families into your practice who have already chosen to not have their children immunized? What about families who have been in your practice for several months or years? In 2016 the American Academy of Pediatrics published a clinical report in which it stated that, under some circumstances, dismissing families who refuse to vaccinate is permissible. Have you felt sufficiently supported by that statement and dismissed any families after multiple attempts at education on your part?

In a Pediatrics Perspective article in the December issue of Pediatrics, two philosophers and a physician make the argument that, while in some situations dismissing a family who refuses vaccines may be “an ethically acceptable option” refusing to accept a family with the same philosophy is not. It is an interesting paper and worth reading regardless of whether or not you already accept and continue to tolerate vaccine deniers in your practice.

The Pediatrics Perspective is certainly not the last word on the ethics of caring for families who deny their children care that we believe is critical to their health and the welfare of the community at large. There has been a lot of discussion about the issue but little has been written about how we as the physicians on the front line are coping emotionally with what the authors of the paper call the “burdens associated with treating” families who refuse to follow our guidance.

It is hard not to feel angry when a family you have invested valuable office time in discussing the benefits and safety of vaccines continues to disregard what you see as the facts. The time you have spent with them is not just income-generating time for your practice, it is time stolen from other families who are more willing to follow your recommendations. In how many visits will you continue to raise the issue? Unless I saw a glimmer of hope I would usually stop after two wasted encounters. But, the issue would still linger as the elephant in the examination room for as long as I continued to see the patient.

How have you expressed your anger? Have you been argumentative or rude? You may have been able maintain your composure and remain civil and appear caring, but I suspect the anger is still gnawing at you. And, there is still the frustration and feeling of impotence. You may have questioned your ability as an educator. You should get over that notion quickly. There is ample evidence that most vaccine deniers are not going to be convinced by even the most carefully presented information. I suggest you leave it to others to try their hands at education. Let them invest their time while you tend to the needs of your other patients. You can try being a fear monger and, while fear can be effective, you have better ways to spend your office day than telling horror stories.

If vaccine denial makes you feel powerless, you should get over that pretty quickly as well and accept the fact that you are simply an advisor. If you believe that most of the families in your practice are following your recommendations as though you had presented them on stone tablets, it is time for a wakeup call.

Finally, there is the most troubling emotion associated with vaccine refusal and that is fear, the fear of being sued. Establishing a relationship with a family is one that requires mutual trust and certainly vaccine refusal will put that trust in question, particularly if you have done a less than adequate job of hiding your anger and frustration with their unfortunate decision.

For now, vaccine refusal is just another one of those crosses that those of us in primary care must bear together wearing the best face we can put forward. That doesn’t mean we can’t share those emotions with our peers. Misery does love company.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Outpatient management of most afebrile infants with acute otitis media who haven’t been tested for invasive bacterial infection may be reasonable given the low occurrence of adverse events, said Son H. McLaren, MD, MS, of Columbia University, New York, and colleagues.

Dr. McLaren and associates conducted an international cross-sectional study at 33 emergency departments participating in the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics (AAP): 29 in the United States, 2 in Canada and 2 in Spain.

The researchers sought first to assess prevalence of invasive bacterial infections and adverse events tied to acute otitis media (AOM) in infants 90 days and younger. Those who were clinically diagnosed with AOM and presented without fever between January 2007 and December 2017 were included in the study. The presence of fever, they explained, “is a primary driver for more expanded testing and/or empirical treatment of invasive bacterial infection (IBI). Secondarily, they sought to characterize patterns of diagnostic testing and the factors associated with it specifically in this patient population.

Of 5,270 patients screened, 1,637 met study criteria. Included patients were a median age of 68 days. A total of 1,459 (89.1%) met AAP diagnostic criteria for AOM. The remaining 178 patients were examined and found to have more than one of these criteria: 113 had opacification of tympanic membrane, 57 had dull tympanic membrane, 25 had decreased visualization of middle ear structures, 9 had middle ear effusion, 8 had visible tympanic membrane perforation and 5 had decreased tympanic membrane mobility with insufflation. None of the 278 infants with blood cultures had bacteremia, nor were they diagnosed with bacterial meningitis. Two of 645 (0.3%) infants experienced adverse events, as evidenced with 30-day follow-up or history of hospitalization.

Dr. McLaren and colleagues observed that despite a low prevalence of IBI and AOM-associated adverse events, more than one-fifth of patients were prescribed diagnostic testing for IBI and subsequently hospitalized, a practice that appeared more common with younger patients.
 

Significant testing and hospitalizations persisted despite low prevalence of IBIs

Although diagnostic testing and hospitalizations differed by site, they were, in fact, “substantial in contrast to the low prevalence of IBIs and adverse events,” the researchers noted. “Our data may be used to help guide clinical management of afebrile infants with clinician-diagnosed AOM, who are not included in the current AAP AOM practice guideline,” the authors said. They speculated that this practice may be due, in part, to young-age risk of IBI and the concern for IBI in this population based on febrile infant population data and a general hesitance to begin antibiotics without first evaluating for IBI. They also cited a low prevalence ranging from 0.8% to 2.5% as evidence for low risk of IBI in afebrile infants with AOM.

Also of note, given that roughly three-fourths of infants included in the study were reported to have symptoms of upper respiratory infection that can lead to viral AOM, including these infants who could have a lower likelihood of IBI than those with known bacterial AOM, may have led the researchers to underestimate IBI prevalence. Because existing data do not allow for clear distinction of viral from bacterial AOM without tympanocentesis, and because more than 85% of older patients with clinically diagnosed AOM also have observed bacterial otopathogens, the authors clarify that “it is understandable why clinicians would manage infants with AOM conservatively, regardless of the presence of concurrent viral illnesses.” They also acknowledged that one major challenge in working with infants believed to have AOM is ensuring that it is actually present since it is so hard to diagnose.

Dr. McLaren and colleagues cited several study limitations: 1) completeness and accuracy of data couldn’t be ensured because of the retrospective study design; 2) because not all infants were tested for IBI, its prevalence may have been underestimated; 3) infants whose discharge codes did not include AOM may have been missed, although all infants with positive blood or cerebrospinal fluid cultures were screened for missed AOM diagnosis; and 4) it is important to consider that any issues associated with testing and hospitalization that were identified may have been the result of management decisions driven by factors that cannot be captured retrospectively or by a diagnosis of AOM.
 

The findings are not generalizable to infants aged younger than 28 days

Finally, the authors cautioned that because the number of infants younger than 28 days was quite small, and it is therefore infinitely more challenging to diagnose AOM for these patients, results of the study should be applied to infants older than 28 days and are not generalizable to febrile infants.

“This report will not resolve the significant challenge faced by clinicians in treating infants aged [younger than] 28 days who have the highest risk of occult bacteremia and systemic spread of a focal bacterial infection,” Joseph Ravera, MD, and M.W. Stevens, MD, of the University of Vermont, Burlington, noted in an accompanying editorial. Previous studies have identified this age group “to be at the highest risk for systemic bacterial involvement and the most difficult to risk stratify on the basis of physical examination findings and initial laboratory results,” they noted. That the subjects aged younger than 28 days in this study had nearly a 50% admission rate illustrates the clinical uncertainty pediatric emergency medicine providers are challenged with, they added. Just 100 (6%) of the 1,637 patients in the study sample were in this age category, which makes it difficult, given the lack of sufficient data, to generalize findings to the youngest infants.

“Despite a paucity of young infants and limitations inherent to the design, this study does contribute to the literature with a robust retrospective data set of afebrile infants between 1 and 3 months of age with an ED diagnosis of AOM ... It certainly provides a base of support for carefully designed prospective studies in which researchers aim to determine the best care for AOM in children under 6 months of age,” reflected Dr. Ravera and Dr. Stevens.

In a separate interview, Karalyn Kinsella, MD, private practice, Cheshire, Conn. noted, “What is confusing is the absence of documented symptoms for infants presenting to the emergency department, as the symptoms they presented with would influence our concern for IBI. Diagnosing AOM in infants under 90 days old is extremely uncommon as an outpatient pediatrician. Although the finding of AOM in an afebrile infant is very rare in the outpatient setting, this study assures us the risk of IBI is almost nonexistent. Therefore, further workup is unnecessary unless providers have clinical suspicions to the contrary.”

Dr. McLaren and colleagues as well as Dr. Ravera, Dr. Stevens, and Dr. Kinsella, had no conflicts of interest and no relevant financial disclosures.

Outpatient management of most afebrile infants with acute otitis media who haven’t been tested for invasive bacterial infection may be reasonable given the low occurrence of adverse events, said Son H. McLaren, MD, MS, of Columbia University, New York, and colleagues.

Dr. McLaren and associates conducted an international cross-sectional study at 33 emergency departments participating in the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics (AAP): 29 in the United States, 2 in Canada and 2 in Spain.

The researchers sought first to assess prevalence of invasive bacterial infections and adverse events tied to acute otitis media (AOM) in infants 90 days and younger. Those who were clinically diagnosed with AOM and presented without fever between January 2007 and December 2017 were included in the study. The presence of fever, they explained, “is a primary driver for more expanded testing and/or empirical treatment of invasive bacterial infection (IBI). Secondarily, they sought to characterize patterns of diagnostic testing and the factors associated with it specifically in this patient population.

Of 5,270 patients screened, 1,637 met study criteria. Included patients were a median age of 68 days. A total of 1,459 (89.1%) met AAP diagnostic criteria for AOM. The remaining 178 patients were examined and found to have more than one of these criteria: 113 had opacification of tympanic membrane, 57 had dull tympanic membrane, 25 had decreased visualization of middle ear structures, 9 had middle ear effusion, 8 had visible tympanic membrane perforation and 5 had decreased tympanic membrane mobility with insufflation. None of the 278 infants with blood cultures had bacteremia, nor were they diagnosed with bacterial meningitis. Two of 645 (0.3%) infants experienced adverse events, as evidenced with 30-day follow-up or history of hospitalization.

Dr. McLaren and colleagues observed that despite a low prevalence of IBI and AOM-associated adverse events, more than one-fifth of patients were prescribed diagnostic testing for IBI and subsequently hospitalized, a practice that appeared more common with younger patients.
 

Significant testing and hospitalizations persisted despite low prevalence of IBIs

Although diagnostic testing and hospitalizations differed by site, they were, in fact, “substantial in contrast to the low prevalence of IBIs and adverse events,” the researchers noted. “Our data may be used to help guide clinical management of afebrile infants with clinician-diagnosed AOM, who are not included in the current AAP AOM practice guideline,” the authors said. They speculated that this practice may be due, in part, to young-age risk of IBI and the concern for IBI in this population based on febrile infant population data and a general hesitance to begin antibiotics without first evaluating for IBI. They also cited a low prevalence ranging from 0.8% to 2.5% as evidence for low risk of IBI in afebrile infants with AOM.

Also of note, given that roughly three-fourths of infants included in the study were reported to have symptoms of upper respiratory infection that can lead to viral AOM, including these infants who could have a lower likelihood of IBI than those with known bacterial AOM, may have led the researchers to underestimate IBI prevalence. Because existing data do not allow for clear distinction of viral from bacterial AOM without tympanocentesis, and because more than 85% of older patients with clinically diagnosed AOM also have observed bacterial otopathogens, the authors clarify that “it is understandable why clinicians would manage infants with AOM conservatively, regardless of the presence of concurrent viral illnesses.” They also acknowledged that one major challenge in working with infants believed to have AOM is ensuring that it is actually present since it is so hard to diagnose.

Dr. McLaren and colleagues cited several study limitations: 1) completeness and accuracy of data couldn’t be ensured because of the retrospective study design; 2) because not all infants were tested for IBI, its prevalence may have been underestimated; 3) infants whose discharge codes did not include AOM may have been missed, although all infants with positive blood or cerebrospinal fluid cultures were screened for missed AOM diagnosis; and 4) it is important to consider that any issues associated with testing and hospitalization that were identified may have been the result of management decisions driven by factors that cannot be captured retrospectively or by a diagnosis of AOM.
 

The findings are not generalizable to infants aged younger than 28 days

Finally, the authors cautioned that because the number of infants younger than 28 days was quite small, and it is therefore infinitely more challenging to diagnose AOM for these patients, results of the study should be applied to infants older than 28 days and are not generalizable to febrile infants.

“This report will not resolve the significant challenge faced by clinicians in treating infants aged [younger than] 28 days who have the highest risk of occult bacteremia and systemic spread of a focal bacterial infection,” Joseph Ravera, MD, and M.W. Stevens, MD, of the University of Vermont, Burlington, noted in an accompanying editorial. Previous studies have identified this age group “to be at the highest risk for systemic bacterial involvement and the most difficult to risk stratify on the basis of physical examination findings and initial laboratory results,” they noted. That the subjects aged younger than 28 days in this study had nearly a 50% admission rate illustrates the clinical uncertainty pediatric emergency medicine providers are challenged with, they added. Just 100 (6%) of the 1,637 patients in the study sample were in this age category, which makes it difficult, given the lack of sufficient data, to generalize findings to the youngest infants.

“Despite a paucity of young infants and limitations inherent to the design, this study does contribute to the literature with a robust retrospective data set of afebrile infants between 1 and 3 months of age with an ED diagnosis of AOM ... It certainly provides a base of support for carefully designed prospective studies in which researchers aim to determine the best care for AOM in children under 6 months of age,” reflected Dr. Ravera and Dr. Stevens.

In a separate interview, Karalyn Kinsella, MD, private practice, Cheshire, Conn. noted, “What is confusing is the absence of documented symptoms for infants presenting to the emergency department, as the symptoms they presented with would influence our concern for IBI. Diagnosing AOM in infants under 90 days old is extremely uncommon as an outpatient pediatrician. Although the finding of AOM in an afebrile infant is very rare in the outpatient setting, this study assures us the risk of IBI is almost nonexistent. Therefore, further workup is unnecessary unless providers have clinical suspicions to the contrary.”

Dr. McLaren and colleagues as well as Dr. Ravera, Dr. Stevens, and Dr. Kinsella, had no conflicts of interest and no relevant financial disclosures.

Outpatient management of most afebrile infants with acute otitis media who haven’t been tested for invasive bacterial infection may be reasonable given the low occurrence of adverse events, said Son H. McLaren, MD, MS, of Columbia University, New York, and colleagues.

Dr. McLaren and associates conducted an international cross-sectional study at 33 emergency departments participating in the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics (AAP): 29 in the United States, 2 in Canada and 2 in Spain.

The researchers sought first to assess prevalence of invasive bacterial infections and adverse events tied to acute otitis media (AOM) in infants 90 days and younger. Those who were clinically diagnosed with AOM and presented without fever between January 2007 and December 2017 were included in the study. The presence of fever, they explained, “is a primary driver for more expanded testing and/or empirical treatment of invasive bacterial infection (IBI). Secondarily, they sought to characterize patterns of diagnostic testing and the factors associated with it specifically in this patient population.

Of 5,270 patients screened, 1,637 met study criteria. Included patients were a median age of 68 days. A total of 1,459 (89.1%) met AAP diagnostic criteria for AOM. The remaining 178 patients were examined and found to have more than one of these criteria: 113 had opacification of tympanic membrane, 57 had dull tympanic membrane, 25 had decreased visualization of middle ear structures, 9 had middle ear effusion, 8 had visible tympanic membrane perforation and 5 had decreased tympanic membrane mobility with insufflation. None of the 278 infants with blood cultures had bacteremia, nor were they diagnosed with bacterial meningitis. Two of 645 (0.3%) infants experienced adverse events, as evidenced with 30-day follow-up or history of hospitalization.

Dr. McLaren and colleagues observed that despite a low prevalence of IBI and AOM-associated adverse events, more than one-fifth of patients were prescribed diagnostic testing for IBI and subsequently hospitalized, a practice that appeared more common with younger patients.
 

Significant testing and hospitalizations persisted despite low prevalence of IBIs

Although diagnostic testing and hospitalizations differed by site, they were, in fact, “substantial in contrast to the low prevalence of IBIs and adverse events,” the researchers noted. “Our data may be used to help guide clinical management of afebrile infants with clinician-diagnosed AOM, who are not included in the current AAP AOM practice guideline,” the authors said. They speculated that this practice may be due, in part, to young-age risk of IBI and the concern for IBI in this population based on febrile infant population data and a general hesitance to begin antibiotics without first evaluating for IBI. They also cited a low prevalence ranging from 0.8% to 2.5% as evidence for low risk of IBI in afebrile infants with AOM.

Also of note, given that roughly three-fourths of infants included in the study were reported to have symptoms of upper respiratory infection that can lead to viral AOM, including these infants who could have a lower likelihood of IBI than those with known bacterial AOM, may have led the researchers to underestimate IBI prevalence. Because existing data do not allow for clear distinction of viral from bacterial AOM without tympanocentesis, and because more than 85% of older patients with clinically diagnosed AOM also have observed bacterial otopathogens, the authors clarify that “it is understandable why clinicians would manage infants with AOM conservatively, regardless of the presence of concurrent viral illnesses.” They also acknowledged that one major challenge in working with infants believed to have AOM is ensuring that it is actually present since it is so hard to diagnose.

Dr. McLaren and colleagues cited several study limitations: 1) completeness and accuracy of data couldn’t be ensured because of the retrospective study design; 2) because not all infants were tested for IBI, its prevalence may have been underestimated; 3) infants whose discharge codes did not include AOM may have been missed, although all infants with positive blood or cerebrospinal fluid cultures were screened for missed AOM diagnosis; and 4) it is important to consider that any issues associated with testing and hospitalization that were identified may have been the result of management decisions driven by factors that cannot be captured retrospectively or by a diagnosis of AOM.
 

The findings are not generalizable to infants aged younger than 28 days

Finally, the authors cautioned that because the number of infants younger than 28 days was quite small, and it is therefore infinitely more challenging to diagnose AOM for these patients, results of the study should be applied to infants older than 28 days and are not generalizable to febrile infants.

“This report will not resolve the significant challenge faced by clinicians in treating infants aged [younger than] 28 days who have the highest risk of occult bacteremia and systemic spread of a focal bacterial infection,” Joseph Ravera, MD, and M.W. Stevens, MD, of the University of Vermont, Burlington, noted in an accompanying editorial. Previous studies have identified this age group “to be at the highest risk for systemic bacterial involvement and the most difficult to risk stratify on the basis of physical examination findings and initial laboratory results,” they noted. That the subjects aged younger than 28 days in this study had nearly a 50% admission rate illustrates the clinical uncertainty pediatric emergency medicine providers are challenged with, they added. Just 100 (6%) of the 1,637 patients in the study sample were in this age category, which makes it difficult, given the lack of sufficient data, to generalize findings to the youngest infants.

“Despite a paucity of young infants and limitations inherent to the design, this study does contribute to the literature with a robust retrospective data set of afebrile infants between 1 and 3 months of age with an ED diagnosis of AOM ... It certainly provides a base of support for carefully designed prospective studies in which researchers aim to determine the best care for AOM in children under 6 months of age,” reflected Dr. Ravera and Dr. Stevens.

In a separate interview, Karalyn Kinsella, MD, private practice, Cheshire, Conn. noted, “What is confusing is the absence of documented symptoms for infants presenting to the emergency department, as the symptoms they presented with would influence our concern for IBI. Diagnosing AOM in infants under 90 days old is extremely uncommon as an outpatient pediatrician. Although the finding of AOM in an afebrile infant is very rare in the outpatient setting, this study assures us the risk of IBI is almost nonexistent. Therefore, further workup is unnecessary unless providers have clinical suspicions to the contrary.”

Dr. McLaren and colleagues as well as Dr. Ravera, Dr. Stevens, and Dr. Kinsella, had no conflicts of interest and no relevant financial disclosures.