Pediatric News

Contrary to common belief, potatoes do not have a negative effect on blood glucose levels and can actually help people lose weight, according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

What to know

Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.

People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.

Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.

Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.

People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.

This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.

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

Contrary to common belief, potatoes do not have a negative effect on blood glucose levels and can actually help people lose weight, according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

What to know

Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.

People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.

Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.

Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.

People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.

This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.

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

Contrary to common belief, potatoes do not have a negative effect on blood glucose levels and can actually help people lose weight, according to researchers at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

What to know

Potatoes are filled with key nutrients, packed with health benefits, and do not increase the risk of type 2 diabetes, as has been assumed.

People tend to eat the same weight of food regardless of calorie content to feel full, so by eating foods that are heavier in weight and that are low in calories, you can reduce the number of calories you consume.

Study participants found themselves fuller, and full more quickly, and often did not even finish their meal when the high-calorie items of their meals were replaced with potatoes.

Participants had overweight, obesity, or insulin resistance, but their blood glucose levels were not negatively affected by the potato consumption, and all of those involved actually lost weight.

People typically do not stick with a diet they don’t like or that isn't varied enough, but potatoes can be prepared in numerous ways for variety in a diet, and they are a fairly inexpensive vegetable to incorporate into a diet.

This is a summary of the article, "Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial," published in the Journal of Medicinal Food on November 11, 2022. The full article can be found on pubmed.ncbi.nlm.nih.gov.

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

As physicians well know, magic wands don’t exist. If they did, every patient would recover in the exam room, prior authorization wouldn’t exist, and continuing medical education credits would be printed on bearer bonds.

But in the spirit of suspended disbelief, we asked physicians and other contributors what their three wishes would be for their patients, practice/hospital, and health systems. Because, hey – we all need to dream.
 

Suzanne C. Boulter, MD, adjunct professor of pediatrics and community and family medicine, Geisel School of Medicine at Dartmouth, Hanover, N.H.
Patients: An end to gun violence.
Practice/hospital: Adequate staffing and pediatric bed availability.
Health system: Universal access to health insurance.

Sarah G. Candler, MD, MPH, care team medical director and director of academic relations, Iora Primary Care, Northside Clinic, Houston
Patients: Systems of health that start with communities of safety, including access to affordable housing, food, transportation, and health care.
Practice/hospital: I.N.T.E.R.O.P.E.R.A.B.I.L.I.T.Y.
Health system: Clinician leadership that has the power (often aka funding) to do what’s right, not just what’s right in front of us.

Arthur L. Caplan, PhD, bioethicist, New York University Langone Health
Patients: I wish for patients in the United States greater access to affordable primary care. There are still too many people without insurance or a reasonably accessible quality provider. And I especially wish for the rapid expansion of affordable training programs to meet staffing needs, including more scholarships, 3-year programs, and more new primary care–oriented schools.
Hospital: Increased staffing, especially nursing. There are too many retirements, too much burnout, and too much privatization into boutique practices to ensure the ability to provide high-quality, safe, patient-oriented care.
Health system: I wish for health systems to seriously move into electronic medicine. While billing has become electronic, there is still much to be done to supplement diagnosis, training, and standardized data collection on key metrics. Systems are not yet behaving in a manner consistent with the hype in this regard.

Stephen Devries, MD, executive director, Gaples Institute (nonprofit) and adjunct associate professor of nutrition, Harvard School of Public Health, Boston
Patients: Patients continue to demand more from their health care professionals and insist that they are offered evidence-based counseling on nutrition and lifestyle strategies.
Practice: Quality-based reimbursement for medical services will take hold that will incentivize much-needed preventive care.
Hospital: Hospitals will more fully embrace the role of serving as true centers of health and focus as much on preventive medicine as on the more lucrative areas of high-tech treatment.

Peter D. Friedmann, MD, MPH, chief research officer, Baystate Health, Springfield, Mass.
Seconded by: Elisabeth Poorman, MD, general internist, University of Washington Clinic, Kent
Patients: Don’t forget the ongoing epidemic of substance use disorder, a major cause of premature mortality. Descheduling of cannabis and expungement of cannabis-related convictions.
Practice/hospital: Commitment of hospitals and practices to address stigma and ensure delivery of medications for opioid use disorder in primary care, the emergency department, and inpatient settings.
Health system: Reform of antiquated methadone regulations to permit office-based prescription and pharmacy dispensing to treat opioid use disorder, as is the case in most of the world.

Robert Glatter, MD, emergency physician, New York
Patients: I want all patients to understand the enormous strain the health care system has been under – not just with the pandemic, the tripledemic, and mpox [previously called monkeypox], but well before the onset of these public health crises.
Hospital: The medical profession has endured not only burnout but a growing mental health crisis, staffing shortages, a physician addiction crisis, and increased attrition in the decade leading up to the pandemic. The pandemic was like a punch in the gut, occurring at the most inopportune time one could imagine.
Health system: The intersection of health and the state of our public health deserves important mention. Unless we take action to bolster our public health infrastructure, our health care system will be in jeopardy, unable to handle the next pandemic, which could be just around the corner.

William E. Golden, MD, medical director of Arkansas Medicaid, professor of medicine and public health, University of Arkansas for Medical Sciences, Little Rock
Patients: Affordable options for diabetes and obesity management.
Health system: Greater investment by health systems and third-party payers in primary care infrastructure.

Gregory A. Hood, MD, Baptist Health, Lexington, Ky.
Patients: To embrace the gift of getting out in the world, being active, and connecting with others – having put down the screens.
Health system: To be freed from the financial gamesmanship of the insurers as they continue to serve their goals of promoting their hedge fund investing over meaningful and productive partnering with primary care physicians, and that they gain insight that they are one of the main reasons they can’t find PCPs to connect with to render care in disadvantaged environments – because they made it economically impossible to do so.

Robert H. Hopkins Jr., MD, associate professor of internal medicine and pediatrics and director of the division of general internal medicine, University of Arkansas for Medical Sciences, Little Rock
Patients/Health system: I would wish for staged implementation of universal basic health coverage for all, perhaps closest to the French or Canadian model. This would need to be coupled with expanded funding for nursing education, graduate medical education, and tracing of other health-related professionals.

Harvey Hsu, MD, Banner Health, Phoenix
Patients: More clear guidelines that are simple to understand. This can apply to colonoscopy (now age 45), immunizations, blood pressure goals. I wish medications were not as expensive so patients can take the best medicine for them and not stop taking them when they hit their donut hole in coverage.
Practice: We have been functioning on a leaner basis to cut down costs. When the pandemic hit, turnover was high and we lost PAs, nurses, front-office staff, and physicians. Having adequate staffing is probably number one on many lists. One way we dealt with lack of staffing was converting in-person visits to telehealth. Video visits are paid the same as in-person visits, but if the patient could not get their video to work, then it would be a telephone visit. Now many insurances do not even pay for telephone visits. So I would wish that we could still be reimbursed for telehealth visits.
Health system: I would wish for our health system to recognize the extra work required to take care of patients while improving quality and meeting quality measures. Allowing more time for patient visits could be one way to meet those goals or having more support staff to make sure patients get their colonoscopy/mammograms done, improve their sugars, and take their medications.

Jan L. Shifren, MD, Vincent Trustees Professor, obstetrics, gynecology, and reproductive biology, Harvard Medical School, and director of the Midlife Women’s Health Center at Massachusetts General Hospital, Boston
Patients: I wish for patients to be actively involved in all aspects of their care, well informed with shared decision-making.
Practice: I wish for the enormous time demands of electronic medical records and documentation to not distract from the pleasure of caring for patients.
Health system: Patient care remains at the center of decisions and programs.

Timothy J. Joos, MD, MPH, internal medicine/pediatrics, Seattle
Health system: I wish someone could figure out how we could be reimbursed for the quality of care we provide instead of the volume of patients we see. I wish EMRs could become less complicated and more user-friendly rather than needing advanced training to use.

Peter Kovacs, MD, medical director, Kaali Institute IVF Center, Budapest
Patients: I work as an infertility specialist, so when we talk about infectious diseases and associated risks, we talk about a minimum of two (female and male partner) and ideally three (plus the pregnancy) individuals. We have learned that SARS-CoV-2 affects reproductive health. It may compromise sperm production, could delay fertility treatment, could be associated with lower success rates; and if the treatment is successful, it may harm the pregnant woman/fetus/newborn. The best preventive measure that we can offer is vaccination. One cannot overemphasize the importance of preventive measures, paying attention to personal hygiene and social distancing. Therefore, I wish those planning to become pregnant to listen to their health care provider and accept the recommended vaccines to minimize the risk of getting infected and to minimize the risk for severe disease, especially if one undergoes successful fertility treatment and achieves a long-desired pregnancy.
Practice: During the 2022 calendar year we had many days when one or more employees were out of work on sick leave. This puts extra stress on the others to allow uncompromised work in the clinic. In addition, we all have to work in a less-comfortable environment if we consider mask use every day, all day. For health care workers, vaccination is mandated but many still are affected by milder forms of coronavirus infection and other respiratory diseases. Therefore, I wish my colleagues patience toward the preventive measures to lower the individual risk for infections. As a result, hopefully we will have a less stressful 2023.
Health system: Many resources had to be delegated to dealing with acute and chronic COVID, and this was at the expense of routine daily elective and preventive medical services. I wish the health care system to return to normal daily operations, to have the personnel and financial resources to carry on with the required preventive and elective medical services to avoid long-term consequences of not being able to provide such services. It would be sad if we had to treat otherwise preventable illnesses in the upcoming years that went undiagnosed and/or were not properly managed due to limited resources as the result of the pandemic.

Alan R. Nelson, MD, internist-endocrinologist, retired
Patients: Expansion of the FDA’s authority into over-the-counter drugs, including the veracity of their advertising claims.
Practice: Make diabetes drugs available at a reasonable cost.
Health system: With the expansion of Medicaid eligibility during COVID-19 coming to a close, federal government actions are necessary for those who once again have been dropped from coverage to have their legitimate needs met.

Kevin Powell, MD, PhD, St. Louis
Patients: To be cared for and about, and not just medically, even when illness strikes and health fails.
Hospitals: To hear the thankfulness of a grateful public for the care you provide, and to hear that above the angry noise of outraged individuals who spout vitriol and focus on how they believe others have harmed them.
Health system: A truer understanding of mercy and justice.

Margaret Thew, DNP, FNP-BC, director, department of adolescent medicine, Children’s Hospital of Wisconsin, Milwaukee
Seconded by: M. Susan Jay, MD, professor of pediatrics, chief of adolescent medicine, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee
My wish for patients, hospital, and system: health, calm, and grace.

Mark P. Trolice, MD, director of Fertility CARE, the IVF Center, Winter Park, Fla.
Patients: To be proactive in their health care and be their own advocates. Question when unclear and only consult credible resources.
Practice/hospital: Improve support of physicians and all health care providers to allow more input in their practice operations and growth.
Health system: Reduce interference of the “business of medicine” and ensure that the patient experience is the priority.

Charles P. Vega, MD, University of California, Irvine
Three minutes on a routine basis for everyone in health care to reflect on our blessings and the honor and gravity – as well as joy – that are integral to health care. Three minutes that will also help us to recognize our challenges and put them in the proper context. I know 3 minutes is not meeting any standard for reflective practice. But it’s 3 minutes more than I have right now.

Karen Breach Washington, MD, medical director of WellCare of North Carolina/Centene, Charlotte
Seconded by: Lillian M. Beard, MD, physician director, Children’s Pediatricians and Associates, Silver Spring, Md.
Patients: Access to affordable health care.
Hospital: Resources to care for patients (sufficient number of beds and a healthy staff).
Health system: Equity for all.

Andrew Wilner, MD, host of the podcast “The Art of Medicine with Dr. Andrew Wilner,” www.andrewwilner.com
Let’s put patients first! Too many extraneous considerations other than the patient’s best interest obstruct optimal patient care.

Here are just a few examples of patients coming last instead of first.

• If a patient needs to start a new medication in hospital, we shouldn’t have to wait until the patient is an outpatient because “that’s when insurance will pay.”
• If there’s a new medication that’s better than the old medication, we shouldn’t be forced to choose the old medication and provide inferior care because “that’s when insurance will pay.”
• If patients need to stay in hospital, we shouldn’t be pressured to discharge them because the hospital has decided that decreasing “length of stay” is its highest priority.

Dr. Francis Peabody said it best in 1927: “The secret of the care of the patient is in caring for the patient.” How hard is that?

In 2023, why don’t we follow Dr. Peabody’s sage advice from nearly 100 years ago and see what happens?
 

James M. Wooten, PharmD, University of Missouri–Kansas City, University Health, Kansas City, Mo.
Patients: I want patients to understand and properly realize the advantage of vaccinations – not only for COVID-19 but also for influenza. There is so much misinformation that I spend a lot of time trying to convince patients to get vaccinated. Most patients don’t realize that through their lives, most of them have already been vaccinated for something just to be able to attend school. How the COVID-19 vaccine created so much stigma makes little sense to me. I also want patients to understand that COVID-19 vaccination and boosters do not always prevent infection but will many times prevent severe infection. I believe that better patient communication and education is the key and will always be the key to improving vaccination numbers. Not only communicating and educating patients on vaccination itself but also making patients realize that personal vaccination decisions may affect what happens to your neighbor. Allowing infection means that you may be more likely to infect someone else. As a society, we must take care of each other.
Health system: It will be interesting to see what happens when vaccines are no longer reimbursed by the federal government. Understanding which vaccines work best and are better tolerated will be key to choosing appropriate vaccine brands. Health care providers will need to be very selective regarding which vaccines are selected for formulary inclusion. Thorough meta-analysis studies must be done to provide more evaluable information to allow for appropriate selection. “Knowledge is power!” Appropriate knowledge will help distinguish which vaccines work best for various patient populations.

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Pigs have been long used in medical schools to teach surgical techniques and, more recently, in research trials and experimental xenotransplantation procedures. But given the rise of alternative simulation technology and mounting pressure from animal rights groups and lawmakers, animal labs for medical training have become less common.

Just last month, the Physicians Committee for Responsible Medicine, a nonprofit group with a decades-long stance against the use of animals in medical education and research, placed billboards around the Portland, Ore., area demanding that Oregon Health and Science University stop using pigs to teach surgical residents.

Undergraduate medical programs no longer use live animals. But a small number of graduate medical education programs still use animals, predominantly pigs, to train physicians in subspecialties like internal medicine, emergency medicine, surgery, and anesthesiology, John Pippin, MD, FACC, director of academic affairs at PCRM, told this news organization.

Dr. Pippin says residents practice establishing emergency airways, inserting chest tubes, and accessing blood vessels on anesthetized pigs before euthanizing them.

Swine lab advocates say pigs make ideal training subjects because of their similarities to humans, including comparably sized organs like the heart, lungs, and kidneys. Pigs share about 85% of their DNA with people. Where pig skin alternatives may suffice for less invasive procedures, supporters say residents’ experiences with live tissue are irreplaceable.

In a statement, Sara Hottman, associate director of media relations at Oregon Health and Science University, told this news organization the school “only uses animal models in its surgical training program when nonanimal methods are inadequate or too dangerous for human participants.”

“We believe that the education and experience surgical trainees gain through the use of relevant animal models are essential to ensuring future surgeons have the knowledge and skills necessary to provide safe, high-quality care.”

Ms. Hottman also noted that the university continues to evaluate alternatives and looks forward to when nonanimal “surgical training methods are capable of faithfully modeling the complexity of a living system,” such as in the management of critical internal complications.

But Dr. Pippin argues that residents can gain sufficient expertise through simulators and hands-on training in the operating room, and that the differences between humans and pigs are too vast to provide meaningful clinical data or skills.

“Pigs have different genetic influences and very thick, tough skin,” he said. If you use the same pressure on a human that you learned on a pig, he added, “you’d slice right through the trachea. Whatever you think you find out in animals, you have to learn all over again with humans.”

Undergraduate medical education programs in the United States and Canada abandoned the practice of using live animals, including pigs, by 2016, with Johns Hopkins University, Baltimore, and the University of Tennessee, Chattanooga, last to announce their shift away from the controversial teaching model following campaigns by PCRM.

Today, most residency training programs have followed suit. Pippin said that pediatric residencies no longer use animals, and all trauma and anesthesiology programs have ceased such practices except two. Just 3% of emergency medicine programs continue to use animals, as do about 21% of surgical residencies, he said, based on PCRM’s latest surveys.
 

A public debate

Occasionally, PCRM goes public with a campaign against a residency program “if that’s the only way to win,” Dr. Pippin said.

In addition to billboards, the group has held protests, circulated petitions, and filed complaints with the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, the entity responsible for overseeing the health and welfare of animals used in medical training and research.

In 2021, spurred by a complaint from PCRM, APHIS launched an investigation into the University of Cincinnati’s surgical residency program. At the time, a university spokesperson acknowledged the school’s limited use of pigs to train “highly-skilled, well-prepared surgeons in the most advanced, complex, real-world needs, procedures, and techniques,” adding that the training methods were endorsed by the American College of Surgeons and in compliance with federal guidelines.

Residency programs have caught the attention of state lawmakers, too. In 2020, bills introduced in both the Rhode Island House and Senate sought to ban the use of live animals in medical training when “there is an alternate teaching method that teaches the medical procedure or lesson without the use of an animal.” Violators would incur misdemeanor charges and monetary fines of up to $1,000 per animal.

The bills – backed by PCRM – targeted Brown University’s emergency medicine residency program, Providence, R.I., which sponsoring legislators said was the last program in New England still using the “outdated” and “unnecessary” method.

In testimony before lawmakers, the school said fewer than 15 pigs participate in the annual training, and faculty spoke about the benefits of the experience.

“If it was your brother or sister, or your mother or father who had to come in and get this procedure done, would you want the physician who’s doing it to be the one who does it for the very first time on a human being, on live tissue? Or do you want that provider to have only practiced on plastic and rubber?” said Nicholas Musisca, MD, an assistant program director with Brown University’s emergency medicine residency, NBC affiliate WJAR reported.

The bills have since stalled, and PCRM held a protest at Brown University in October 2022. In response, a university spokesperson told the Brown Daily Herald, “effective synthetic model alternatives simply do not exist for every complex medical procedure that an emergency physician must be prepared to perform,” including establishing an airway in adults and pediatric patients with severe facial trauma.
 

By the numbers

Annual reports from APHIS do not show the number of pigs dedicated solely to residency training. Instead, reporting indicates the number of animals “upon which experiments, teaching, research, surgery, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic, or tranquilizing drugs were used.”

For fiscal year 2021 – the most recent data available – Oregon Health and Science University had 154 pigs under its control, while the University of Cincinnati and Brown University had 118 and 71 pigs, respectively, according to APHIS. Primates were more commonly used at Oregon Health and Science University and guinea pigs at the University of Cincinnati.

Similarly, the Association of American Medical Colleges supports the “use of animals to meet essential educational objectives [across] the medical education continuum. ... Further restrictions on the use of animals in biomedical and behavioral research and education threatens progress in health care and disease prevention.”

The debate will likely rage on. “The one thing we don’t do is give up,” Dr. Pippin said.

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

Pigs have been long used in medical schools to teach surgical techniques and, more recently, in research trials and experimental xenotransplantation procedures. But given the rise of alternative simulation technology and mounting pressure from animal rights groups and lawmakers, animal labs for medical training have become less common.

Just last month, the Physicians Committee for Responsible Medicine, a nonprofit group with a decades-long stance against the use of animals in medical education and research, placed billboards around the Portland, Ore., area demanding that Oregon Health and Science University stop using pigs to teach surgical residents.

Undergraduate medical programs no longer use live animals. But a small number of graduate medical education programs still use animals, predominantly pigs, to train physicians in subspecialties like internal medicine, emergency medicine, surgery, and anesthesiology, John Pippin, MD, FACC, director of academic affairs at PCRM, told this news organization.

Dr. Pippin says residents practice establishing emergency airways, inserting chest tubes, and accessing blood vessels on anesthetized pigs before euthanizing them.

Swine lab advocates say pigs make ideal training subjects because of their similarities to humans, including comparably sized organs like the heart, lungs, and kidneys. Pigs share about 85% of their DNA with people. Where pig skin alternatives may suffice for less invasive procedures, supporters say residents’ experiences with live tissue are irreplaceable.

In a statement, Sara Hottman, associate director of media relations at Oregon Health and Science University, told this news organization the school “only uses animal models in its surgical training program when nonanimal methods are inadequate or too dangerous for human participants.”

“We believe that the education and experience surgical trainees gain through the use of relevant animal models are essential to ensuring future surgeons have the knowledge and skills necessary to provide safe, high-quality care.”

Ms. Hottman also noted that the university continues to evaluate alternatives and looks forward to when nonanimal “surgical training methods are capable of faithfully modeling the complexity of a living system,” such as in the management of critical internal complications.

But Dr. Pippin argues that residents can gain sufficient expertise through simulators and hands-on training in the operating room, and that the differences between humans and pigs are too vast to provide meaningful clinical data or skills.

“Pigs have different genetic influences and very thick, tough skin,” he said. If you use the same pressure on a human that you learned on a pig, he added, “you’d slice right through the trachea. Whatever you think you find out in animals, you have to learn all over again with humans.”

Undergraduate medical education programs in the United States and Canada abandoned the practice of using live animals, including pigs, by 2016, with Johns Hopkins University, Baltimore, and the University of Tennessee, Chattanooga, last to announce their shift away from the controversial teaching model following campaigns by PCRM.

Today, most residency training programs have followed suit. Pippin said that pediatric residencies no longer use animals, and all trauma and anesthesiology programs have ceased such practices except two. Just 3% of emergency medicine programs continue to use animals, as do about 21% of surgical residencies, he said, based on PCRM’s latest surveys.
 

A public debate

Occasionally, PCRM goes public with a campaign against a residency program “if that’s the only way to win,” Dr. Pippin said.

In addition to billboards, the group has held protests, circulated petitions, and filed complaints with the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, the entity responsible for overseeing the health and welfare of animals used in medical training and research.

In 2021, spurred by a complaint from PCRM, APHIS launched an investigation into the University of Cincinnati’s surgical residency program. At the time, a university spokesperson acknowledged the school’s limited use of pigs to train “highly-skilled, well-prepared surgeons in the most advanced, complex, real-world needs, procedures, and techniques,” adding that the training methods were endorsed by the American College of Surgeons and in compliance with federal guidelines.

Residency programs have caught the attention of state lawmakers, too. In 2020, bills introduced in both the Rhode Island House and Senate sought to ban the use of live animals in medical training when “there is an alternate teaching method that teaches the medical procedure or lesson without the use of an animal.” Violators would incur misdemeanor charges and monetary fines of up to $1,000 per animal.

The bills – backed by PCRM – targeted Brown University’s emergency medicine residency program, Providence, R.I., which sponsoring legislators said was the last program in New England still using the “outdated” and “unnecessary” method.

In testimony before lawmakers, the school said fewer than 15 pigs participate in the annual training, and faculty spoke about the benefits of the experience.

“If it was your brother or sister, or your mother or father who had to come in and get this procedure done, would you want the physician who’s doing it to be the one who does it for the very first time on a human being, on live tissue? Or do you want that provider to have only practiced on plastic and rubber?” said Nicholas Musisca, MD, an assistant program director with Brown University’s emergency medicine residency, NBC affiliate WJAR reported.

The bills have since stalled, and PCRM held a protest at Brown University in October 2022. In response, a university spokesperson told the Brown Daily Herald, “effective synthetic model alternatives simply do not exist for every complex medical procedure that an emergency physician must be prepared to perform,” including establishing an airway in adults and pediatric patients with severe facial trauma.
 

By the numbers

Annual reports from APHIS do not show the number of pigs dedicated solely to residency training. Instead, reporting indicates the number of animals “upon which experiments, teaching, research, surgery, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic, or tranquilizing drugs were used.”

For fiscal year 2021 – the most recent data available – Oregon Health and Science University had 154 pigs under its control, while the University of Cincinnati and Brown University had 118 and 71 pigs, respectively, according to APHIS. Primates were more commonly used at Oregon Health and Science University and guinea pigs at the University of Cincinnati.

Similarly, the Association of American Medical Colleges supports the “use of animals to meet essential educational objectives [across] the medical education continuum. ... Further restrictions on the use of animals in biomedical and behavioral research and education threatens progress in health care and disease prevention.”

The debate will likely rage on. “The one thing we don’t do is give up,” Dr. Pippin said.

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

Pigs have been long used in medical schools to teach surgical techniques and, more recently, in research trials and experimental xenotransplantation procedures. But given the rise of alternative simulation technology and mounting pressure from animal rights groups and lawmakers, animal labs for medical training have become less common.

Just last month, the Physicians Committee for Responsible Medicine, a nonprofit group with a decades-long stance against the use of animals in medical education and research, placed billboards around the Portland, Ore., area demanding that Oregon Health and Science University stop using pigs to teach surgical residents.

Undergraduate medical programs no longer use live animals. But a small number of graduate medical education programs still use animals, predominantly pigs, to train physicians in subspecialties like internal medicine, emergency medicine, surgery, and anesthesiology, John Pippin, MD, FACC, director of academic affairs at PCRM, told this news organization.

Dr. Pippin says residents practice establishing emergency airways, inserting chest tubes, and accessing blood vessels on anesthetized pigs before euthanizing them.

Swine lab advocates say pigs make ideal training subjects because of their similarities to humans, including comparably sized organs like the heart, lungs, and kidneys. Pigs share about 85% of their DNA with people. Where pig skin alternatives may suffice for less invasive procedures, supporters say residents’ experiences with live tissue are irreplaceable.

In a statement, Sara Hottman, associate director of media relations at Oregon Health and Science University, told this news organization the school “only uses animal models in its surgical training program when nonanimal methods are inadequate or too dangerous for human participants.”

“We believe that the education and experience surgical trainees gain through the use of relevant animal models are essential to ensuring future surgeons have the knowledge and skills necessary to provide safe, high-quality care.”

Ms. Hottman also noted that the university continues to evaluate alternatives and looks forward to when nonanimal “surgical training methods are capable of faithfully modeling the complexity of a living system,” such as in the management of critical internal complications.

But Dr. Pippin argues that residents can gain sufficient expertise through simulators and hands-on training in the operating room, and that the differences between humans and pigs are too vast to provide meaningful clinical data or skills.

“Pigs have different genetic influences and very thick, tough skin,” he said. If you use the same pressure on a human that you learned on a pig, he added, “you’d slice right through the trachea. Whatever you think you find out in animals, you have to learn all over again with humans.”

Undergraduate medical education programs in the United States and Canada abandoned the practice of using live animals, including pigs, by 2016, with Johns Hopkins University, Baltimore, and the University of Tennessee, Chattanooga, last to announce their shift away from the controversial teaching model following campaigns by PCRM.

Today, most residency training programs have followed suit. Pippin said that pediatric residencies no longer use animals, and all trauma and anesthesiology programs have ceased such practices except two. Just 3% of emergency medicine programs continue to use animals, as do about 21% of surgical residencies, he said, based on PCRM’s latest surveys.
 

A public debate

Occasionally, PCRM goes public with a campaign against a residency program “if that’s the only way to win,” Dr. Pippin said.

In addition to billboards, the group has held protests, circulated petitions, and filed complaints with the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, the entity responsible for overseeing the health and welfare of animals used in medical training and research.

In 2021, spurred by a complaint from PCRM, APHIS launched an investigation into the University of Cincinnati’s surgical residency program. At the time, a university spokesperson acknowledged the school’s limited use of pigs to train “highly-skilled, well-prepared surgeons in the most advanced, complex, real-world needs, procedures, and techniques,” adding that the training methods were endorsed by the American College of Surgeons and in compliance with federal guidelines.

Residency programs have caught the attention of state lawmakers, too. In 2020, bills introduced in both the Rhode Island House and Senate sought to ban the use of live animals in medical training when “there is an alternate teaching method that teaches the medical procedure or lesson without the use of an animal.” Violators would incur misdemeanor charges and monetary fines of up to $1,000 per animal.

The bills – backed by PCRM – targeted Brown University’s emergency medicine residency program, Providence, R.I., which sponsoring legislators said was the last program in New England still using the “outdated” and “unnecessary” method.

In testimony before lawmakers, the school said fewer than 15 pigs participate in the annual training, and faculty spoke about the benefits of the experience.

“If it was your brother or sister, or your mother or father who had to come in and get this procedure done, would you want the physician who’s doing it to be the one who does it for the very first time on a human being, on live tissue? Or do you want that provider to have only practiced on plastic and rubber?” said Nicholas Musisca, MD, an assistant program director with Brown University’s emergency medicine residency, NBC affiliate WJAR reported.

The bills have since stalled, and PCRM held a protest at Brown University in October 2022. In response, a university spokesperson told the Brown Daily Herald, “effective synthetic model alternatives simply do not exist for every complex medical procedure that an emergency physician must be prepared to perform,” including establishing an airway in adults and pediatric patients with severe facial trauma.
 

By the numbers

Annual reports from APHIS do not show the number of pigs dedicated solely to residency training. Instead, reporting indicates the number of animals “upon which experiments, teaching, research, surgery, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic, or tranquilizing drugs were used.”

For fiscal year 2021 – the most recent data available – Oregon Health and Science University had 154 pigs under its control, while the University of Cincinnati and Brown University had 118 and 71 pigs, respectively, according to APHIS. Primates were more commonly used at Oregon Health and Science University and guinea pigs at the University of Cincinnati.

Similarly, the Association of American Medical Colleges supports the “use of animals to meet essential educational objectives [across] the medical education continuum. ... Further restrictions on the use of animals in biomedical and behavioral research and education threatens progress in health care and disease prevention.”

The debate will likely rage on. “The one thing we don’t do is give up,” Dr. Pippin said.

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

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

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

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

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

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

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

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

Rawpixel

Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

Rawpixel

Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

Rawpixel

Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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