Clinical Endocrinology News

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

Physicians are going to have to play catch-up when it comes to getting older patients their routine, but important, vaccinations missed during the pandemic.

©Sean Warren/iStockphoto.com

Weekly general vaccination among Medicare beneficiaries aged ≥ 65 year fell by around 80% soon after the national COVID-19 emergency declaration and have recovered only partially and gradually, according to a report by Kai Hong, PhD, and colleagues at the Centers for Disease Control and Prevention, published in the Morbidity and Mortality Weekly Report. “As the pandemic continues,” the investigators stated, “vaccination providers should continue efforts to resolve disruptions in routine adult vaccination.”

The CDC issued guidance recommending postponement of routine adult vaccination in response to the March 13, 2020, COVID-19 national emergency declaration by the U.S. government and also to state and local shelter-in-place orders. Health care facility operations were restricted because of safety concerns around exposure to the SARS-CoV-2 virus. The result was a significant drop in routine medical care including adult vaccinations.

The investigators examined Medicare enrollment and claims data to assess the change in weekly receipt of four routine adult vaccines by Medicare beneficiaries aged ≥65 during the pandemic: (13-valent pneu­mococcal conjugate vaccine [PCV13], 23-valent pneumococ­cal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]). The comparison periods were Jan. 6–July 20, 2019, and Jan. 5–July 18, 2020.

Of the Medicare enrollees in the study sample, 85% were White, 7% Black, 2% Asian, 2% Hispanic, and 4% other racial and ethnic groups. For each of the four vaccines overall, weekly rates of vaccination declined sharply after the emergency declaration, compared with corresponding weeks in 2019. In the period prior to the emergency declaration (Jan. 5–March 14, 2020), weekly percentages of Medicare beneficiaries vaccinated with PPSV23, Td/Tdap, and RZV were consistently higher than rates during the same period in 2019.

After the March 13 declaration, while weekly vaccination rates plummeted 25% for PPSV23 and 62% for RZV in the first week, the greatest weekly declines were during April 5-11, 2020, for PCV13, PPSV23, and Td/Tdap, and during April 12-18, 2020, for RZV. The pandemic weekly vaccination rate nadirs revealed declines of 88% for PCV13, 80% for PPSV23, 70% for Td/Tdap, and 89% for RZV.
 

Routine vaccinations increased midyear

Vaccination rates recovered gradually. For the most recently assessed pandemic week (July 12-18, 2020), the rate for PPSV23 was 8% higher than in the corresponding period in 2019. Weekly corresponding rates for other examined vaccines, however, remained much lower than in 2019: 44% lower for RZV, 24% lower for Td/Tdap and 43% lower for PCV13. The CDC Advisory Committee on Immunization Practices voted in June 2019 to stop recommending PCV13 for adults aged ≥65 years and so vaccination with PCV13 among this population declined in 2020, compared with that in 2019.

Another significant drop in the rates of adult vaccinations may have occurred because of the surge in COVID-19 infections in the fall of 2020 and subsequent closures and renewal of lockdown in many localities.
 

Disparities in routine vaccination trends

Dr. Hong and colleagues noted that their findings are consistent with prior reports of declines in pediatric vaccine ordering, administration, and coverage during the pandemic. While the reductions were similar across all racial and ethnic groups, the magnitudes of recovery varied, with vaccination rates lower among racial and ethnic minority adults than among White adults.

Physicians are going to have to play catch-up when it comes to getting older patients their routine, but important, vaccinations missed during the pandemic.

©Sean Warren/iStockphoto.com

Weekly general vaccination among Medicare beneficiaries aged ≥ 65 year fell by around 80% soon after the national COVID-19 emergency declaration and have recovered only partially and gradually, according to a report by Kai Hong, PhD, and colleagues at the Centers for Disease Control and Prevention, published in the Morbidity and Mortality Weekly Report. “As the pandemic continues,” the investigators stated, “vaccination providers should continue efforts to resolve disruptions in routine adult vaccination.”

The CDC issued guidance recommending postponement of routine adult vaccination in response to the March 13, 2020, COVID-19 national emergency declaration by the U.S. government and also to state and local shelter-in-place orders. Health care facility operations were restricted because of safety concerns around exposure to the SARS-CoV-2 virus. The result was a significant drop in routine medical care including adult vaccinations.

The investigators examined Medicare enrollment and claims data to assess the change in weekly receipt of four routine adult vaccines by Medicare beneficiaries aged ≥65 during the pandemic: (13-valent pneu­mococcal conjugate vaccine [PCV13], 23-valent pneumococ­cal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]). The comparison periods were Jan. 6–July 20, 2019, and Jan. 5–July 18, 2020.

Of the Medicare enrollees in the study sample, 85% were White, 7% Black, 2% Asian, 2% Hispanic, and 4% other racial and ethnic groups. For each of the four vaccines overall, weekly rates of vaccination declined sharply after the emergency declaration, compared with corresponding weeks in 2019. In the period prior to the emergency declaration (Jan. 5–March 14, 2020), weekly percentages of Medicare beneficiaries vaccinated with PPSV23, Td/Tdap, and RZV were consistently higher than rates during the same period in 2019.

After the March 13 declaration, while weekly vaccination rates plummeted 25% for PPSV23 and 62% for RZV in the first week, the greatest weekly declines were during April 5-11, 2020, for PCV13, PPSV23, and Td/Tdap, and during April 12-18, 2020, for RZV. The pandemic weekly vaccination rate nadirs revealed declines of 88% for PCV13, 80% for PPSV23, 70% for Td/Tdap, and 89% for RZV.
 

Routine vaccinations increased midyear

Vaccination rates recovered gradually. For the most recently assessed pandemic week (July 12-18, 2020), the rate for PPSV23 was 8% higher than in the corresponding period in 2019. Weekly corresponding rates for other examined vaccines, however, remained much lower than in 2019: 44% lower for RZV, 24% lower for Td/Tdap and 43% lower for PCV13. The CDC Advisory Committee on Immunization Practices voted in June 2019 to stop recommending PCV13 for adults aged ≥65 years and so vaccination with PCV13 among this population declined in 2020, compared with that in 2019.

Another significant drop in the rates of adult vaccinations may have occurred because of the surge in COVID-19 infections in the fall of 2020 and subsequent closures and renewal of lockdown in many localities.
 

Disparities in routine vaccination trends

Dr. Hong and colleagues noted that their findings are consistent with prior reports of declines in pediatric vaccine ordering, administration, and coverage during the pandemic. While the reductions were similar across all racial and ethnic groups, the magnitudes of recovery varied, with vaccination rates lower among racial and ethnic minority adults than among White adults.

Physicians are going to have to play catch-up when it comes to getting older patients their routine, but important, vaccinations missed during the pandemic.

©Sean Warren/iStockphoto.com

Weekly general vaccination among Medicare beneficiaries aged ≥ 65 year fell by around 80% soon after the national COVID-19 emergency declaration and have recovered only partially and gradually, according to a report by Kai Hong, PhD, and colleagues at the Centers for Disease Control and Prevention, published in the Morbidity and Mortality Weekly Report. “As the pandemic continues,” the investigators stated, “vaccination providers should continue efforts to resolve disruptions in routine adult vaccination.”

The CDC issued guidance recommending postponement of routine adult vaccination in response to the March 13, 2020, COVID-19 national emergency declaration by the U.S. government and also to state and local shelter-in-place orders. Health care facility operations were restricted because of safety concerns around exposure to the SARS-CoV-2 virus. The result was a significant drop in routine medical care including adult vaccinations.

The investigators examined Medicare enrollment and claims data to assess the change in weekly receipt of four routine adult vaccines by Medicare beneficiaries aged ≥65 during the pandemic: (13-valent pneu­mococcal conjugate vaccine [PCV13], 23-valent pneumococ­cal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]). The comparison periods were Jan. 6–July 20, 2019, and Jan. 5–July 18, 2020.

Of the Medicare enrollees in the study sample, 85% were White, 7% Black, 2% Asian, 2% Hispanic, and 4% other racial and ethnic groups. For each of the four vaccines overall, weekly rates of vaccination declined sharply after the emergency declaration, compared with corresponding weeks in 2019. In the period prior to the emergency declaration (Jan. 5–March 14, 2020), weekly percentages of Medicare beneficiaries vaccinated with PPSV23, Td/Tdap, and RZV were consistently higher than rates during the same period in 2019.

After the March 13 declaration, while weekly vaccination rates plummeted 25% for PPSV23 and 62% for RZV in the first week, the greatest weekly declines were during April 5-11, 2020, for PCV13, PPSV23, and Td/Tdap, and during April 12-18, 2020, for RZV. The pandemic weekly vaccination rate nadirs revealed declines of 88% for PCV13, 80% for PPSV23, 70% for Td/Tdap, and 89% for RZV.
 

Routine vaccinations increased midyear

Vaccination rates recovered gradually. For the most recently assessed pandemic week (July 12-18, 2020), the rate for PPSV23 was 8% higher than in the corresponding period in 2019. Weekly corresponding rates for other examined vaccines, however, remained much lower than in 2019: 44% lower for RZV, 24% lower for Td/Tdap and 43% lower for PCV13. The CDC Advisory Committee on Immunization Practices voted in June 2019 to stop recommending PCV13 for adults aged ≥65 years and so vaccination with PCV13 among this population declined in 2020, compared with that in 2019.

Another significant drop in the rates of adult vaccinations may have occurred because of the surge in COVID-19 infections in the fall of 2020 and subsequent closures and renewal of lockdown in many localities.
 

Disparities in routine vaccination trends

Dr. Hong and colleagues noted that their findings are consistent with prior reports of declines in pediatric vaccine ordering, administration, and coverage during the pandemic. While the reductions were similar across all racial and ethnic groups, the magnitudes of recovery varied, with vaccination rates lower among racial and ethnic minority adults than among White adults.

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

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

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

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

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

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

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

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

A 16-minute podcast from JAMA: The Journal of the American Medical Association that attempts to discuss structural racism in the U.S. health care system has stirred conversation on social media about the handling and promotion of the episode.

Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.

“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.

“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”

Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”

He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”

The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.

B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.

“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said. 

Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.

“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”

Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.

The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.

Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.

“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”

Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.

JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.

AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”

He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”

This article was updated 3/5/21.

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

A 16-minute podcast from JAMA: The Journal of the American Medical Association that attempts to discuss structural racism in the U.S. health care system has stirred conversation on social media about the handling and promotion of the episode.

Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.

“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.

“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”

Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”

He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”

The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.

B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.

“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said. 

Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.

“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”

Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.

The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.

Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.

“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”

Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.

JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.

AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”

He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”

This article was updated 3/5/21.

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

A 16-minute podcast from JAMA: The Journal of the American Medical Association that attempts to discuss structural racism in the U.S. health care system has stirred conversation on social media about the handling and promotion of the episode.

Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.

“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.

“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”

Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”

He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”

The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.

B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.

“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said. 

Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.

“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”

Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.

The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.

Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.

“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”

Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.

JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.

AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”

He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”

This article was updated 3/5/21.

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.

The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
 

‘All carbohydrates are not the same’

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.

Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Dr. Jenkins declared in an interview.
 

New PURE data tip the evidence balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.

Higher BMI associated with greater glycemic index effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.

This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.

PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.

Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

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

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com